PHASE-III TRIAL OF MODULATION OF CISPLATIN FLUOROURACIL CHEMOTHERAPY BY INTERFERON-ALPHA-2B IN PATIENTS WITH RECURRENT OR METASTATIC HEAD AND NECK-CANCER/

Purpose: In preclinical experiments, interferon alfa modulates the ant icancer activity of fluorouracil (5-FU) and cisplatin (CDDP), To test this effect clinically in patients with recurrent or metastatic head a nd neck cancer (RMHNC), a multicenter randomized controlled trial with CDDP and 5 FU with or without interferon alfa-2b (IFN alpha) was perf ormed. Patients and Methods: Eligible patients had histologically conf irmed RMHNC; a good performance status; measurable disease; adequate b one marrow, hepatic, and renal function; no prior chemotherapy for rec urrent or metastatic disease; only one chemotherapy regimen administer ed with previous local therapy; and a treatment-free interval of at le ast 3 months following previous local therapy Patients were randomized and stratified according to treatment center, and prior radiotherapy and chemotherapy. The treatment regimen consisted of CDDP 100 mg/m(2) on day 1 and 5-FU 1,000 mg/m(2)/d by continuous infusion for 96 hours (days 1 to 4), without (arm A) or with (arm B) IFNg alpha 3 x 10(6) U/ d subcutaneously on days 1 to 5, Cycles were repeated every 21 days. R esults: One hundred twenty-two patients were entered on each arm, The response rats (RR) was similar in both arms (arm A: complete response [CR] 10.7%, partial response [PR] 36.4%; arm B: CR 6.8%, PR 31.6%) (.7 0 < P < .50), There was no difference in median survival between the t wo arms (arm A 6.3 months v arm B 6.0 months; P =.49]. Anorexia, fever , leukopenia, and thrombocytopenia grade III to IV were significantly more frequent in the IFN alpha arm. Conclusion: Modulation of CDDP and 5-FU with IFN alpha as used in this study does not improve the RR or the median survival in patients with RMHNC, Patients on both study arm s had a poor prognosis, which indicates the need for novel therapies. (C) 1998 by American Society of Clinical Oncology.