PHASE-II CLINICAL-TRIAL WITH 5-FLUOROURACIL, RECOMBINANT INTERFERON-ALPHA-2B, AND CISPLATIN FOR PATIENTS WITH METASTATIC OR REGIONALLY ADVANCED-CARCINOMA OF THE ESOPHAGUS

BACKGROUND. Recombinant interferon-alpha (IFN) augments the cytotoxici ty of both 5-fluorouracil (5-FU) and cisplatin in vitro. A Phase II st udy of 5-FU and IFN resulted in response rates of 25-27% in patients w ith metastatic esophageal carcinoma. METHODS. A Phase II trial was ini tiated to determine the clinical utility of a three-drug combination ( FIP) in patients with regionally advanced or metastatic esophageal car cinoma. Eligibility included biopsy-proven Stage III or IV squamous ce ll carcinoma or adenocarcinoma of the esophagus with no prior chemothe rapy, adequate performance status, nutritional status, bone marrow, he patic and renal function, and signed informed consent. Patients were t reated in the exact sequence of IFN double right arrow cisplatin doubl e right arrow 5-FU. Patients received 5-FU, 750 mg/m(2)/day for 5 days followed by weekly bolus therapy at the same dose; cisplatin, 100 mg/ m(2) on Day 1, followed by weekly therapy, 25 mg/m(2) over the course of 1 hour; and IFN, 10 MU subcutaneously 3 times/week beginning on Day 1. All patients received sargramostim (granulocyte-macrophage colony- stimulating factor, Escherichia coli-derived), 5 mu g/kg subcutaneousl y 5 times/week. No patients received radiotherapy. RESULTS, Twenty-fou r patients were enrolled; 23 were eligible, and 1 was excluded on path ology review (patient was found to have a leiomyoblastoma). The demogr aphics of the population were: median age, 63 years (range, 43-73 year s); 18 male patients; squamous cell carcinoma: adenocarcinoma ratio, 2 2:1; and Stage III:IV ratio, 10:13. Grade 3-4 National Cancer Institut e Common Toxicity Criteria toxicities included: leukopenia (13), throm bocytopenia (14), and infection (9). Grade 3 diarrhea, mucositis, and vomiting occurred in 6 patients, 4 patients, and 1 patient, respective ly. There were two instances of sudden death, likely related to tumor progression. Major responses occurred in 15 of 23 patients (65%; 95% c onfidence interval, 43%, 85%) (1 complete response, 14 partial respons es). The median survival was 8.6 months; with a median follow-up of 26 months, estimated 30-month survival was 31%. CONCLUSIONS. This regime n, although moderately toxic, has substantial activity in metastatic a nd regionally advanced squamous cell carcinoma of the Esophagus. Furth er investigations should be conducted to determine the role of IFN in the treatment of esophageal carcinoma. (C) 1996 American Cancer Societ y.