Trial Outcomes & Findings for Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases (NCT NCT01004172)

NCT ID: NCT01004172

Last Updated: 2018-12-14

Results Overview

CNS objective response rate is the percentage of participants that achieve CNS complete or partial response as follows: CNS complete response (CR) is achieved if all of the following are satisfied: * Complete resolution of all measurable (\>= 1 cm in longest dimension \[LD\]) and non-measurable brain metastases * No new CNS lesions (defined as any new lesion \>= 6 mm in LD) * Stable or decreasing steroid dose * No new/progressive tumor-related neurologic signs or symptoms * No progression of extra-CNS disease as assessed by RECIST CNS partial response (PR) is achieved if all of the following are satisfied: -\>/= 50% reduction in the volumetric sum of all measurable (\>/= 1 cm in LD) brain metastases compared to baseline * No progression on non-measurable lesions * No new CNS lesions (defined as any new lesion \>/= 6 mm in LD) * Stable or decreasing steroid dose * No new/progressive tumor-related neurologic signs or symptoms * No progression of extra-CNS disease as assessed by RECIST

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 38 participants
• Primary outcome timeframe: Response was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment duration for this study cohort was a median (range) of 8 cycles (1-20) which approximates months given the 4 week cycle length.
• Results posted on: 2018-12-14

Participant Flow

Participants were recruited between November 2009 and August 2012.

Participant milestones

Measure	Carboplatin, Bevacizumab, Trastuzumab (if HER2+) Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab\*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only \*8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2
Overall Study STARTED	38
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	38

Reasons for withdrawal

Measure	Carboplatin, Bevacizumab, Trastuzumab (if HER2+) Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab\*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only \*8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2
Overall Study Progressive Disease in CNS Only	16
Overall Study Progressive Disease in Non-CNS Only	16
Overall Study Progressive Disease in CNS and Non-CNS	2
Overall Study Adverse Event	1
Overall Study Physician Decision	1
Overall Study Symptomatic Deterioration	2

Baseline Characteristics

Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases

Baseline characteristics by cohort

Measure	Carboplatin, Bevacizumab, Trastuzumab (if HER2+) n=38 Participants Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab\*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only \*8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2
Age, Customized	48 years n=5 Participants
Sex: Female, Male Female	38 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized White	34 participants n=5 Participants
Race/Ethnicity, Customized Black or African-American	1 participants n=5 Participants
Race/Ethnicity, Customized Asian	3 participants n=5 Participants
Region of Enrollment United States	38 participants n=5 Participants

PRIMARY outcome

Timeframe: Response was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment duration for this study cohort was a median (range) of 8 cycles (1-20) which approximates months given the 4 week cycle length.

Population: The analysis dataset is comprised of assessable participants. Per protocol, assessable is defined as those who have at least one lesion on baseline MRI with longest with longest diameter \>10 mm on T1-weighted, gadolinium-enhanced. All enrolled participants were assessable.

CNS objective response rate is the percentage of participants that achieve CNS complete or partial response as follows:

CNS complete response (CR) is achieved if all of the following are satisfied:

• Complete resolution of all measurable (>= 1 cm in longest dimension [LD]) and non-measurable brain metastases
• No new CNS lesions (defined as any new lesion >= 6 mm in LD)
• Stable or decreasing steroid dose
• No new/progressive tumor-related neurologic signs or symptoms
• No progression of extra-CNS disease as assessed by RECIST

CNS partial response (PR) is achieved if all of the following are satisfied:

->/= 50% reduction in the volumetric sum of all measurable (>/= 1 cm in LD) brain metastases compared to baseline

• No progression on non-measurable lesions
• No new CNS lesions (defined as any new lesion >/= 6 mm in LD)
• Stable or decreasing steroid dose
• No new/progressive tumor-related neurologic signs or symptoms
• No progression of extra-CNS disease as assessed by RECIST

Outcome measures

Measure

Carboplatin, Bevacizumab, Trastuzumab (if HER2+) n=38 Participants Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab\*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only \*8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2

Central Nervous System (CNS) Objective Response Rate

63 percentage of participants Interval 47.0 to 77.0

SECONDARY outcome

Timeframe: Disease was evaluated radiologically at baseline, cycle 2, cycle 4 and thereafter on treatment every 2 cycles (CNS disease) and every 4 cycles (non-disease). Maximum PFS follow-up for this study cohort was 18.6 months.

Population: The analysis dataset is comprised of all enrolled participants.

Progression-Free Survival (PFS) is defined as the duration of time from start of treatment to time of disease progression (PD), second cancer, or death, whichever occurs first. PD if any of the following occur:

CNS Disease

• >/=40% increase in the volumetric sum of all measurable lesions as compared to the smallest volume on treatment
• Progression of non-measurable lesions
• New lesions (>/=6 mm)

Non-CNS Disease

• RECIST 1.0 criteria: at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded on treatment or the appearance of >/=1 new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

Symptomatic

• Increasing steroid requirement
• Global deterioration of health status requiring discontinuation of treatment
• New/progression tumor-related neurologic signs and symptoms except for transient worsening lasting </=14 days

Outcome measures

Measure

Carboplatin, Bevacizumab, Trastuzumab (if HER2+) n=38 Participants Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab\*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only \*8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2

Progression-Free Survival

5.6 months Interval 4.7 to 6.5

SECONDARY outcome

Timeframe: Response was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment duration for this study cohort was a median (range) of 8 cycles (1-20) which approximates months given the 4 week cycle length.

Population: The analysis dataset is comprised of assessable participants. Per protocol, assessable is defined as those who have at least one lesion on baseline MRI with longest with longest diameter \>10 mm on T1-weighted, gadolinium-enhanced. All enrolled participants were assessable.

CNS best response was defined based on standard criteria. Adding to CR and PR (defined in the primary outcome measure):

CNS stable disease (SD) is achieving all the following:

• < 50% reduction in the volumetric sum of all measurable (>/= 1 cm in LD) brain metastases compared to baseline
• No progression on non-measurable lesions
• No new CNS lesions (defined as any new lesion >/= 6 mm in LD)
• Stable or decreasing steroid dose
• No new/progressive tumor-related neurologic signs or symptoms
• No progression of extra-CNS disease as assessed by RECIST

CNS Progressive Disease (PD) was experiencing any of the following:

->/- 40% increase in the volumetric sum of all measurable (>/= 1 cm in LD) brain metastases compared to baseline

• Progression on non-measurable lesions
• New CNS lesions (defined as any new lesion >/= 6 mm in LD)
• Increasing steroid dose
• New/progressive tumor-related neurologic signs or symptoms
• Progression of extra-CNS disease as assessed by RECIST

Outcome measures

Measure	Carboplatin, Bevacizumab, Trastuzumab (if HER2+) n=38 Participants Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab\*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only \*8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2
CNS Best Response Complete Response	0 Participants
CNS Best Response Partial Response	24 Participants
CNS Best Response Stable Disease >/=24 weeks	2 Participants
CNS Best Response Stable Disease < 24 weeks	5 Participants
CNS Best Response Progressive Disease	7 Participants

SECONDARY outcome

Timeframe: Disease was evaluated radiologically at baseline, cycle 2, cycle 4 and thereafter on treatment every 2 cycles (CNS disease) and every 4 cycles (non-disease). Maximum progression follow-up for this study cohort was 18.6 months.

Population: The analysis dataset is comprised of all enrolled participants.

Site of first progression is classified as follows:

CNS Disease

• >/=40% increase in the volumetric sum of all measurable lesions as compared to the smallest volume on treatment
• Progression of non-measurable lesions
• New lesions (>/=6 mm) Non-CNS Disease
• Per RECIST 1.0 criteria: PD is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

Symptomatic

• Increasing steroid requirement
• Global deterioration of health status requiring discontinuation of treatment
• New/progression tumor-related neurologic signs and symptoms (NSS) except for transient worsening lasting </=14 days

Outcome measures

Measure	Carboplatin, Bevacizumab, Trastuzumab (if HER2+) n=38 Participants Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab\*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only \*8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2
Site of First Progression CNS	15 participants
Site of First Progression Non-CNS	12 participants
Site of First Progression Both CNS and Non-CNS	6 participants
Site of First Progression Symptomatic	2 participants
Site of First Progression No Site	3 participants

SECONDARY outcome

Timeframe: Maximum survival follow-up for the study cohort was 66 months.

Population: The analysis dataset is comprised of enrolled patients.

Participants were assessed every 6 months post-treatment. Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.

Outcome measures

Measure

Carboplatin, Bevacizumab, Trastuzumab (if HER2+) n=38 Participants Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab\*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only \*8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2

Overall Survival

14 months Interval 11.7 to 20.7

Adverse Events

Carboplatin, Bevacizumab, Trastuzumab (if HER2+)

Serious events: 16 serious events

Other events: 38 other events

Deaths: 38 deaths

Serious adverse events

Measure	Carboplatin, Bevacizumab, Trastuzumab (if HER2+) n=38 participants at risk Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab\*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only \*8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2
Blood and lymphatic system disorders Hemoglobin	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Eye disorders Ocular-other	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
General disorders Fatigue	15.8% 6/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations Leukocytes	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations Neutrophils	7.9% 3/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations Platelets	10.5% 4/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations ALT, SGPT	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations AST, SGOT	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypercalcemia	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyponatremia	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Nonneuropathic generalized weakness	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Joint, pain	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Bronchospasm, wheezing	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Vascular disorders Hypertension	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Vascular disorders Thrombosis/thrombus/embolism	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.

Other adverse events

Measure	Carboplatin, Bevacizumab, Trastuzumab (if HER2+) n=38 participants at risk Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab\*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only \*8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2
Gastrointestinal disorders Abdomen, hemorrhage NOS	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Abdomen, pain	7.9% 3/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations Alkaline phosphatase	34.2% 13/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Immune system disorders Allergic reaction	13.2% 5/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	7.9% 3/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Alopecia	13.2% 5/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations ALT, SGPT	36.8% 14/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Anorexia	21.1% 8/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Anxiety	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations AST, SGOT	60.5% 23/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Ataxia	7.9% 3/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Back, pain	15.8% 6/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Bone, pain	15.8% 6/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Brachial plexopathy	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Reproductive system and breast disorders Breast, pain	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Injury, poisoning and procedural complications Bruising	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Buttock, pain	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Cardiac disorders Cardiac-other	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Chest wall, pain	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
General disorders Chest/thoracic pain NOS	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders CNS cerebrovascular ischemia	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders CNS, hemorrhage	10.5% 4/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Cognitive disturbance	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Colon, hemorrhage	7.9% 3/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Confusion	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Constipation	36.8% 14/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
General disorders Constitutional, other	13.2% 5/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Cough	26.3% 10/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations Creatinine	10.5% 4/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Endocrine disorders Cushingnoid appearance	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Renal and urinary disorders Cystitis	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Dehydration	7.9% 3/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Dental/teeth/peridontal, pain	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Depression	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Diarrhea w/o prior colostomy	28.9% 11/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Dizziness	18.4% 7/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Eye disorders Double vision	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Dry skin	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Dyspepsia	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Dyspnea	7.9% 3/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
General disorders Edema head and neck	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Esophagitis	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Extremity-limb, pain	18.4% 7/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
General disorders Extremity-lower (gait/walking)	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
General disorders Fatigue	71.1% 27/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Febrile neutropenia	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
General disorders Fever w/o neutropenia	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Flatulence	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Vascular disorders Flushing	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders GI-other	10.5% 4/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Hand-foot reaction	7.9% 3/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Head/headache	52.6% 20/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Hemoglobin	76.3% 29/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Vascular disorders Hot flashes	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Hydrocephalus	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypercalcemia	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations Hypercholesterolemia	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyperglycemia	47.4% 18/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypernatremia	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Vascular disorders Hypertension	23.7% 9/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypoalbuminemia	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypocalcemia	13.2% 5/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypoglycemia	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypokalemia	10.5% 4/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypomagnesemia	7.9% 3/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyponatremia	15.8% 6/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Renal and urinary disorders Incontinence urinary	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Infections and infestations Infection Gr0-2 neut, dental-tooth	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Infections and infestations Infection Gr0-2 neut, sinus	7.9% 3/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Infections and infestations Infection Gr0-2 neut, upper airway	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Infections and infestations Infection Gr0-2 neut, urinary tract	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Infections and infestations Infection w/ unk ANC sinus	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Infections and infestations Infection-other	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations INR	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Insomnia	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Jejunum, hemorrhage	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Joint, pain	15.8% 6/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Laryngeal nerve dysfunction	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Larynx, pain	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Cardiac disorders Left ventricular systolic dysfunction	13.2% 5/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations Leukocytes	52.6% 20/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Lung, hemorrhage	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations Lymphopenia	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Memory impairment	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Mental status	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations Metabolic/Laboratory-other	10.5% 4/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Muco/stomatitis (symptom) oral cavity	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Muco/stomatitis by exam, oral cavity	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Musculoskeletal/soft tissue-other	7.9% 3/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Nail changes	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Nasal cavity/paranasal sinus reaction	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Nausea	44.7% 17/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Neck, pain	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Neurologic-other	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Eye disorders Neuropathy CN II vision	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Neuropathy-motor	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Neuropathy-sensory	36.8% 14/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations Neutrophils	52.6% 20/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Nonneuropathic generalized weakness	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Nonneuropathic lower extr muscle weak	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Nonneuropathic right-side muscle weak	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Nose, hemorrhage	31.6% 12/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Eye disorders Ocular-other	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Oral cavity, hemorrhage	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
General disorders Pain-other	13.2% 5/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Cardiac disorders Palpitations	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Vascular disorders Peripheral arterial ischemia	7.9% 3/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Vascular disorders Phlebitis	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations Platelets	71.1% 27/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Renal and urinary disorders Proteinuria	21.1% 8/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Pruritus/itching	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Investigations PTT	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory-other	7.9% 3/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Rash/desquamation	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Rash: acne/acneiform	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Rectum, hemorrhage	15.8% 6/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
General disorders Rigors/chills	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Scalp, pain	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Seizure	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Sinus, pain	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Skin, pain	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Skin-other	10.5% 4/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Speech impairment	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Stomach, pain	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Sweating	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Syncope	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Taste disturbance	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Eye disorders Tearing	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Throat/pharynx/larynx, pain	10.5% 4/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Vascular disorders Thrombosis/thrombus/embolism	7.9% 3/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Tremor	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Ulceration	2.6% 1/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Reproductive system and breast disorders Vaginal dryness	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Vascular disorders Visceral arterial ischemia	7.9% 3/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Eye disorders Vision-blurred	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Voice changes/dysarthria	5.3% 2/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Vomiting	15.8% 6/38 • Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.

Additional Information

Nancy Lin, MD

Dana-Farber Cancer Institure

Phone: 617.632.2335

Email: nlin@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place