Randomized phase II-III trial of combination beta and gamma interferons and etoposide and cisplatin in inoperable non-small cell cancer of the lung

We observed major responses in two patients with adenocarcinoma of the lung who had received a combination of interferon (IFN)-β and IFN-γ, immediately followed by chemotherapy. To verify these observations, we initiated a prospective randomized phase II-III trial of etoposide and cisplatin, with or without IFN-β and IFN-γ, in patients with inoperable non-small cell lung cancer. Thirty-seven patients were randomized to receive either two cycles of chemotherapy or 6 weeks of IFN-β plus IFN-γ followed by two cycles of chemotherapy. Chemotherapy consisted of 60 mg of cisplation/m² on day 1 and 120 mg of etoposide/m² on days 4, 6, and 8, repeated every 21 days. Patients who were randomized to the IFN plus chemotherapy arm received 200 μg of IFN-γ and 30 × 10⁶ U of IFN-β three times per week for 6 weeks, followed by two cycles of chemotherapy. Three of 18 (17%) eligible patients in the chemotherapy arm and two of 18 (11%) patients in the combination arm had partial responses. All responses occurred while patients were receiving chemotherapy. Median survival was 190 days for the chemotherapy arm and 246 days in the combined modality arm, as estimated from Kaplan-Meier curves (P = .35). We observed no significant difference in subjective toxic effects between the two arms. We observed more hematologic toxicity during chemotherapy on the combined modality arm (P = .02). We conclude that pretreatment with IFN-β and IFN-γ does not enhance the efficacy of etoposide and cisplatin in this disease. Although the combined modality arm is relatively well tolerated, it does result in more chemotherapy-associated toxic effects. This study also exemplifies a hybrid phase II-III trial design, which is useful in allowing phase II results to be quickly incorporated into a phase III trial. [J Natl Cancer Inst 81:1739-1743, 1989]