Triacetyluridine and Fluorouracil Compared With Gemcitabine in Treating Patients With Unresectable Locally Advanced, or Metastatic Pancreatic Cancer

OBJECTIVES:

• Compare the survival of patients with unresectable locally advanced or metastatic pancreatic cancer treated with triacetyluridine and high-dose fluorouracil vs gemcitabine.
• Compare the time to tumor progression, overall response rate, and response duration in patients treated with these regimens.
• Compare the safety of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to disease stage (II or III vs IV). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive high-dose fluorouracil (5-FU) IV over 30 minutes once weekly on weeks 1-3 followed by 1 week of rest. After each dose of 5-FU, patients receive oral triacetyluridine every 8 hours for a total of 8 doses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive gemcitabine IV over 30 minutes once weekly on weeks 1-7 followed by 1 week of rest (course 1). Subsequent courses are given on weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 260 patients (130 per treatment arm) will be accrued for this study within 30 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas

• Unresectable locally advanced or metastatic disease

• Stage II, III, or IV
• Measurable or evaluable disease
• No elevated tumor marker (CA 19-9) only
• No clinically significant third-space fluid accumulation (e.g., ascites or pleural effusion)
• No carcinoid, islet cell, or lymphoma of the pancreas
• No prior or concurrent brain or leptomeningeal metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• WBC at least 3,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.5 g/dL

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• ALT or AST less than 3 times upper limit of normal (ULN) (5 times ULN if liver metastases present)
• No uncontrolled hepatic dysfunction

Renal:

• Creatinine less than 2.0 mg/dL
• No uncontrolled renal dysfunction

Cardiovascular:

• No uncontrolled cardiovascular disease requiring therapy, including the following:

• Angina
• Arrhythmias
• Uncompensated cardiac failure
• Myocardial infarction within the past 6 months

Pulmonary:

• No uncontrolled pulmonary dysfunction

Gastrointestinal:

• Able to take and/or retain oral medication
• No uncontrolled malabsorption syndrome or any other condition that would interfere with intestinal absorption

Other:

• No known allergy to fluorouracil (5-FU), gemcitabine, triacetyluridine, or any of their components
• No dihydropyrimidine-dehydrogenase deficiency
• No active uncontrolled infection
• No uncontrolled neurologic or psychiatric dysfunction
• No other malignancy except previously resected basal cell cancer or curatively resected stage I or less cervical cancer that has been disease free for at least 5 years
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent biologic therapy (including immunotherapy) for cancer

Chemotherapy:

• No prior chemotherapy for cancer other than as a radiosensitizer
• No prior 5-FU or gemcitabine other than as a radiosensitizer
• No prior triacetyluridine
• No other concurrent chemotherapy (including leucovorin calcium) for cancer

Endocrine therapy:

• No concurrent hormonal therapy for cancer
• Concurrent megestrol, oral contraceptives, or postmenopausal estrogen replacement therapy allowed

Radiotherapy:

• Prior radiotherapy allowed
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• Prior resection of pancreas allowed

Other:

• At least 30 days since prior investigational drug or therapeutic device
• No other concurrent anticancer therapy
• No other concurrent investigational drugs or devices
• No concurrent drugs that would interact adversely with 5-FU or gemcitabine