EARLY VERSUS LATE ALTERNATING CHEMOTHERAPY IN SMALL-CELL LUNG-CANCER

Background: From 1984 to 1989, the Swiss Group for Clinical Cancer Res earch (SAKK) performed a randomized phase III trial comparing early ve rsus late alternating chemotherapy in patients with small-cell lung ca ncer. Patients and methods: 406 eligible patients were entered into th e trial. Regimen A consisted of PAY (cisPlatin, Adriamycin, VP 16-213, and Regimen B of CyMOC (Cyclophosphamide, Methotrexate, Oncovin, CCNU ). Cycles were repeated as rapidly as possible. Patients were randomiz ed to receive either ABABAB (early alternating chemotherapy) or AAABBB (late alternating chemotherapy). After six cycles patients with limit ed disease in complete or partial remission and those with extensive d isease in complete remission received irradiation to the primary (45 G y) and the CNS (36 Gy). Results: The overall remission rate was 87%, w ith 31% complete remissions. The median survival of all 406 eligible p atients was 346 days, with 15% of the patients alive at two years. The overall remission rate, the rate of complete remission,the median sur vival and the rate of long-term survival were not significantly differ ent in the two treatment arms. In limited disease the estimated percen tages of survival at 2 years were 33% in the early and 24% in the late alternating chemotherapy arms. Patients with extensive disease surviv ed significantly longer with late alternating chemotherapy than on the early alternation regimen (median survival 336 days versus 301 days, p = 0.01). In the latter patients the received dose intensities (RDI) of cisplatin, adriamycin and etoposide were significantly higher in th e late-altercation arm. Patients treated with early alternating chemot herapy rated their tumor symptoms, functional states, fatigue/malaise and restriction of social activity significantly better, reflecting an improved subjective adjustment. Conclusions: Alternating chemotherapy with PAV-Cy- MOC plus consolidating radiotherapy is a feasible and ef fective treatment for small-cell lung cancer, with acceptable toxicity . Whereas patients with early alternating chemotherapy achieve a bette r subjective adjustment, late alternating chemotherapy allows for a hi gher RDI of cisplatin, adriamycin and etoposide, which results in a si gnificantly longer median survival of patients with extensive disease.