Early versus late alternating chemotherapy in small-cell lung cancer

BACKGROUND: From 1984 to 1989, the Swiss Group for Clinical Cancer Research(SAKK) performed a randomized phase 111 trial comparing earlyversus late alternating chemotherapy in patients with small-celllung cancer. PATIENTS AND METHODS: 406 eligible patients were entered into the trial. Regimen Aconsisted of PAV(cisPlatin, Adriamycin, VP 16–213, andRegimen B of CyMOC (Cyclophosphamide, Methotrexate, Oncovin,CCNU). Cycles were repeated as rapidly as possible. Patientswere randomized to receive either ABABAB (early alternatingchemotherapy) or AAABBB (late alternating chemotherapy). Aftersix cycles patients with limited disease in complete or partialremission and those with extensive disease in complete remissionreceived irradiation to the primary (45 Gy) and the CNS (36Gy). RESULTS: The overall remission rate was 87%, with 31% complete remissions.The median survival of all 406 eligible patients was 346 days,with 15% of the patients alive at two years. The overall remissionrate, the rate of complete remission, the median survival andthe rate of long-term survival were not significantly differentin the two treatment arms. In limited disease the estimatedpercentages of survival at 2 years were 33% in the early and24% in the late alternating chemotherapy arms. Patients withextensive disease survived significantly longer with late alternatingchemotherapy than on the early alternation regimen (median survival336 days versus 301 days, p=0.01). In the latter patients thereceived dose intensities (RD1) of cisplatin, adriamycin andetoposide were significantly higher in the late-alternationarm. Patients treated with early alternating chemotherapy ratedtheir tumor symptoms, functional states, fatigue/malaise andrestriction of social activity significantly better, reflectingan improved subjective adjustment. CONCLUSIONS: Alternating chemotherapy with PAV-Cy-MOC plus consolidatingradiotherapy is a feasible and effective treatment for small-celllung cancer, with acceptable toxicity. Whereas patnts with earlyalternating chemotherapy achieve a better subjective adjustment,late alternating chemotherapy allows for a higher RDI of cisplatin,adriamycin and etoposide, which results in a significantly longermedian survival of patients with extensive disease. small-cell lung cancer, chemotherapy, alternating chemotherapy, quality of life, dose intensity