RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in
chemotherapy use different ways to stop tumor cells from dividing so they stop growing or
die. Combining radiation therapy with chemotherapy may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of gemcitabine plus radiation therapy in
treating patients with pancreatic cancer that can not be surgically removed.
OBJECTIVES: I. Determine the maximum tolerated dose of gemcitabine in combination with
radiation therapy to patients with locally advanced and/or unresectable adenocarcinoma of
the pancreas. II. Determine the dose limiting toxic effects of this combination therapy in
these patients. III. Evaluate the ability of these patients to tolerate induction and then
maintenance therapy with gemcitabine preceding and following combination therapy. IV.
Evaluate the efficacy (response rate, pattern of failure, and survival) of this combination
therapy in these patients.
OUTLINE: This is a dose escalation study of gemcitabine. Part I: Patients receive
gemcitabine as a continuous infusion over 30 minutes once weekly for 3 weeks followed by 1
week of rest. Part II: Gemcitabine IV is administered as a 30 minute infusion twice a week
(Monday and Thursday) for 5-6 weeks. Patients receive radiation therapy 5 days a week for
5-6 weeks. In the absence of dose-limiting toxicity (DLT) in the first 6 patients treated,
subsequent cohorts of 6 patients each receive escalating doses of gemcitabine on the same
schedule. If DLT occurs in 2 of 6 patients at a given dose level, then dose escalation
ceases and the next lower dose is declared the maximum tolerated dose. Part III: In the
absence of toxicity and disease progression, patients continue gemcitabine for 3 additional
courses. Maintenance gemcitabine starts 4 weeks after the completion of radiation therapy
and is administered once weekly for 3 weeks followed by 1 week of rest. Patients are
followed until death.
PROJECTED ACCRUAL: This study will accrue 15-30 patients in approximately 24 months.
DISEASE CHARACTERISTICS: Histologically or cytologically proven locally advanced and/or
unresectable adenocarcinoma of the pancreas No metastatic disease No completely resected
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% OR ECOG
0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3000/mm3 Platelet count at
least 100,000/mm3 Hepatic: Bilirubin less than 2.0 mg/dL Renal: Creatinine no greater than
1.5 mg/dL Cardiovascular: No congestive heart failure No New York Heart Association class
III and IV heart disease Other: Not pregnant No concurrent medical problems that would
increase the side effects or morbidity of chemoradiation No concurrent medical condition
that would make patient ineligible to receive external beam radiation such as: Crohn's
disease Inflammatory bowel disease No active infection requiring systemic antibiotics
PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior
gemcitabine No prior chemotherapy for pancreatic cancer Endocrine therapy: Not specified
Radiotherapy: No prior radiotherapy to the pancreas Surgery: Not specified