Phase II clinical trial with 5-fluorouracil, recombinant interferon-α-2b, and cisplatin for patients with metastatic or regionally advanced carcinoma of the esophagus

BACKGROUND. Recombinant interferon-α (IFN) augments the cytotoxicity of both 5-fluorouracil (5-FU) and cisplatin in vitro. A Phase II study of 5-FU and IFN resulted in response rates of 25-27% in patients with metastatic esophageal carcinoma. METHODS. A Phase II trial was initiated to determine the clinical utility of a three-drug combination (FIP) in patients with regionally advanced or metastatic esophageal carcinoma. Eligibility included biopsy-proven Stage III or IV squamous cell carcinoma or adenocarcinoma of the esophagus with no prior chemotherapy, adequate performance status, nutritional status, bone marrow, hepatic and renal function, and signed informed consent. Patients were treated in the exact sequence of IFN ⇒ cisplatin ⇒ 5-FU. Patients received 5-FU, 750 mg/m²/day for 5 days followed by weekly bolus therapy at the same dose; cisplatin, 100 mg/m² on Day 1, followed by weekly therapy, 25 mg/m² 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 μg/kg subcutaneously 5 times/week. No patients received radiotherapy. RESULTS. Twenty-four patients were enrolled; 23 were eligible, and 1 was excluded on pathology review (patient was found to have a leiomyoblastoma). The demographics of the population were: median age, 63 years (range, 43-73 years); 18 male patients; squamous cell carcinoma: adenocarcinoma ratio, 22:1; and Stage III:IV ratio, 10:13. Grade 3-4 National Cancer Institute Common Toxicity Criteria toxicities included: leukopenia (13), thrombocytopenia (14), and infection (9). Grade 3 diarrhea, mucositis, and vomiting occurred in 6 patients, 4 patients, and 1 patient, respectively. There were two instances of sudden death, likely related to tumor progression. Major responses occurred in 15 of 23 patients (65%; 95% confidence interval, 43%, 85%) (1 complete response, 14 partial responses). The median survival was 8.6 months; with a median follow-up of 26 months, estimated 30-month survival was 31%. CONCLUSIONS. This regimen, although moderately toxic, has substantial activity in metastatic and regionally advanced squamous cell carcinoma of the esophagus. Further investigations should be conducted to determine the role of IFN in the treatment of esophageal carcinoma.