INTERLEUKIN-2 ACTIVITY IN PATIENTS WITH EXTENSIVE SMALL-CELL LUNG-CANCER - A PHASE-II TRIAL OF CANCER AND LEUKEMIA GROUP-B

Background: Chemotherapy may induce overall (complete plus partial) response rates of more than 50% and complete response rates up to 25% in extensive small-cell lung cancer (stage IIIB or IV), but survival is generally limited to 8-12 months. Interleukin-2 (IL-2) has demonstrated activity against this disease in vitro and has produced regression in melanoma and renal cell carcinoma. Purpose: The purpose of this study was to determine in a prospective. nonblinded, phase II trial the activity of IL-2 in patients with extensive small-cell lung cancer who had not achieved complete remission with chemotherapy. Methods: The 68 patients eligible for the study were initially treated with at least one dose of combination chemotherapy with cisplatin, doxorubicin, cyclophosphamide, and etoposide (PACE). Of the 50 who did not obtain complete remission with PACE, 24 who had measurable or evaluable disease and whose medical condition allowed further therapy were treated with IL-2. Beginning 3 weeks after the last dose of PACE, IL-2 was administered intravenously at 4.5 million Nutley units/m2 per day as a continuous infusion for 96 hours, followed by a 3-day rest. The planned duration of therapy was 8 weeks. Results: Of the 24 patients eligible to receive IL-2, four (17%) with measurable disease or evaluable but not measurable disease obtained a complete response after IL-2 therapy; one (4%) patient had a partial response. The overall response rate was 21%. Complete responses continued for 8, 9, and more than 11 months in three patients; the remaining patient developed acute myelomonocytic leukemia while in complete remission approximately 8 months after the start of IL-2 therapy. Only five of the 24 patients were able to complete the planned 8 weeks of IL-2 therapy. Therapy was discontinued in 11 patients because of life-threatening side effects, in six because of disease progression, and in two who with-drew from the study, probably related to IL-2 toxicity. Conclusions: These results indicate that IL-2 has some activity in extensive small-cell lung cancer and suggest that IL-2 is not cross-resistant with PACE therapy. Implications: Further studies are needed to define the optimum timing, dose, and schedule of IL-2 and to determine whether the agent has a role in the therapy of small-cell lung cancer.