Trial Outcomes & Findings for Ph II Gemcitabine, Erlotinib, and Gemcitabine With Erlotinib/Elderly Patients W/ IIIB/IV NSCLC (NCT NCT00283244)

Last Updated: 2017-04-24

Results Overview

We would consider the combination of gemcitabine plus erlotinib or single agent erlotinib to be worthy of further study if there was an increased progressed-free survival. We would use an increase to 45% progression-free survival at 6 months as significant. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

147 participants

Primary outcome timeframe

Six months

Results posted on

2017-04-24

Participant Flow

Subjects were recruited for this study between March 2006 and May 2010

Of the 160 patients who signed informed consent, 13 didn't start treatment for the following reasons: withdrew informed consent (5), referred to hospice (4), ineligible (3), and death before treatment (1). A patient received treatment on trial, but was determined to be ineligible due to incorrect diagnosis, and was thus not included in results.

Participant milestones

Participant milestones
Measure	Arm A (Gemcitabine) Patients receive gemcitabine hydrochloride 1200mg/m2 IV on days 1 and 8. Patients with progressive disease may cross over to arm B.	Arm B (Erlotinib) Patients receive oral erlotinib hydrochloride 150mg p.o. daily on days 1-21.	Arm C (Gemcitabine + Erlotinib) Patients receive gemcitabine hydrochloride 1000mg/m2 IV on days 1 and 8 and erlotinib hydrochloride 100mg p.o. daily
Overall Study STARTED	44	51	51
Overall Study COMPLETED	26	0	0
Overall Study NOT COMPLETED	18	51	51

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (Gemcitabine) Patients receive gemcitabine hydrochloride 1200mg/m2 IV on days 1 and 8. Patients with progressive disease may cross over to arm B.	Arm B (Erlotinib) Patients receive oral erlotinib hydrochloride 150mg p.o. daily on days 1-21.	Arm C (Gemcitabine + Erlotinib) Patients receive gemcitabine hydrochloride 1000mg/m2 IV on days 1 and 8 and erlotinib hydrochloride 100mg p.o. daily
Overall Study Adverse Event	0	8	11
Overall Study Death	4	3	2
Overall Study Lack of Efficacy	8	32	26
Overall Study Withdrawal by Subject	1	2	2
Overall Study Physician Decision	0	0	1
Overall Study Medical illness (other complicating dz)	4	3	6
Overall Study Clinical deterioration	1	3	3

Baseline Characteristics

Ph II Gemcitabine, Erlotinib, and Gemcitabine With Erlotinib/Elderly Patients W/ IIIB/IV NSCLC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Gemcitabine) n=44 Participants Patients receive gemcitabine hydrochloride 1200mg/m2 IV on days 1 and 8. Patients with progressive disease may cross over to arm B.	Arm B (Erlotinib) n=51 Participants Patients receive oral erlotinib hydrochloride 150mg p.o. daily on days 1-21.	Arm C (Gemcitabine + Erlotinib) n=51 Participants Patients receive gemcitabine hydrochloride 1000mg/m2 IV on days 1 and 8 and erlotinib hydrochloride 100mg p.o. daily	Total n=146 Participants Total of all reporting groups
Age, Continuous	74 years n=5 Participants	76 years n=7 Participants	78 years n=5 Participants	76 years n=4 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	27 Participants n=7 Participants	24 Participants n=5 Participants	73 Participants n=4 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	24 Participants n=7 Participants	27 Participants n=5 Participants	73 Participants n=4 Participants
Region of Enrollment United States	44 participants n=5 Participants	51 participants n=7 Participants	51 participants n=5 Participants	146 participants n=4 Participants
Cancer Stage (TNM) IIIB (Any T, N3, M0 or T4, N2, M0)	11 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants	26 participants n=4 Participants
Cancer Stage (TNM) IV (Any T, any N, M1a or M1b)	33 participants n=5 Participants	46 participants n=7 Participants	41 participants n=5 Participants	120 participants n=4 Participants
ECOG Performance Status 0	10 participants n=5 Participants	7 participants n=7 Participants	6 participants n=5 Participants	23 participants n=4 Participants
ECOG Performance Status 1	21 participants n=5 Participants	29 participants n=7 Participants	29 participants n=5 Participants	79 participants n=4 Participants
ECOG Performance Status 2	13 participants n=5 Participants	14 participants n=7 Participants	14 participants n=5 Participants	41 participants n=4 Participants
ECOG Performance Status Missing at baseline	0 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants
Smoking history Never or light smoker	4 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	15 participants n=4 Participants
Smoking history Current or former smoker	35 participants n=5 Participants	43 participants n=7 Participants	42 participants n=5 Participants	120 participants n=4 Participants
Smoking history Missing	5 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants	11 participants n=4 Participants
Histology Adenocarcinoma	28 participants n=5 Participants	34 participants n=7 Participants	31 participants n=5 Participants	93 participants n=4 Participants
Histology Squamous	7 participants n=5 Participants	5 participants n=7 Participants	8 participants n=5 Participants	20 participants n=4 Participants
Histology Large cell carcinoma	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Histology Not otherwise specified	8 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants	32 participants n=4 Participants
Cumulative Illness Rating scale for Geriatrics (CIRS-G)	11.5 units on a scale n=5 Participants	10 units on a scale n=7 Participants	11 units on a scale n=5 Participants	11 units on a scale n=4 Participants

PRIMARY outcome

Timeframe: Six months

Outcome measures

Outcome measures
Measure	Arm A (Gemcitabine) n=44 Participants Patients receive gemcitabine hydrochloride 1200mg/m2 IV on days 1 and 8. Patients with progressive disease may cross over to arm B.	Arm B (Erlotinib) n=51 Participants Patients receive oral erlotinib hydrochloride 150mg p.o. daily on days 1-21	Arm C (Gemcitabine + Erlotinib) n=51 Participants Patients receive gemcitabine hydrochloride 1000mg/m2 IV on days 1 and 8 and erlotinib hydrochloride 100mg p.o. daily
Progression-free Survival	3.7 months Interval 2.3 to 4.7	2.8 months Interval 1.4 to 3.4	4.1 months Interval 2.4 to 5.0

SECONDARY outcome

Timeframe: Six months

The best overall response (BOR) is the best response recorded from the start of the treatment until disease progression-recurrence (taking as reference for progressive disease the smallest measurement recorded since the treatment started. The response rate was defined as the percentage of patients achieving a BOR of complete response or partial response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Arm A (Gemcitabine) n=44 Participants Patients receive gemcitabine hydrochloride 1200mg/m2 IV on days 1 and 8. Patients with progressive disease may cross over to arm B.	Arm B (Erlotinib) n=51 Participants Patients receive oral erlotinib hydrochloride 150mg p.o. daily on days 1-21	Arm C (Gemcitabine + Erlotinib) n=51 Participants Patients receive gemcitabine hydrochloride 1000mg/m2 IV on days 1 and 8 and erlotinib hydrochloride 100mg p.o. daily
Response Rate	7 percentage of participants	0 percentage of participants	21 percentage of participants

SECONDARY outcome

Timeframe: Up to 3 years

Survival calculated from start of treatment to death from any cause for up to three years.

Outcome measures

Outcome measures
Measure	Arm A (Gemcitabine) n=44 Participants Patients receive gemcitabine hydrochloride 1200mg/m2 IV on days 1 and 8. Patients with progressive disease may cross over to arm B.	Arm B (Erlotinib) n=51 Participants Patients receive oral erlotinib hydrochloride 150mg p.o. daily on days 1-21	Arm C (Gemcitabine + Erlotinib) n=51 Participants Patients receive gemcitabine hydrochloride 1000mg/m2 IV on days 1 and 8 and erlotinib hydrochloride 100mg p.o. daily
Overall Survival	6.8 Months Interval 4.8 to 8.5	5.8 Months Interval 3.0 to 8.3	5.6 Months Interval 3.5 to 8.4

SECONDARY outcome

Timeframe: After each cycle/3 weeks, up to 3 years

Assessments for treatment toxicity will be done with each cycle according to CTCAE v3. Results listed here are grade \>=3, treatment related hematologic events (all) and Grade\>=3 treatment related non hematologic events that occurred in \>=5% of patients in any arm. Adverse events (toxicities) are graded on a 5 point scale from 1 (mild) to 5 (lethal), with grades 3 and higher being severe or life threatening.

Outcome measures

Outcome measures
Measure	Arm A (Gemcitabine) n=44 Participants Patients receive gemcitabine hydrochloride 1200mg/m2 IV on days 1 and 8. Patients with progressive disease may cross over to arm B.	Arm B (Erlotinib) n=51 Participants Patients receive oral erlotinib hydrochloride 150mg p.o. daily on days 1-21	Arm C (Gemcitabine + Erlotinib) n=51 Participants Patients receive gemcitabine hydrochloride 1000mg/m2 IV on days 1 and 8 and erlotinib hydrochloride 100mg p.o. daily
Toxicity Anemia (Grade>=3; treatment related)	1 participants	0 participants	4 participants
Toxicity Neutropenia (Grade>=3; treatment related)	4 participants	1 participants	1 participants
Toxicity Thrombocyopenia (Grade>=3; treatment related)	3 participants	1 participants	2 participants
Toxicity Dehydration (Grade>=3; treatment related)	0 participants	3 participants	2 participants
Toxicity Diarrhea (Grade>=3; treatment related)	0 participants	3 participants	3 participants
Toxicity Dyspnea (Grade>=3; treatment related)	2 participants	0 participants	3 participants
Toxicity Fatigue (Grade>=3; treatment related)	4 participants	1 participants	5 participants
Toxicity Rash (Grade>=3; treatment related)	1 participants	2 participants	3 participants

SECONDARY outcome

Timeframe: After each cycle/3 weeks

The FACT-L is the FACT-G and a lung cancer specific (LCS) subscale given at baseline, after each cycle and at end of treatment. The FACT-G is a 27 item measure of general QOL assessing function in 4 domains: physical well-being (PWB), social-family well-being (SFWB), emotional well-being (EWB) and functional well-being (FWB). Items are rated by patients on a Likert scale from 0 to 4. Higher scores represent better QOL. The TOI-L sums the PWB, FWB, and LCS subscale scores. A best response for TOI-L scores is based on change from baseline and coded as: a change \>=+6 "improved", \<= -6 "worsened" and otherwise "no change". A best overall score response is coded as: Improved (2 visit resp. of "improved" a min. of 28 days apart w/ no interim "worsened") No change (not "improved;" 2 visit resp. of "no change" or "improved" a min. of 28 days apart w/ no interim "worsened") Worsened (not "improved" or "no change;" 2 consecutive "worsened") Other (none of the above)

Outcome measures

Outcome measures
Measure	Arm A (Gemcitabine) n=44 Participants Patients receive gemcitabine hydrochloride 1200mg/m2 IV on days 1 and 8. Patients with progressive disease may cross over to arm B.	Arm B (Erlotinib) n=51 Participants Patients receive oral erlotinib hydrochloride 150mg p.o. daily on days 1-21	Arm C (Gemcitabine + Erlotinib) n=51 Participants Patients receive gemcitabine hydrochloride 1000mg/m2 IV on days 1 and 8 and erlotinib hydrochloride 100mg p.o. daily
Quality of Life (QOL)- Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) Trial Outcome Index-L (TOI-L) Improved	5 participants	6 participants	7 participants
Quality of Life (QOL)- Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) Trial Outcome Index-L (TOI-L) No change	12 participants	9 participants	9 participants
Quality of Life (QOL)- Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) Trial Outcome Index-L (TOI-L) Worsened	11 participants	12 participants	9 participants
Quality of Life (QOL)- Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) Trial Outcome Index-L (TOI-L) Other	16 participants	24 participants	26 participants

Adverse Events

Arm A (Gemcitabine)

Serious events: 16 serious events

Other events: 40 other events

Deaths: 1 deaths

Arm B (Erlotinib)

Serious events: 17 serious events

Other events: 46 other events

Deaths: 3 deaths

Arm C (Gemcitabine + Erlotinib)

Serious events: 26 serious events

Other events: 48 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Robin V. Johnson

UNC Lineberger Comprehensive Cancer Center

Phone: 919-966-1125

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Arm A (Gemcitabine) n=44 participants at risk Patients receive gemcitabine hydrochloride 1200mg/m2 IV on days 1 and 8. Patients with progressive disease may cross over to arm B.	Arm B (Erlotinib) n=51 participants at risk Patients receive oral erlotinib hydrochloride 150mg p.o. daily on days 1-21.	Arm C (Gemcitabine + Erlotinib) n=51 participants at risk Patients receive gemcitabine hydrochloride 1000mg/m2 IV on days 1 and 8 and erlotinib hydrochloride 100mg p.o. daily
Metabolism and nutrition disorders Albumin, Serum-Low (Hypoalbuminemia)	4.5% 2/44 • Number of events 2 • Adverse events were followed for 30 days after cessation of treatment	2.0% 1/51 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment	5.9% 3/51 • Number of events 10 • Adverse events were followed for 30 days after cessation of treatment
Immune system disorders Allergic Reaction/Hypersensitivity (Including Drug Fever)	4.5% 2/44 • Number of events 2 • Adverse events were followed for 30 days after cessation of treatment	2.0% 1/51 • Number of events 1 • Adverse events were followed for 30 days after cessation of treatment	0.00% 0/51 • Adverse events were followed for 30 days after cessation of treatment
Investigations Alt, Sgpt (Serum Glutamic Pyruvic Transaminase)	0.00% 0/44 • Adverse events were followed for 30 days after cessation of treatment	0.00% 0/51 • Adverse events were followed for 30 days after cessation of treatment	5.9% 3/51 • Number of events 4 • Adverse events were followed for 30 days after cessation of treatment
Metabolism and nutrition disorders Anorexia	29.5% 13/44 • Number of events 17 • Adverse events were followed for 30 days after cessation of treatment	25.5% 13/51 • Number of events 15 • Adverse events were followed for 30 days after cessation of treatment	31.4% 16/51 • Number of events 25 • Adverse events were followed for 30 days after cessation of treatment
Investigations Bilirubin (Hyperbilirubinemia)	0.00% 0/44 • Adverse events were followed for 30 days after cessation of treatment	3.9% 2/51 • Number of events 4 • Adverse events were followed for 30 days after cessation of treatment	7.8% 4/51 • Number of events 6 • Adverse events were followed for 30 days after cessation of treatment
Eye disorders Cataract	4.5% 2/44 • Number of events 2 • Adverse events were followed for 30 days after cessation of treatment	0.00% 0/51 • Adverse events were followed for 30 days after cessation of treatment	0.00% 0/51 • Adverse events were followed for 30 days after cessation of treatment
Psychiatric disorders Confusion	6.8% 3/44 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment	5.9% 3/51 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment	0.00% 0/51 • Adverse events were followed for 30 days after cessation of treatment
Gastrointestinal disorders Constipation	29.5% 13/44 • Number of events 16 • Adverse events were followed for 30 days after cessation of treatment	15.7% 8/51 • Number of events 9 • Adverse events were followed for 30 days after cessation of treatment	29.4% 15/51 • Number of events 23 • Adverse events were followed for 30 days after cessation of treatment
Respiratory, thoracic and mediastinal disorders Cough	31.8% 14/44 • Number of events 31 • Adverse events were followed for 30 days after cessation of treatment	19.6% 10/51 • Number of events 11 • Adverse events were followed for 30 days after cessation of treatment	9.8% 5/51 • Number of events 11 • Adverse events were followed for 30 days after cessation of treatment
Investigations Creatinine	2.3% 1/44 • Number of events 1 • Adverse events were followed for 30 days after cessation of treatment	5.9% 3/51 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment	9.8% 5/51 • Number of events 7 • Adverse events were followed for 30 days after cessation of treatment
Metabolism and nutrition disorders Dehydration	4.5% 2/44 • Number of events 2 • Adverse events were followed for 30 days after cessation of treatment	7.8% 4/51 • Number of events 5 • Adverse events were followed for 30 days after cessation of treatment	11.8% 6/51 • Number of events 7 • Adverse events were followed for 30 days after cessation of treatment
Gastrointestinal disorders Diarrhea	22.7% 10/44 • Number of events 17 • Adverse events were followed for 30 days after cessation of treatment	51.0% 26/51 • Number of events 47 • Adverse events were followed for 30 days after cessation of treatment	43.1% 22/51 • Number of events 37 • Adverse events were followed for 30 days after cessation of treatment
Nervous system disorders Dizziness	22.7% 10/44 • Number of events 23 • Adverse events were followed for 30 days after cessation of treatment	9.8% 5/51 • Number of events 7 • Adverse events were followed for 30 days after cessation of treatment	11.8% 6/51 • Number of events 7 • Adverse events were followed for 30 days after cessation of treatment
Skin and subcutaneous tissue disorders Dry Skin	6.8% 3/44 • Number of events 5 • Adverse events were followed for 30 days after cessation of treatment	11.8% 6/51 • Number of events 6 • Adverse events were followed for 30 days after cessation of treatment	5.9% 3/51 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment
Respiratory, thoracic and mediastinal disorders Dyspnea (Shortness Of Breath)	38.6% 17/44 • Number of events 32 • Adverse events were followed for 30 days after cessation of treatment	21.6% 11/51 • Number of events 13 • Adverse events were followed for 30 days after cessation of treatment	29.4% 15/51 • Number of events 30 • Adverse events were followed for 30 days after cessation of treatment
General disorders Edema: Limb	9.1% 4/44 • Number of events 4 • Adverse events were followed for 30 days after cessation of treatment	15.7% 8/51 • Number of events 10 • Adverse events were followed for 30 days after cessation of treatment	15.7% 8/51 • Number of events 9 • Adverse events were followed for 30 days after cessation of treatment
General disorders Fatigue (Asthenia, Lethargy, Malaise)	61.4% 27/44 • Number of events 46 • Adverse events were followed for 30 days after cessation of treatment	45.1% 23/51 • Number of events 32 • Adverse events were followed for 30 days after cessation of treatment	52.9% 27/51 • Number of events 49 • Adverse events were followed for 30 days after cessation of treatment
General disorders Fever (In The Absence Of Neutropenia, Where Neutropenia Is Defined As	11.4% 5/44 • Number of events 7 • Adverse events were followed for 30 days after cessation of treatment	3.9% 2/51 • Number of events 2 • Adverse events were followed for 30 days after cessation of treatment	3.9% 2/51 • Number of events 2 • Adverse events were followed for 30 days after cessation of treatment
Metabolism and nutrition disorders Glucose, Serum-High (Hyperglycemia)	13.6% 6/44 • Number of events 7 • Adverse events were followed for 30 days after cessation of treatment	5.9% 3/51 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment	11.8% 6/51 • Number of events 13 • Adverse events were followed for 30 days after cessation of treatment
Ear and labyrinth disorders Hearing (without monitoring program)	4.5% 2/44 • Number of events 2 • Adverse events were followed for 30 days after cessation of treatment	0.00% 0/51 • Adverse events were followed for 30 days after cessation of treatment	3.9% 2/51 • Number of events 2 • Adverse events were followed for 30 days after cessation of treatment
Gastrointestinal disorders Heartburn/Dyspepsia	4.5% 2/44 • Number of events 2 • Adverse events were followed for 30 days after cessation of treatment	7.8% 4/51 • Number of events 4 • Adverse events were followed for 30 days after cessation of treatment	2.0% 1/51 • Number of events 1 • Adverse events were followed for 30 days after cessation of treatment
Investigations Hemoglobin	38.6% 17/44 • Number of events 24 • Adverse events were followed for 30 days after cessation of treatment	25.5% 13/51 • Number of events 21 • Adverse events were followed for 30 days after cessation of treatment	47.1% 24/51 • Number of events 43 • Adverse events were followed for 30 days after cessation of treatment
Gastrointestinal disorders Hemorrhage, Gi - Rectum	0.00% 0/44 • Adverse events were followed for 30 days after cessation of treatment	5.9% 3/51 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment	5.9% 3/51 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment
Respiratory, thoracic and mediastinal disorders Hemorrhage, Pulmonary/Upper Respiratory - Bronchopulmonary Nos	9.1% 4/44 • Number of events 5 • Adverse events were followed for 30 days after cessation of treatment	2.0% 1/51 • Number of events 1 • Adverse events were followed for 30 days after cessation of treatment	0.00% 0/51 • Adverse events were followed for 30 days after cessation of treatment
Respiratory, thoracic and mediastinal disorders Hemorrhage, Pulmonary/Upper Respiratory - Nose	4.5% 2/44 • Number of events 2 • Adverse events were followed for 30 days after cessation of treatment	5.9% 3/51 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment	2.0% 1/51 • Number of events 1 • Adverse events were followed for 30 days after cessation of treatment
Vascular disorders Hypotension	6.8% 3/44 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment	7.8% 4/51 • Number of events 5 • Adverse events were followed for 30 days after cessation of treatment	3.9% 2/51 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment
Respiratory, thoracic and mediastinal disorders Hypoxia	4.5% 2/44 • Number of events 2 • Adverse events were followed for 30 days after cessation of treatment	2.0% 1/51 • Number of events 1 • Adverse events were followed for 30 days after cessation of treatment	3.9% 2/51 • Number of events 2 • Adverse events were followed for 30 days after cessation of treatment
Infections and infestations Infection With Normal Anc Or Grade 1 Or 2 Neutrophils - Bronchus	4.5% 2/44 • Number of events 2 • Adverse events were followed for 30 days after cessation of treatment	2.0% 1/51 • Number of events 1 • Adverse events were followed for 30 days after cessation of treatment	2.0% 1/51 • Number of events 1 • Adverse events were followed for 30 days after cessation of treatment
Immune system disorders Injection Site Reaction/Extravasation Changes	4.5% 2/44 • Number of events 4 • Adverse events were followed for 30 days after cessation of treatment	0.00% 0/51 • Adverse events were followed for 30 days after cessation of treatment	2.0% 1/51 • Number of events 7 • Adverse events were followed for 30 days after cessation of treatment
Psychiatric disorders Insomnia	6.8% 3/44 • Number of events 4 • Adverse events were followed for 30 days after cessation of treatment	11.8% 6/51 • Number of events 6 • Adverse events were followed for 30 days after cessation of treatment	11.8% 6/51 • Number of events 6 • Adverse events were followed for 30 days after cessation of treatment
Investigations Leukocytes (Total Wbc)	13.6% 6/44 • Number of events 17 • Adverse events were followed for 30 days after cessation of treatment	0.00% 0/51 • Adverse events were followed for 30 days after cessation of treatment	5.9% 3/51 • Number of events 4 • Adverse events were followed for 30 days after cessation of treatment
Psychiatric disorders Mood Alteration - Anxiety	9.1% 4/44 • Number of events 4 • Adverse events were followed for 30 days after cessation of treatment	5.9% 3/51 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment	5.9% 3/51 • Number of events 5 • Adverse events were followed for 30 days after cessation of treatment
Psychiatric disorders Mood Alteration - Depression	2.3% 1/44 • Number of events 1 • Adverse events were followed for 30 days after cessation of treatment	5.9% 3/51 • Number of events 6 • Adverse events were followed for 30 days after cessation of treatment	3.9% 2/51 • Number of events 2 • Adverse events were followed for 30 days after cessation of treatment
Gastrointestinal disorders Mucositis/Stomatitis (Clinical Exam) - Oral Cavity	2.3% 1/44 • Number of events 4 • Adverse events were followed for 30 days after cessation of treatment	9.8% 5/51 • Number of events 7 • Adverse events were followed for 30 days after cessation of treatment	13.7% 7/51 • Number of events 8 • Adverse events were followed for 30 days after cessation of treatment
Gastrointestinal disorders Mucositis/Stomatitis (Functional/Symptomatic) - Oral Cavity	6.8% 3/44 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment	2.0% 1/51 • Number of events 1 • Adverse events were followed for 30 days after cessation of treatment	2.0% 1/51 • Number of events 1 • Adverse events were followed for 30 days after cessation of treatment
Musculoskeletal and connective tissue disorders Muscle Weakness, Generalized Or Specific Area (Not Due To Neuropathy)	15.9% 7/44 • Number of events 7 • Adverse events were followed for 30 days after cessation of treatment	3.9% 2/51 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment	7.8% 4/51 • Number of events 5 • Adverse events were followed for 30 days after cessation of treatment
Gastrointestinal disorders Nausea	20.5% 9/44 • Number of events 32 • Adverse events were followed for 30 days after cessation of treatment	17.6% 9/51 • Number of events 11 • Adverse events were followed for 30 days after cessation of treatment	31.4% 16/51 • Number of events 30 • Adverse events were followed for 30 days after cessation of treatment
Nervous system disorders Neuropathy: Sensory	9.1% 4/44 • Number of events 5 • Adverse events were followed for 30 days after cessation of treatment	0.00% 0/51 • Adverse events were followed for 30 days after cessation of treatment	3.9% 2/51 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment
Investigations Neutrophils/Granulocytes (Anc/Agc)	18.2% 8/44 • Number of events 16 • Adverse events were followed for 30 days after cessation of treatment	0.00% 0/51 • Adverse events were followed for 30 days after cessation of treatment	5.9% 3/51 • Number of events 3 • Adverse events were followed for 30 days after cessation of treatment
Eye disorders Ocular/Visual - Other (Specify, __)	4.5% 2/44 • Number of events 2 • Adverse events were followed for 30 days after cessation of treatment	0.00% 0/51 • Adverse events were followed for 30 days after cessation of treatment	0.00% 0/51 • Adverse events were followed for 30 days after cessation of treatment