Combination Chemotherapy as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors of the Duodenum or Pancreas That Cannot Be Removed By Surgery

OBJECTIVES:

Primary

• Determine the 6-month progression-free survival rate in patients with unresectable locally advanced or metastatic neuroendocrine tumors of the duodenum/pancreas treated with fluorouracil, leucovorin calcium, and irinotecan hydrochloride as first-line chemotherapy.

Secondary

• Determine tumor and biologic response at 6, 12, 18, and 24 months in patients treated with this regimen.
• Determine the duration of response of the primary tumor in patients treated with this regimen.
• Determine the tolerability of this regimen in these patients.
• Determine the progression-free survival of patients treated with this regimen.
• Determine the overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive irinotecan hydrochloride IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months for 1 year and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of neuroendocrine tumor of the duodenum/pancreas by histology or bone scan
• Functional or nonfunctional tumor

• Tumor meets ≥ 1 of the following criteria:

• Hepatic or extrahepatic metastases
• Progressive locally advanced tumor (primary or adenopathies)
• Unresectable disease
• Tumor differentiated and meets the following criteria:

• Ki 67 ≤ 15%
• Less than 10 mitoses per 10 large fields
• Measurable or evaluable disease

• Target lesions must meet 1 of the following criteria within the past 6 months:

• Increase of 20% in the longest diameter
• New metastases detected
• Minimum size of lesions must be 1 of the following:

• More than 15 mm for metastases
• More than 50 mm for primary tumor or local lymph nodes

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Creatinine ≤ 1.5 mg/dL
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 1.8 mg/dL
• No coronary insufficiency or symptomatic cardiac disease
• No intestinal obstruction, enteropathy, or uncontrolled chronic diarrhea
• No Gilbert's disease
• No psychological, social, familial, or geographic condition that would preclude study treatment
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 6 months after completion of study therapy
• No other condition that would preclude study therapy

PRIOR CONCURRENT THERAPY:

• No prior adjuvant radiotherapy
• At least 3 months since prior interferon
• Prior somatostatin analogs or antisecretories allowed
• No other prior treatment for this cancer
• No concurrent radiotherapy to the target lesion