Chemotherapy in Treating Patients With Locally Advanced or Metastatic Cancer of the Pancreas or Bile Duct

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining gemcitabine, leucovorin, and fluorouracil in treating patients who have locally advanced or metastatic cancer of the pancreas or bile duct.

OBJECTIVES: I. Determine the response rate, in terms of WHO objectives and clinical benefit, in patients with locally advanced or metastatic pancreatic or biliary adenocarcinoma treated with gemcitabine, leucovorin calcium, and fluorouracil. II. Determine the tolerance of this regimen in this patient population. III. Determine the survival without disease progression in patients treated with this regimen. IV. Determine the overall survival in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients receive leucovorin calcium IV over 2 hours followed by fluorouracil IV over 24 hours on day 1 followed by gemcitabine IV over 80-150 minutes on day 2. Treatment repeats every 2 weeks for a minimum of 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete response may continue chemotherapy for up to 1 year. Patients with locally advanced disease after 3 months of chemotherapy may receive concurrent radiotherapy with chemotherapy for 5 weeks, or may undergo surgical resection. Fluorouracil-based chemotherapy (with or without radiotherapy) may then resume after surgery. Patients are followed for survival.

PROJECTED ACCRUAL: A total of 14-39 patients will be accrued for this study.

• Extrahepatic Bile Duct Cancer
• Pancreatic Cancer

• Drug: fluorouracil
• Drug: gemcitabine hydrochloride
• Drug: leucovorin calcium
• Procedure: conventional surgery
• Radiation: radiation therapy

• Andre T, Noirclerc M, Hammel P, Meckenstock R, Landi B, Cattan S, Selle F, Codoul JF, Guerrier-Parmentier B, Mokhtar R, Louvet C; GERCOR. Phase II study of leucovorin, 5-fluorouracil and gemcitabine for locally advanced and metastatic pancreatic cancer (FOLFUGEM 2). Gastroenterol Clin Biol. 2004 Aug-Sep;28(8-9):645-50. Review.
• Huguet F, Andre T, Hammel P, Artru P, Balosso J, Selle F, Deniaud-Alexandre E, Ruszniewski P, Touboul E, Labianca R, de Gramont A, Louvet C. Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies. J Clin Oncol. 2007 Jan 20;25(3):326-31.

DISEASE CHARACTERISTICS: Histologically confirmed pancreatic or biliary duct adenocarcinoma Metastatic or locally advanced No cerebral metastasis Surgically unresectable

PATIENT CHARACTERISTICS: Age: 18 to 75 Performance status: ECOG 0-2 Life expectancy: More than 12 months Hematopoietic: Absolute neutrophil count greater than 1,500/mm3 Platelet count greater than 100,000/mm3 Hepatic: Alkaline phosphatase less than 5 times normal Bilirubin less than 1.5 times normal Renal: Creatinine less than 1.5 times normal No uncontrolled or persistent hypercalcemia Cardiovascular: No severe cardiac failure Pulmonary: No severe respiratory failure Other: No other malignant tumor considered incurable or untreatable No uncontrolled pain No psychological, familial, social, or geographical reasons that would preclude study

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: No concurrent corticosteroids except as antiemetic Radiotherapy: No prior radiotherapy Surgery: See Disease Characteristics