Gemcitabine and Radiation Therapy Compared With Gemcitabine Alone in Treating Patients Who Have Undergone Surgery for Pancreatic Cancer

OBJECTIVES:

Phase II:

• Determine the feasibility of gemcitabine followed by chemoradiotherapy with gemcitabine vs gemcitabine alone after prior curative resection in patients with pancreatic head adenocarcinoma.
• Compare the tolerability of these regimens, in terms of acute and late toxicity, in these patients.

Phase III:

• Compare the disease-free and overall survival of patients treated with these regimens .
• Compare the quality of life of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Determine the sites of recurrence in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG/WHO performance status (0-1 vs 2), participating center, and N stage (N0 vs N1 vs NX). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Within 8 weeks after prior surgical resection, patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 4 weeks for 2 courses.

Patients then receive additional gemcitabine IV over 30 minutes on days 57, 64, 71, 78, 85, and 92. Beginning on day 57, patients also undergo radiotherapy once daily, 5 days a week, for 6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 4 weeks for 4 courses.

Quality of life (QOL) is assessed in both arms, according to the following schedules:

• Arm I: QOL is assessed at baseline; at 3 weeks after the beginning of chemoradiotherapy; after the completion of chemoradiotherapy; every 3 months for 2 years; and then every 6 months for 1 year.
• Arm II: QOL is assessed at baseline; at 12 weeks; at 16 weeks; every 3 months for 2 years; and then every 6 months for 1 year.

Patients are followed every 3 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 538 patients (269 per treatment arm) will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed pancreatic head adenocarcinoma
• Prior pancreaticoduodenectomy required

• Documented histological examination of surgical margins (R0), including retroperitoneal margin
• Performed within the past 8 weeks
• Any number of lymph nodes (less than 10 OR 10 or more) allowed
• No periampullary cancer

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC greater than 3,500/mm^3
• Platelet count greater than 150,000/mm^3
• Hemoglobin greater than 9.0 g/dL

Hepatic

• Bilirubin less than 1.5 times normal
• AST and ALT less than 3.0 times normal

Renal

• Creatinine less than 1.2 mg/dL

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix
• No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy

Chemotherapy

• No prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Other

• No other concurrent anticancer agents