ALTERNATING RADIOTHERAPY AND CHEMOTHERAPY FOR INOPERABLE STAGE-III NON-SMALL-CELL LUNG-CANCER - LONG-TERM RESULTS OF 2 PHASE-II GOTHA TRIALS

Purpose/Objective: To report on two consecutive Phase II cooperative t rials in which we evaluated the combination of alternating hyperfracti onated accelerated radiotherapy and cisplatin-based chemotherapy in in operable Stage III non-small cell lung cancer (NSCLC). Patients & Meth ods: Between February 1986 and September 1989, 65 patients were entere d in the first trial (GOTHA I), and between December 1989 and October 1992 67 were enrolled in the second trial (GOTHA II). In both protocol s, radiotherapy (RT) was administered twice daily, at 6 h intervals, 5 days a week, to a total dose of 63 Gy in 42 fractions of 1.5 Gy. RT w as given during weeks 2, 3, 6, and 7, over an elapsed time of 6 weeks. In GOTHA I, three cycles of cisplatin, 60 mg/m(2) day 1, mitomycin, 8 mg/m(2) day 1, and vindesin 3 mg/m(2) day 1 and the first day of the following week, were given during weeks 1, 5, and 9; in GOTHA II, cisp latin 70 mg/m(2) day 1 and vinblastin 5 mg/m(2) day 1 and the first da y of the following week were given during weeks 1, 5, 9, 13, 17, and 2 1. Results: With a minimum follow-up of 3 years, the 1-, 2-, 5-, and 8 -year overall survival probability was 56% (95% CI 37-64%), 27% (20-35 %), 12% (7-18%) and 9% (3-16%), respectively, with a median survival o f 13.6 months (11.4-16.8). Median follow-up for survivors was 6 years (3.3-9.9). There were no survival differences between Stages IIIA and LW (p = 0.84), performance status 0, 1, 2 (p = 0.87), sex (p = 0.45) o r between the two treatment protocols. At this time, 14 patients are a live, and 118 have died: 102 from NSCLC, 4 from acute toxicity, 2 from secondary surgery, 4 from other medical causes, and 6 from unknown ca uses. Correlation between response and long-term survival was poor, si nce of the 24 patients who survived 3 years or more, only 6 (25%) were classified as having a complete response; the remainder having either a partial response (11, 46%), no change (6, 25%), or ''progressive di sease'' (1, 4%). First site of relapse was local in 31% of these cases , distant in 43%, local and distant in 15%, and unknown in 11%. Main g rade 3-4 acute toxicities were nausea-vomiting (17%), mucositis (15%), leukopenia (41%), and thrombocytopenia (11%). Eight patients presente d with grade 3-4 symptomatic lung radiation pneumopathy. Conclusion: B ased on this experience with 132 patients, this combination of alterna ted RT and chemotherapy (CT) for inoperable Stage III NSCLC is feasibl e with acceptable toxicity, and long-term results suggest a gain in su rvival when compared to those obtained with conventional RT alone. How ever, the still high local and distant failure rates indicate that bot h local and systemic therapies need to be improved. (C) 1998 Elsevier Science Inc.