Trial Outcomes & Findings for Multimodality Treatment for Women With Stage II, Stage III, or Stage IV Breast Cancer (NCT NCT00006110)

Last Updated: 2017-07-31

Results Overview

Doxorubicin + cyclophosphamide in combination with paclitaxel and trastuzumab (AC-TP) Associated Systolic Dysfunction. Systolic function was measured by the ventricular ejection fraction (LVEF). LVEF is a measurement in determining how well your heart is pumping out blood and in diagnosing and tracking heart failure.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

82 participants

Primary outcome timeframe

78 weeks (1.5 years)

Results posted on

2017-07-31

Participant Flow

Participants were recruited from University of North Carolina (UNC) at Chapel Hill and Wake Forest University School of Medicine.

85 patients consented to treatment. 3 patients were consented but not treated.

Participant milestones

Participant milestones
Measure	Experimental: Herceptin With or Without Radiation Patients will receive Adriamycin/Cytoxan (4AC) followed by Taxol plus weekly Herceptin either neo-adjuvantly or adjuvantly. Eligible patients will go on to radiation then all patients will receive additional Herceptin every three weeks for 40 weeks.	Experimental: Non-Herceptin With or Without Radiation Patients with high-risk human epidermal growth factor receptor 2 (HER-2) non-overexpressing tumors and those whose tumors overexpress the protein but who refuse or are ineligible for Herceptin® will be treated with conventional 4AC followed by Taxol® without Herceptin®. This will be followed by surgery then either radiation or no radiation.
Overall Study STARTED	52	30
Overall Study COMPLETED	52	30
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Multimodality Treatment for Women With Stage II, Stage III, or Stage IV Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental: Herceptin With or Without Radiation n=52 Participants Patients will receive Adriamycin/Cytoxan (4AC) followed by Taxol plus weekly Herceptin either neo-adjuvantly or adjuvantly. Eligible patients will go on to radiation then all patients will receive additional Herceptin every three weeks for 40 weeks.	Experimental: Non-Herceptin With or Without Radiation n=30 Participants Patients with high-risk human epidermal growth factor receptor 2 (HER-2) non-overexpressing tumors and those whose tumors overexpress the protein but who refuse or are ineligible for Herceptin® will be treated with conventional Adriamycin/Cytoxan (4AC) followed by Taxol® without Herceptin®. This will be followed by surgery then either radiation or no radiation.	Total n=82 Participants Total of all reporting groups
Age, Continuous	48 years n=5 Participants	48 years n=7 Participants	48 years n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	30 Participants n=7 Participants	82 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	16 Participants n=5 Participants	7 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) White	35 Participants n=5 Participants	21 Participants n=7 Participants	56 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	52 participants n=5 Participants	30 participants n=7 Participants	82 participants n=5 Participants
Type of Therapy Neoadjuvant	37 Participants n=5 Participants	30 Participants n=7 Participants	67 Participants n=5 Participants
Type of Therapy Adjuvant	15 Participants n=5 Participants	0 Participants n=7 Participants	15 Participants n=5 Participants
Estrogen Receptor Status +1	0 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants
Estrogen Receptor Status +2	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Estrogen Receptor Status +3	45 Participants n=5 Participants	3 Participants n=7 Participants	48 Participants n=5 Participants
Estrogen Receptor Status 0	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Estrogen Receptor Status fluorescence in-situ hybridization (FISH) Negative	0 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants
Estrogen Receptor Status FISH +	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Clinical Stage IIB	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Clinical Stage IIIA	20 Participants n=5 Participants	12 Participants n=7 Participants	32 Participants n=5 Participants
Clinical Stage IIIB	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Clinical Stage IIIC	8 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants
Clinical Stage IV	10 Participants n=5 Participants	3 Participants n=7 Participants	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: 78 weeks (1.5 years)

Population: LVEF data during AC-TP are complete on 50 patients. 2 are incomplete because of withdrawal (1) and progressive disease (1). 43 of the 52 patients underwent LVEF determination at 1.5 years.

Outcome measures

Outcome measures
Measure	Herceptin Regimen After AC n=52 Participants Patients in the adjuvant and neoadjuvant groups after receiving \[AC-TP\] Chemotherapy (doxorubicin \& cyclophosphamide).	Herceptin Regimen After TP n=50 Participants Patients in the adjuvant and neoadjuvant groups after receiving chemotherapy and Taxol + Herceptin.	Herceptin Regimen at 1.5 Years n=43 Participants Patients in the adjuvant and neoadjuvant groups.	Herceptin Regimen n=52 Participants Worst per-patient toxicity: represents the number of patients who had cardiac toxicity at any time during the study regardless of subsequent recovery of function.
Cardiac Toxicity of Weekly Taxol Given With Weekly Herceptin When Delivered Immediately Following Four Cycles of Standard Dose AC. Asymptomatic LVEF < 50%	1 Participants	8 Participants	3 Participants	11 Participants
Cardiac Toxicity of Weekly Taxol Given With Weekly Herceptin When Delivered Immediately Following Four Cycles of Standard Dose AC. Congestive Heart Failure	0 Participants	1 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 78 weeks (1.5 years)

Population: Protocol specifies that Response will be examined in patients who were treated neoadjuvantly. Because of this, only patients treated with Herceptin neoadjuvantly and non-Herceptin patients were included in this analysis. One patient was found unevaluable in the AC-P group and was not included in the analysis.

Measured by the Overall Response. 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	Herceptin Regimen After AC n=37 Participants Patients in the adjuvant and neoadjuvant groups after receiving \[AC-TP\] Chemotherapy (doxorubicin \& cyclophosphamide).	Herceptin Regimen After TP n=29 Participants Patients in the adjuvant and neoadjuvant groups after receiving chemotherapy and Taxol + Herceptin.	Herceptin Regimen at 1.5 Years Patients in the adjuvant and neoadjuvant groups.	Herceptin Regimen Worst per-patient toxicity: represents the number of patients who had cardiac toxicity at any time during the study regardless of subsequent recovery of function.
Overall Response	32 Participants	24 Participants	—	—

SECONDARY outcome

Timeframe: 5 years

Percent of patients receiving and not receiving Herceptin who are alive and disease-free at 5 years.

Outcome measures

Outcome measures
Measure	Herceptin Regimen After AC n=52 Participants Patients in the adjuvant and neoadjuvant groups after receiving \[AC-TP\] Chemotherapy (doxorubicin \& cyclophosphamide).	Herceptin Regimen After TP n=30 Participants Patients in the adjuvant and neoadjuvant groups after receiving chemotherapy and Taxol + Herceptin.	Herceptin Regimen at 1.5 Years Patients in the adjuvant and neoadjuvant groups.	Herceptin Regimen Worst per-patient toxicity: represents the number of patients who had cardiac toxicity at any time during the study regardless of subsequent recovery of function.
Disease-free Survival (DFS) in Patients Receiving and Not Receiving Herceptin®.	69 percentage of patients	60 percentage of patients	—	—

Adverse Events

Chemotherapy + Herceptin

Serious events: 7 serious events

Other events: 51 other events

Deaths: 15 deaths

Control: Non-Herceptin

Serious events: 1 serious events

Other events: 28 other events

Deaths: 13 deaths

Serious adverse events

Serious adverse events
Measure	Chemotherapy + Herceptin n=52 participants at risk Patients will receive Adriamycin/Cytoxan (4AC) followed by Taxol plus weekly Herceptin either neo-adjuvantly or adjuvantly. Eligible patients will go on to radiation then all patients will receive additional Herceptin every three weeks for 40 weeks.	Control: Non-Herceptin n=30 participants at risk Patients with high-risk HER-2 non-overexpressing tumors and those whose tumors overexpress the protein but who refuse or are ineligible for Herceptin® will be treated with conventional 4AC followed by Taxol® without Herceptin®. This will be followed by surgery then either radiation or no radiation.
Nervous system disorders Dizziness	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Nervous system disorders Seizure	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Respiratory, thoracic and mediastinal disorders Pleuritic pain	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Respiratory, thoracic and mediastinal disorders Dyspnea	3.8% 2/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Cardiac disorders Atrial Fibrillation	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Blood and lymphatic system disorders Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe	0.00% 0/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Infections and infestations Sepsis	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Nervous system disorders Nervous system disorders - Other, specify	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Nervous system disorders Peripheral neuropathy	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks

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

Restriction type: GT60

Measure	Chemotherapy + Herceptin n=52 participants at risk Patients will receive Adriamycin/Cytoxan (4AC) followed by Taxol plus weekly Herceptin either neo-adjuvantly or adjuvantly. Eligible patients will go on to radiation then all patients will receive additional Herceptin every three weeks for 40 weeks.	Control: Non-Herceptin n=30 participants at risk Patients with high-risk HER-2 non-overexpressing tumors and those whose tumors overexpress the protein but who refuse or are ineligible for Herceptin® will be treated with conventional 4AC followed by Taxol® without Herceptin®. This will be followed by surgery then either radiation or no radiation.
Gastrointestinal disorders Abdominal pain	5.8% 3/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Investigations Alanine aminotransferase increased	17.3% 9/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
Investigations Alkaline phosphatase	3.8% 2/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Immune system disorders Allergic reaction	13.5% 7/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Blood and lymphatic system disorders Anemia with transfusion	5.8% 3/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Blood and lymphatic system disorders Anemia without transfusion	42.3% 22/52 • Patients were followed every 3 weeks for 74 weeks	10.0% 3/30 • Patients were followed every 3 weeks for 74 weeks
Metabolism and nutrition disorders Anorexia	7.7% 4/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Psychiatric disorders Anxiety	3.8% 2/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Musculoskeletal and connective tissue disorders Arthralgia	17.3% 9/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
Investigations Aspartate aminotransferase increased	13.5% 7/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Cardiac disorders Atrial fibrillation	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
General disorders Chest pain	11.5% 6/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
General disorders Chills	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Gastrointestinal disorders Constipation	15.4% 8/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Renal and urinary disorders Cystitis	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Metabolism and nutrition disorders Dehydration	7.7% 4/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Nervous system disorders Depressed level of consciousness	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Psychiatric disorders Depression	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Gastrointestinal disorders Diarrhea	38.5% 20/52 • Patients were followed every 3 weeks for 74 weeks	6.7% 2/30 • Patients were followed every 3 weeks for 74 weeks
Nervous system disorders Dizziness	3.8% 2/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Nervous system disorders Dysgeusia	5.8% 3/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
Gastrointestinal disorders Dyspepsia	9.6% 5/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Respiratory, thoracic and mediastinal disorders Dyspnea	23.1% 12/52 • Patients were followed every 3 weeks for 74 weeks	6.7% 2/30 • Patients were followed every 3 weeks for 74 weeks
General disorders Edema	15.4% 8/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Respiratory, thoracic and mediastinal disorders Epistaxis	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Skin and subcutaneous tissue disorders Erythema multiforme	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Eye disorders Eye disorders - Other, specify	11.5% 6/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
General disorders Fatigue	50.0% 26/52 • Patients were followed every 3 weeks for 74 weeks	16.7% 5/30 • Patients were followed every 3 weeks for 74 weeks
Blood and lymphatic system disorders Febrile neutropenia	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
General disorders Fever	3.8% 2/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
General disorders General disorders and administration site conditions - Other, specify	3.8% 2/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Metabolism and nutrition disorders Glucose intolerance	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Skin and subcutaneous tissue disorders Hand-foot syndrome	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Nervous system disorders Headache	15.4% 8/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
Vascular disorders Hot flashes	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Metabolism and nutrition disorders Hyperglycemia	13.5% 7/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Skin and subcutaneous tissue disorders Hyperhidrosis	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Metabolism and nutrition disorders Hyperkalemia	7.7% 4/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
Metabolism and nutrition disorders Hypermagnesemia	7.7% 4/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Vascular disorders Hypertension	3.8% 2/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Metabolism and nutrition disorders Hypoalbuminemia	9.6% 5/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
Metabolism and nutrition disorders Hyponatremia	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Metabolism and nutrition disorders Hypophosphatemia	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Endocrine disorders Hypothyroidism	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Gastrointestinal disorders Ileus	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Infections and infestations Infection - Other (Specify, __)	0.00% 0/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
General disorders Infection w/o neutropenia	9.6% 5/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
Infections and infestations Infections and infestations - Other, specify	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Psychiatric disorders Insomnia	25.0% 13/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
Infections and infestations Kidney infection	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Vascular disorders Lymphedema	3.8% 2/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Psychiatric disorders Mood Alteration	3.8% 2/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Gastrointestinal disorders Mucositis	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Musculoskeletal and connective tissue disorders Myalgia	44.2% 23/52 • Patients were followed every 3 weeks for 74 weeks	66.7% 20/30 • Patients were followed every 3 weeks for 74 weeks
Skin and subcutaneous tissue disorders Nail loss	5.8% 3/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Gastrointestinal disorders Nausea	15.4% 8/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Nervous system disorders Neuropathy	75.0% 39/52 • Patients were followed every 3 weeks for 74 weeks	73.3% 22/30 • Patients were followed every 3 weeks for 74 weeks
Blood and lymphatic system disorders Neutropenia w/ fever	5.8% 3/52 • Patients were followed every 3 weeks for 74 weeks	6.7% 2/30 • Patients were followed every 3 weeks for 74 weeks
General disorders Neutropenia w/o fever	50.0% 26/52 • Patients were followed every 3 weeks for 74 weeks	56.7% 17/30 • Patients were followed every 3 weeks for 74 weeks
Skin and subcutaneous tissue disorders Rash	3.8% 2/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Cardiac disorders palpitations	3.8% 2/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Gastrointestinal disorders Pancreatitis	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Infections and infestations Pharyngitis	0.00% 0/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
Investigations Platelet count decreased	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
Gastrointestinal disorders Proctitis	5.8% 3/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Gastrointestinal disorders Rectal fistula	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Renal and urinary disorders Renal - Other (Specify)	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Infections and infestations Sepsis	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Cardiac disorders Sinus tachycardia	0.00% 0/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Skin and subcutaneous tissue disorders Skin hyperpigmentation	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Nervous system disorders Syncope	3.8% 2/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
Vascular disorders Thromboembolic event	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Nervous system disorders Transient ischemic attack	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Renal and urinary disorders Urinary frequency	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Gastrointestinal disorders Vomiting	0.00% 0/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks
Investigations Weight Gain	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	0.00% 0/30 • Patients were followed every 3 weeks for 74 weeks
Investigations Weight Loss	1.9% 1/52 • Patients were followed every 3 weeks for 74 weeks	3.3% 1/30 • Patients were followed every 3 weeks for 74 weeks