Combination Chemotherapy Plus Interferon Alfa Followed by Filgrastim in Treating Patients With Gastrointestinal Tract Cancer

OBJECTIVES: I. Determine the objective response rates in patients with unresectable locally
advanced or advanced gastrointestinal malignancy treated with intravenous hydroxyurea,
fluorouracil, interferon alfa, and filgrastim (G-CSF). II. Determine the toxic effects of
this regimen in these patients. III. Determine the reversal of toxic effects of this regimen
in these patients.

OUTLINE: Patients are stratified according to site of primary disease (hepatobiliary vs
gastric vs pancreatic). Patients receive fluorouracil IV over 48 hours and hydroxyurea IV
over 48 hours on days 1, 8, 22, and 29. Patients also receive interferon alfa subcutaneously
(SC) on days 1, 3, and 5 and filgrastim (G-CSF) SC on days 3-6 of weeks 1, 2, 4, and 5.
Treatment repeats every 6 weeks in the absence of disease progression or unacceptable
toxicity.

PROJECTED ACCRUAL: A total of 31-60 patients (18-33 with hepatobiliary or gastric cancer and
13-27 with pancreatic cancer) will be accrued for this study.

DISEASE CHARACTERISTICS: Histologically confirmed pancreatic, gastric, biliary system, or
hepatocellular carcinoma beyond the scope of surgical resection Gastrointestinal tract
carcinoid tumor or carcinoma of the small bowel allowed Bidimensionally measurable disease
Ineligible for ECOG 6296 (gastric cancer) No brain metastases, unless completely resected
and CT scan of the brain is normal

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: Not
specified Hematopoietic: WBC at least 4,000/mm3 Platelet count at least 100,000/mm3
Hepatic: Bilirubin less than 3 times normal SGOT less than 3 times normal Renal: Creatinine
no greater than 2.0 mg/dL Cardiovascular: No New York Heart Association class III or IV
heart disease No chronic or uncontrolled angina No significant coronary artery disease
(even if asymptomatic) on cardiac catheterization or thallium stress test, in patients with
a history of atherosclerotic heart disease No congestive heart failure No arrhythmia
Pulmonary: No chronic obstructive pulmonary disease No chronic pulmonary disease, including
asthma, chronic bronchitis, emphysema, sarcoid, or bronchiectasis Neurologic: No cerebellar
disease No seizure disorder Other: HIV negative No active or serious underlying infection
No AIDS No psychiatric illness No organic mental syndrome No major psychoaffective disorder
No poorly controlled diabetes mellitus No serious underlying illness that would preclude
study No recent history of alcohol or drug abuse Not pregnant or nursing Negative pregnancy
test Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy Chemotherapy: No
prior systemic chemotherapy for advanced disease Prior fluorouracil or gemcitabine as
radiosensitizer allowed No other prior chemotherapy Endocrine therapy: No concurrent
systemic steroids No concurrent hormonal therapy (excluding birth control pills) No
concurrent steroids as antiemetics or for chronic treatment Radiotherapy: At least 1 month
since prior radiotherapy Surgery: See Disease Characteristics Recovered from prior surgery
Other: At least 1 week since prior beta blockers No concurrent chronic treatment with
aspirin, non-steroidal anti-inflammatory drugs, antihistamines, antianginal medication,
extraordinary antihypertensive regimens, or antiarrhythmics (except cardiac glycosides)