• Toxicity as measured by NCI CTC v2.0 [ Designated as safety issue: Yes ]
• Quality of life as measured by EORTC QLQ C-30 and ESPAC-QLQ at 3, 6, and 12 months, and then annually for 5 years [ Designated as safety issue: No ]
• Survival rate at 2 and 5 years [ Designated as safety issue: No ]

• Toxicity as measured by NCI CTC v2.0
• Quality of life as measured by EORTC QLQ C-30 and ESPAC-QLQ at 3, 6, and 12 months, and then annually for 5 years
• Survival rate at 5 years

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which chemotherapy regimen is more effective, or whether chemotherapy is more effective than observation, in treating pancreatic cancer after surgery.

PURPOSE: Phase III trial to compare the effectiveness of two chemotherapy regimens with no further therapy in treating patients who have completely resected pancreatic cancer.

OBJECTIVES:

Primary

• Compare the efficacy of adjuvant gemcitabine vs fluorouracil and leucovorin calcium (vs observation only in patients with ampullary or other pancreatic malignancy), in terms of overall survival, in patients with completely resected pancreatic cancer.

Secondary

• Compare the toxicity of these regimens in these patients.
• Compare the quality of life and 5-year survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to histology (ductal adenocarcinoma vs ampullary or other pancreatic malignancy), resection margin status, and participating country. Patients are randomized to 1 of 2 treatment arms. Randomization for patients with ampullary or other pancreatic malignancy includes an observation arm.

• Arm I: Patients receive leucovorin calcium IV and fluorouracil IV on days 1-5.
• Arm II: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15.
• Arm III (patients with ampullary or other pancreatic malignancy only): Patients undergo observation.

Treatment in arms I and II repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, 3, 6, and 12 months, and then annually for 5 years.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 1,030 patients with pancreatic adenocarcinoma (515 per arms I and II) will be accrued for this study.

• Drug: fluorouracil
• Drug: gemcitabine hydrochloride
• Drug: leucovorin calcium
• Procedure: observation

• Active Comparator: Patients receive leucovorin calcium IV and fluorouracil IV on days 1-5.
• Experimental: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15.
• No Intervention: Patients undergo observation.

DISEASE CHARACTERISTICS:

• Histologically confirmed ductal adenocarcinoma of the pancreas OR

• Histologically confirmed diagnosis of 1 of the following types of cancer:

  • Acinar cell carcinoma or cystadenocarcinoma of the pancreas
  • Cancers of the periampullary region
  • Cancers of the intrapancreatic part of the bile duct
  • Periampullary cancers of uncertain origin

• Complete macroscopic resection (R0 or R1 resection)

  • Histological examination of all resection margins required
• No stage IVB disease
• No evidence of malignant ascites
• No liver or peritoneal metastases
• No evidence of spread to other distant abdominal or extra-abdominal organs
• No pancreatic lymphoma

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• More than 3 months

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant
• Able to participate in long-term follow-up
• No other prior or concurrent malignancy except curatively treated basal cell skin cancer or carcinoma in situ of the cervix
• No serious medical or psychological condition that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No neoadjuvant chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics
• Recovered from prior resection

• NCIC Clinical Trials Group
• Australasian Gastro-Intestinal Trials Group