Gemcitabine With or Without Capecitabine in Treating Patients With Advanced Pancreatic Cancer

OBJECTIVES:

• Compare the overall survival of patients with advanced pancreatic cancer treated with gemcitabine with or without capecitabine.
• Compare the clinical benefit response, objective tumor response, duration of response, and time to progression in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to metastases (yes vs no), pain (yes vs no), Karnofsky performance status (60-80% vs 90-100%), and participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients initially receive gemcitabine IV over 30 minutes weekly for 7 weeks. After 1 week of rest, patients receive gemcitabine IV over 30 minutes weekly for 3 weeks. Treatment then repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, weekly for weeks 2-7, and then before each gemcitabine administration.

Patients are followed every 9 weeks.

PROJECTED ACCRUAL: A total of 300 patients (150 per treatment arm) will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed primary inoperable or metastatic pancreatic adenocarcinoma
• No CNS metastases

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10.0 g/dL

Hepatic:

• Bilirubin no greater than 5 times normal
• AST/ALT no greater than 5 times normal
• Alkaline phosphatase no greater than 5 times normal

Renal:

• Creatinine clearance at least 30 mL/min

Gastrointestinal:

• No grade 2 or greater nausea or grade 1 or greater vomiting
• No medical condition that would interfere with taking oral medications or with gastrointestinal absorption (e.g., small bowel obstruction)

Other:

• No prior unanticipated severe reaction to fluoropyrimidine therapy
• No known hypersensitivity to fluorouracil
• No known dihydropyrimidine dehydrogenase deficiency
• No active infection
• No other serious concurrent systemic disorders that would preclude study participation
• No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or basal cell skin cancer
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior capecitabine
• No prior chemotherapy for advanced pancreatic cancer
• At least 1 year since prior radiochemotherapy for pancreatic cancer

Endocrine therapy:

• Not specified

Radiotherapy:

• See Chemotherapy
• At least 1 year since prior adjuvant radiotherapy for pancreatic cancer
• No concurrent radiotherapy

Surgery:

• Prior Whipple procedure or duodenal bypass allowed

Other:

• At least 1 month since prior investigational agents
• No concurrent sorivudine or its chemically related analogues (e.g., brivudine)
• No other concurrent anticancer or investigational drugs