Trial Outcomes & Findings for Abiraterone Acetate Combined With Dutasteride for Metastatic Castrate Resistant Prostate Cancer (NCT NCT01393730)

NCT ID: NCT01393730

Last Updated: 2018-03-15

Results Overview

AR related mutation was defined as presence of T878A mutation. Expression of T878A was measured by established methods.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 40 participants
• Primary outcome timeframe: Pairs of patients samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.
• Results posted on: 2018-03-15

Participant Flow

Patients enrolled from September 2011 through October 2012

Participant milestones

Measure	Abiraterone + Prednisone + Dutasteride Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Overall Study STARTED	40
Overall Study Treated	38
Overall Study Evaluable AR Amplification	21
Overall Study Evaluable AR Mutation	14
Overall Study COMPLETED	34
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Measure	Abiraterone + Prednisone + Dutasteride Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Overall Study Withdrawal by Subject	3
Overall Study Other	2
Overall Study Adverse Event	1

Baseline Characteristics

Abiraterone Acetate Combined With Dutasteride for Metastatic Castrate Resistant Prostate Cancer

Baseline characteristics by cohort

Measure	Abiraterone + Prednisone + Dutasteride n=40 Participants Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Age, Continuous	61 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants
Region of Enrollment United States	40 participants n=5 Participants

PRIMARY outcome

Timeframe: Pairs of patients samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.

Population: The analysis dataset is comprised of all patients evaluable for AR mutation.

AR related mutation was defined as presence of T878A mutation. Expression of T878A was measured by established methods.

Outcome measures

Measure	Abiraterone + Prednisone + Dutasteride n=14 Participants Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Number of Participants With Androgen Receptor (AR) Related Mutations	1 Participants

SECONDARY outcome

Timeframe: Samples for testosterone analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.

Population: The analysis dataset is comprised of all treated patients.

Serum testosterone levels were estimated based on established methods. The change from baseline to progression was calculated for each participant.

Outcome measures

Measure	Abiraterone + Prednisone + Dutasteride n=38 Participants Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Change in Serum Levels of Testosterone	0.25 ng/dL Interval 0.1 to 0.5

SECONDARY outcome

Timeframe: PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.

Population: The analysis dataset is comprised of all treated patients.

PSA response was defined as decline of 50% from baseline confirmed by a PSA at least 4 weeks later based on Prostate-specific Antigen Working Group-2 (PSAWG-2) (2008) criteria.

Outcome measures

Measure	Abiraterone + Prednisone + Dutasteride n=38 Participants Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Prostate-Specific Antigen (PSA) Response	34 Participants

SECONDARY outcome

Timeframe: PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.

Population: The analysis dataset is comprised of all treated patients.

Time to PSA progression based on the Kaplan-Meier method was defined as the time between registration and documented PSA progression. PSA progression based on Prostate-Specific Antigen Working Group-2 (PSAWG-2) (2008) criteria was an increase of >/=25% and >/= 2 ng/ml after 12 weeks for patients without a PSA decline from baseline and an increase of >/=25% and >/= 2 ng/ml above the nadir, confirmed by a 2nd value 3 weeks or later for patients with a PSA decline from baseline. PSA progression was reported not duration of response.

Outcome measures

Measure	Abiraterone + Prednisone + Dutasteride n=38 Participants Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Time to PSA Progression	5 months Interval 3.0 to 8.0

SECONDARY outcome

Timeframe: Disease was evaluated radiologically at baseline and every 12 weeks cycles on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.

Population: The analysis dataset is comprised of all treated patients.

Overall response (OR) rate was defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Outcome measures

Measure	Abiraterone + Prednisone + Dutasteride n=38 Participants Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Best Overall Response	6 Participants

SECONDARY outcome

Timeframe: Disease evaluation occurred every 12 weeks while patients were receiving treatment. In this study cohort, participants were followed up to 48 months for this endpoint.

Population: The analysis dataset is comprised of all treated patients.

TTP based on the Kaplan-Meier method is defined as the duration of time from study entry to documented first observation of progressive disease (PD). Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Outcome measures

Measure	Abiraterone + Prednisone + Dutasteride n=38 Participants Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Time to Progression (TTP)	11 Months Interval 8.0 to 15.0

SECONDARY outcome

Timeframe: Patients' samples were evaluated at baseline and every 12 weeks on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.

Population: The analysis dataset is comprised of all evaluable patients.

Presence of AR amplification was measured by established methods.

Outcome measures

Measure	Abiraterone + Prednisone + Dutasteride n=21 Participants Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Presence of AR Amplification	10 Participants

SECONDARY outcome

Timeframe: Pairs of patients' samples for androgen analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.

Population: The analysis dataset is comprised of all treated patients.

Serum androgen levels measured based on established methods. The change from baseline to progression was calculated for each participant.

Outcome measures

Measure	Abiraterone + Prednisone + Dutasteride n=38 Participants Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Change in Serum Androgen Levels	1.2 ng/dl Interval 0.7 to 2.0

SECONDARY outcome

Timeframe: Pairs of patients' samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.

Population: Data were not collected for this secondary endpoint.

CTCs were measured based on established methods.

Outcome measures

Outcome data not reported

Adverse Events

Abiraterone + Prednisone + Dutasteride

Serious events: 12 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Measure	Abiraterone + Prednisone + Dutasteride n=38 participants at risk Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Investigations Alanine aminotransferase increased	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Investigations Lipase increased	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Cardiac disorders Conduction abnormality/Atrioventricular heart block - AV block-second degree Mobitz Type II	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Cardiac disorders Cardiac disorders - Other, specify	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Infections and infestations Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Ureter	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Infections and infestations Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Vagina	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Injury, poisoning and procedural complications Thrombosis/embolism (vascular access-related)	13.2% 5/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Injury, poisoning and procedural complications Thromboembolic event	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Investigations Lipase	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Bone: spine-scoliosis	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Nervous system disorders "Neuropathy: cranial - CN III Pupil, upper eyelid, extra ocular movements"	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.

Other adverse events

Measure	Abiraterone + Prednisone + Dutasteride n=38 participants at risk Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression Abiraterone acetate: 1000 mg orally, once per day Dutasteride: 3.5 mg orally once per day Prednisone: 5 mg orally once per day
Blood and lymphatic system disorders Bone marrow cellularity	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Blood and lymphatic system disorders Lymphopenia	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Blood and lymphatic system disorders Blood/Bone Marrow-Other (Specify)	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Cardiac disorders Conduction abnormality/Atrioventricular heart block - Wolff-Parkinson-White syndrome	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Cardiac disorders Palpitations	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Cardiac disorders Cardiac disorders - Other, specify	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Congenital, familial and genetic disorders Congenital, familial and genetic disorders	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Ear and labyrinth disorders External ear pain	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Ear and labyrinth disorders Tinnitus	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Ear and labyrinth disorders Ear and labyrinth disorders	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Eye disorders Cataract	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Eye disorders Eye disorders - Other, specify	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Gastrointestinal disorders Abdominal pain	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Gastrointestinal disorders "Fistula, GI - Anus"	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Gastrointestinal disorders "Fistula, GI - Esophagus"	18.4% 7/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Gastrointestinal disorders "Fistula, GI - Ileum"	10.5% 4/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Gastrointestinal disorders "Fistula, GI - Jejunum"	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Gastrointestinal disorders "Fistula, GI - Stomach"	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Gastrointestinal disorders Nausea	15.8% 6/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Gastrointestinal disorders "Obstruction, GI - Esophagus"	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Gastrointestinal disorders "Stricture/stenosis (including anastomotic), GI - Duodenum"	13.2% 5/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
General disorders "Fatigue (asthenia, lethargy, malaise)"	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
General disorders Obesity	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
General disorders Sweating (diaphoresis)	57.9% 22/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
General disorders Weight gain	7.9% 3/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
General disorders Weight loss	7.9% 3/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
General disorders Localized edema	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
General disorders Non-cardiac chest pain	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
General disorders Pain	21.1% 8/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
General disorders General disorders and administration site conditions - Other, specify	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Infections and infestations Infection (documented clinically/microbiologically) w/Grade 3/4 neutrophils -Brain	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Infections and infestations Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Liver	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Infections and infestations Infection (documented clinically or microbiologically) w/Grade 3 or 4 neutrophils -Nerve-peripheral	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Infections and infestations Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Peristomal	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Infections and infestations Skin infection	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Infections and infestations Infection (documented clinically/microbiologically) w/Grade 3/4 neutrophils -Upper aerodigestive NOS	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Infections and infestations Urinary tract infection	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Injury, poisoning and procedural complications Bruising	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Injury, poisoning and procedural complications Fracture	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Investigations Alanine aminotransferase increased	18.4% 7/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Investigations Alkaline phosphatase increased	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Investigations Aspartate aminotransferase increased	21.1% 8/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Investigations Blood bilirubin increased	10.5% 4/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Metabolism and nutrition disorders Anorexia	7.9% 3/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Metabolism and nutrition disorders "Bicarbonate, serum-low"	15.8% 6/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Metabolism and nutrition disorders Hypocalcemia	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Metabolism and nutrition disorders "Glucose, serum-high (hyperglycemia)"	31.6% 12/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Bone: spine-scoliosis	7.9% 3/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Extremity-lower (gait/walking)	18.4% 7/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Extremity-upper (function)	13.2% 5/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Fibrosis-cosmesis	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Fracture	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Local complication - device/prosthesis-related	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders "Muscle weakness, generalized or specific area (not due to neuropathy) - Extremity-upper"	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Osteoporosis	10.5% 4/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Soft tissue necrosis - Abdomen	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Soft tissue necrosis - Head	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Soft tissue necrosis - Neck	10.5% 4/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Musculoskeletal and connective tissue disorders Musculoskeletal/Soft Tissue-Other (Specify)	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Nervous system disorders Irritability (children <3 years of age)	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Nervous system disorders "Leak, cerebrospinal fluid (CSF)"	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Nervous system disorders "Neuropathy: cranial - CN III Pupil, upper eyelid, extra ocular movements"	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Nervous system disorders Nervous system disorders	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Nervous system disorders Nervous system disorders - Other, specify	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Psychiatric disorders Insomnia	10.5% 4/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Psychiatric disorders Psychiatric disorders	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Renal and urinary disorders "Leak (including anastomotic), GU - Kidney"	10.5% 4/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Renal and urinary disorders "Leak (including anastomotic), GU - Spermatic cord"	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Renal and urinary disorders "Leak (including anastomotic), GU - Ureter"	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Renal and urinary disorders Renal and urinary disorders - Other, specify	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Reproductive system and breast disorders Gynecomastia	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Reproductive system and breast disorders Testicular pain	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Respiratory, thoracic and mediastinal disorders Atelectasis	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Respiratory, thoracic and mediastinal disorders Cough	7.9% 3/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Respiratory, thoracic and mediastinal disorders Dyspnea	7.9% 3/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Respiratory, thoracic and mediastinal disorders Laryngeal fistula	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Respiratory, thoracic and mediastinal disorders Prolonged intubation after pulmonary resection (>24 hrs after surgery)	7.9% 3/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Skin and subcutaneous tissue disorders Burn	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Skin and subcutaneous tissue disorders Hyperpigmentation	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Skin and subcutaneous tissue disorders Nail changes	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Skin and subcutaneous tissue disorders Rash: dermatitis associated with radiation - Chemoradiation	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Skin and subcutaneous tissue disorders Skin breakdown/decubitus ulcer	7.9% 3/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Skin and subcutaneous tissue disorders Striae	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Skin and subcutaneous tissue disorders Ulceration	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Skin and subcutaneous tissue disorders Dermatology/Skin-Other (Specify)	10.5% 4/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Surgical and medical procedures Intra-operative injury - Pharynx	2.6% 1/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Vascular disorders Phlebitis (including superficial thrombosis)	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Vascular disorders Portal vein flow	26.3% 10/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Vascular disorders Thrombosis/embolism (vascular access-related)	39.5% 15/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.
Vascular disorders Thrombosis/thrombus/embolism	5.3% 2/38 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint. Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other' events have no further specification.

Additional Information

Dr. Mary-Ellen Taplin

Dana-Farber Cancer Institute

Phone: 617-582-7221

Email: mary_taplin@dfci.harvard.edu

Results disclosure agreements

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