Fluorouracil With or Without Cisplatin in Treating Patients With Advanced or Metastatic Cancer of the Pancreas

Infusional 5-Fluorouracil With or Without Cisplatin and With or Without Chronomodulation Against Locally-Advanced or Metastatic Pancreatic Cancer. A Multicenter Randomized Phase III Trial.

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving drugs in different ways may kill more tumor cells. It is not yet known whether fluorouracil plus cisplatin are more effective than fluorouracil alone in treating patients with metastatic cancer of the pancreas.

PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil with or without cisplatin in treating patients who have advanced or metastatic cancer of the pancreas.

OBJECTIVES:

• Confirm the value of chronomodulated infusion with respect to survival in patients with locally advanced or metastatic pancreatic cancer.
• Test the value of adding cisplatin to fluorouracil in extending survival in these patients.

OUTLINE: This is a multicenter, randomized study.

The study design is a 2 X 2 factorial such that patients are allocated to one of 4 treatment groups involving the use or absence of chronomodulation and cisplatin (CDDP). Treatment in each of the 4 groups is repeated for 3 courses where each course is a 5-day course of treatment.

Patients in the first group receive a chronomodulated schedule based on delivery of fluorouracil (FU). Patients in the second group receive a chronomodulated schedule of FU and CDDP. Patients in the third and fourth experimental groups receive flat schedules of FU alone or FU and CDDP, respectively. Dosages of FU are increased across the three courses whereas dosages of CDDP remain constant.

Treatment is continued until disease progression, severe toxicity, or complete remission for more than 4 months occurs.

PROJECTED ACCRUAL: 200 patients will be accrued.

DISEASE CHARACTERISTICS:

• Histologic or cytologic proof of adenocarcinoma of the exocrine pancreas or of a metastasis associated with a radiologically identified pancreatic tumor
• Locally advanced and/or metastatic pancreatic cancer
• No measurable or evaluable target lesion is required
• No brain metastasis

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 40%-100%

Hematopoietic:

• WBC at least 3,000/mm^3
• Neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 3 times normal

Renal:

• Creatinine no greater than 1.24 mg/dL OR
• Creatinine clearance at least 80 mL/min

Cardiovascular:

• No overt cardiac disease

Other:

• No peripheral neuropathy
• No uncontrolled infectious or chronic disease
• No second primary except in situ carcinoma of the cervix, or basal or squamous cell carcinoma of the skin

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent immunologic therapy

Chemotherapy:

• No prior chemotherapy allowed

Endocrine therapy:

• No concurrent hormonal therapy
• At least 2 weeks since corticoid treatment

Radiotherapy:

• No prior radiotherapy allowed except as an analgesic treatment on metastasis

Surgery:

• Not specified