Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Pancreatic Cancer

OBJECTIVES:

Primary

• Compare the objective response rate in patients with metastatic adenocarcinoma of the pancreas treated with oxaliplatin, irinotecan, leucovorin calcium, and fluorouracil vs gemcitabine as first-line chemotherapy. (Phase II)
• Compare the survival of patients treated with these regimens. (Phase III)

Secondary

• Compare the toxicity of these regimens in these patients.
• Compare progression-free survival of patients treated with these regimens. (Phase III)
• Compare the overall response rate in patients treated with these regimens. (Phase III)
• Compare quality of life of patients treated with these regimens. (Phase III)

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oxaliplatin IV over 2 hours, irinotecan IV over 1½ hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5 minutes on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Courses repeat every 14 days.
• Arm II: Patients receive gemcitabine IV on days 1, 8, 15, 22, 29, 36, and 43. Beginning on day 57, patients receive gemcitabine IV once weekly for 3 weeks (days 57, 64, and 71). Courses repeat every 28 days.

PROJECTED ACCRUAL: A total of 348 patients (88 for phase II and 260 for phase III) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas

• No other pancreatic tumor type, including either of the following:

• Neuroendocrine tumor
• Acinar cell tumor
• Metastatic disease
• Measurable disease in an area not previously irradiated
• No cerebral metastases or meningeal involvement of the tumor

PATIENT CHARACTERISTICS:

Age

• 18 to 75

Performance status

• WHO 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (biliary drainage allowed)

Renal

• Creatinine < 120 mmol/L

Cardiovascular

• No prior myocardial infarction
• No prior angina
• No uncompensated cardiac or coronary insufficiency
• No symptomatic arrhythmia

Gastrointestinal

• No prior inflammatory bowel disease
• No prior chronic diarrhea
• No unresolved symptomatic occlusion or subocclusion of the bowel

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No ongoing active infection
• No other malignancy except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No contraindication to study treatment
• No other serious medical disorder that would preclude study treatment
• No psychiatric disorder or social or geographic situation that would preclude study participation
• Not detained or under the guardianship of another person

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified

Other

• No concurrent participation in another clinical trial using therapeutic experimental agents