LONG-TERM RESULTS OF A PHASE I II STUDY OF AGGRESSIVE CHEMOTHERAPY AND SEQUENTIAL UPPER AND LOWER HEMIBODY RADIATION FOR PATIENTS WITH EXTENSIVE-STAGE SMALL-CELL LUNG-CANCER/

Background. A Phase I/II study of an aggressive six-drug chemotherapy regimen followed by the use of sequential hemibody radiation therapy a s a possible non-cross-resistant systemic treatment was undertaken for patients with extensive stage small cell lung cancer. Methods. The 20 enrolled patients received 7 cycles of cyclophosphamide-based chemoth erapy. The first cycle consisted of cyclophosphamide, doxorubicin, eto poside, vincristine, and lomustine. Subsequent cycles used a regimen o f doxorubicin alternating with cisplatin. Thoracic radiation was deliv ered in a split-course fashion during the first week of chemotherapy c ycles 5 and 6 (2000 cGy in five fractions during each week). Prophylac tic cranial radiation was delivered in a split-course fashion during t he first week of chemotherapy cycles 2 and 3 (1700 cGy in 5 fractions during each week). After the 7 cycles, patients received 600 cGy upper hemibody radiation followed by 800 cGy lower hemibody radiation. Resu lts. Nineteen of 20 patients were evaluable for toxicity and response to treatment. Hematologic toxicity accounted for treatment delays or d ecreased doses in 16 of 19 patients. Thirteen patients completed the i nitial 7 cycles; progressive disease was the only reason for discontin uing treatment. Two patients had fatal hematologic complications after lower hemibody radiation. Three patients had severe or greater periph eral neurologic toxicity, two had severe central neurologic toxicity, and one had severe cardiac toxicity. Of 19 patients, 9 achieved a comp lete response; median survival was 11.5 months. Five-year progression free survival and 5-year overall survival were 27% and 16%, respective ly. Conclusions. This aggressive regimen is feasible for patients with extensive stage small cell lung cancer; however, hematologic-related mortality after lower hemibody radiation suggests that future investig ations should be initiated at lower initial doses of lower hemibody ra diation. Long term survival of the patients suggests that sequential h emibody radiation treatment warrants further investigation.