Gemcitabine With or Without Combination Chemotherapy and Radiation Therapy in Treating Patients With Nonmetastatic Pancreatic Cancer That Cannot Be Removed By Surgery

OBJECTIVES:

Primary

• Compare the overall survival of patients with nonresectable, nonmetastatic adenocarcinoma of the pancreas treated with gemcitabine hydrochloride with vs without fluorouracil, cisplatin, and radiotherapy followed by gemcitabine hydrochloride.

Secondary

• Compare the toxicities of these regimens in these patients.
• Compare the objective response (complete, partial, or stable) in patients treated with these regimens.
• Compare the clinical benefit, in terms of general condition and weight maintenance in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to WHO performance status (0 or 1 vs 2), initial treatment (laparotomy with or without bilio-digestive diversion) (yes vs no), and peritoneal cytology (positive vs negative). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cisplatin IV over 15 minutes on days 1-5 and 29-33 and fluorouracil IV continuously on days 1-40. Patients also undergo radiotherapy daily, 5 days a week, for 6 weeks.
• Arm II: Patients receive gemcitabine hydrochloride IV over 15 minutes on day 1. Treatment repeats every 7 days for 7 weeks.

Beginning in week 11 of arm I or week 9 of arm II, patients receive gemcitabine hydrochloride IV over 15 minutes on days 1, 8, and 15. Treatment repeats every 4 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 190 patients will be accrued for this trial.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas
• No neuroendocrine or other histologies
• No extra-abdominal metastases
• No hepatic or peritoneal metastases by celioscopy

• Peritoneal carcinomatous (cytology positive by peritoneal lavage) may be allowed
• Nonresectable disease meeting ≥ 1 of the following criteria:

• Arterial invasion
• Mesenteric-portal vein invasion > 15 mm and or less than hemicircumference
• Satellite adenopathies encompassed in the radiation field

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Bilirubin < 1.75 mg/dL
• Creatinine < 1.5 mg/dL
• WBC > 1,500/mm³
• Platelet count > 100,000/mm³
• No major organ disorder, including cardiac or coronary insufficiency
• Prothrombin time > 80%
• No psychiatric or social condition that would preclude study therapy
• No other malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No contraindications to radiotherapy or chemotherapy
• No intractable pancreatic pain not relieved by morphine and/or analgesic radiotherapy

PRIOR CONCURRENT THERAPY:

• No prior adjuvant or palliative chemotherapy or radiotherapy
• Prior surgical diversion of the biliary and/or digestive tract allowed