Gemcitabine With or Without Radiation Therapy in Treating Patients With Pancreatic Cancer

OBJECTIVES:

• Compare the overall survival and progression-free of patients with locally advanced, unresectable pancreatic cancer treated with gemcitabine with or without radiotherapy.
• Compare the objective response rate in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the quality of life (QOL) of patients treated with these regimens.
• Determine the effect of gemcitabine and radiotherapy on the QOL of patients with improved objective response rate and progression-free and overall survival.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to performance status (0 vs. 1) and weight loss within the past 6 months (less than 10% vs. 10% or more). Patients are randomized to 1 of 2 treatment arms.

Arm I (Gemcitabine alone):

• Induction: Patients receive gemcitabine intravenously (IV) over 30-60 minutes once weekly for 6 weeks followed by 1 week of rest.
• Consolidation: After the 1 week of rest, patients receive gemcitabine IV once weekly for 3 weeks. Treatment repeats every 4 weeks for 5 courses in the absence of disease progression or unacceptable toxicity.

Arm II (Gemcitabine with radiotherapy):

• Induction: Patients receive gemcitabine IV over 30-60 minutes once weekly for 6 weeks beginning on day 1. Patients also undergo concurrent radiotherapy 5 days a week for 5.5 weeks beginning on day 1.
• Consolidation: Approximately 4 weeks after completion of radiotherapy, patients receive gemcitabine IV over 30-60 minutes once weekly for 3 weeks. Treatment repeats every 4 weeks for 5 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, week 6, week 15 (for arm II), week 16 (for arm I), and 9 months.

Patients are followed every 3 months for 2 years and then every 6 months for 1 year. Patients who receive treatment beyond 3 years are followed for survival.

ACCRUAL: 74 patients were accrued for this study.

Inclusion criteria

• Histologically or cytologically confirmed adenocarcinoma of the pancreas

• Locally advanced or regional (encompassable within the same radiotherapy portals)
• Adenosquamous cancers are allowed
• Unresectable disease
• Measurable and/or non-measurable disease as determined by computed tomography (CT) scan or magnetic resonance imaging (MRI), which must be performed within 4 weeks prior to randomization.
• Age>=18
• ECOG Performance status of 0-1
• Life expectancy >= 12 weeks
• Adequate bone marrow reserve,liver and renal function within 2 weeks of randomization:

• Absolute granulocyte count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin less than 3 mg/dL (unless secondary to biliary obstruction or cholangitis)
• Serum glutamic-oxaloacetic (AST) less than 5 times upper limit of normal (ULN)
• Albumin greater than 2.5 g/dL
• Creatinine no greater than 1.5 times ULN
• Fertile patients must use effective contraception
• Willing and able to attend follow-up visits
• Concurrent enrollment on protocol ECOG-E1Y03 allowed
• More than 4 weeks since prior investigational agents

Exclusion criteria

• Candidate for surgical excision based on local extent of disease (e.g., T3, N1, M0)
• Stage M1 disease
• Small cell, mucinous cystadenocarcinoma, islet cell or papillary cystic histology
• Pregnant or nursing
• Active infection within within 4 weeks of randomization
• Malignancy within the past 5 years except nonmelanoma skin cancer, carcinoma in situ of the cervix, or organ-confined prostate cancer (Gleason score no greater than 7)
• History of active collagen vascular disease (i.e., systemic lupus erythematosus, rheumatoid arthritis, or scleroderma)
• Signs or symptoms of peptic or duodenal ulcer disease
• Concurrent serious systemic disorders that are incompatible with study participation
• Prior chemotherapy for pancreatic cancer
• Prior radiotherapy
• Concurrent intensity modulated radiotherapy