RANDOMIZED TRIAL OF ALTERNATING VERSUS SEQUENTIAL RADIOTHERAPY CHEMOTHERAPY IN LIMITED-DISEASE PATIENTS WITH SMALL-CELL LUNG-CANCER - A EUROPEAN ORGANIZATION FOR RESEARCH AND TREATMENT OF CANCER LUNG-CANCER COOPERATIVE GROUP-STUDY/

Purpose: To evaluate the effectiveness of alternating or sequential sc hedules of cyclophosphamide, doxorubicin, and etoposide (CDE) chemothe rapy and irradiation in patients with previously untreated small-cell lung cancer (SCLC). Materials and Methods: A total of 335 eligible pat ients were randomized five courses of CDE chemotherapy followed by tho racic irradiation 50 Gy in 20 daily fractions (S) and the same total d ose of chemotherapy and irradiation split into four courses of five da ily fractions delivered on days 14 to 21 of the second and subsequent chemotherapy courses (A). Patients had a median age of 61 years (range , 33 to 75); 224 (66%) were male; the Eastern Cooperative Oncology Gro up (ECOG) performance status (PS) was 0 or 1 in 311; and 254 had weigh t loss less than 10%. Results: The overall median survival duration wa s 15 months, with 62% (95% confidence interval [CI], 57% to 67%) 1-yea r, 25% (95% CI, 20% to 30%) 2-year, and 14% (95% CI, 10% to 18%) 3-yea r survival rates. There was no significant difference between the arms . The median survival rime was 14 months in A and 15 months in S. One- year survival was 60% in A (95% CI, 53% to 67%) and 64% in S (95% CI, 57% to 71%); 2-year survival was 26% in A (95% CI, 19% to 33%) and 23% in S (95% CI, 16% to 30%); and 3-year survival was 12% in A (95% CI, 6% to 18%) and 15% in S (95% CI, 9% to 21%). World Health Organization (WHO) grade 3 and 4 neutropenia occurred in 90% of A and 77% of 5 pat ients (P <.001) and WHO grade 3 and 4 thrombocytopenia in 33% of A and 20% of S patients (P <.001). Rates of other acute and late toxicities were similar in both arms. Hematologic toxicity compromised treatment dose delivery; less than 50% of A patients received greater than 95% of prescribed chemotherapy and 77% their full radiation course, compar ed with 60% and 93% for arm S (P < .009). Local relapse was the site o f first failure in 60% of all patients and 75% of these suffered an in -field relapse; no difference could be seen between the two arms. Conc lusion: This trial failed to confirm the superiority of an alternating schedule of delivery. For this combination of chemotherapy and irradi ation, hematologic toxicity compromised treatment delivery and could h ave contributed to the overall result. The poor rates of local control are disappointing and require intensification of the radiation therap y strategy. (C) 1991 by American Society of Clinical Oncology.