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

Gemcitabine Plus Capecitabine Versus Gemcitabine Alone In Advanced Pancreatic Cancer. A Randomized Phase III Trial

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if gemcitabine is more effective with or without capecitabine in treating pancreatic cancer.

PURPOSE: Randomized phase III trial to determine the effectiveness of gemcitabine with or without capecitabine in treating patients who have 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