COMBINED-MODALITY TREATMENT OF SMALL-CELL LUNG-CANCER - RANDOMIZED COMPARISON OF 3 INDUCTION CHEMOTHERAPIES FOLLOWED BY MAINTENANCE CHEMOTHERAPY WITH OR WITHOUT RADIOTHERAPY TO THE CHEST

Background: From 1980 to 1983 the Swiss Group for Clinical Cancer Rese arch (SAKK) performed a randomised phase III trial in patients with sm all-cell lung cancer with the objective of improving the results of in duction chemotherapy and defining the role of consolidating chest irra diation. Patients and methods: Patients were initially randomised to i nduction arms AVP (adriamycin, etoposide and cisplatin given every fou r weeks for four cycles), EVA (cyclophosphamide, etoposide and adriamy cin given every four weeks for four cycles) or MOC/AVP (methotrexate, vincristine, cyclophosphamide alternating with adriamycin, etoposide a nd cisplatin given. for two cycles). All patients received prophylacti c cranial irradiation with 30 Gy, and after four months of induction c hemotherapy were randomized to maintenance chemotherapy with or withou t consolidating chest irradiation. The patients in the combined-modali ty maintenance arm first received radiation therapy to the chest (45 G y) followed by MOC/EVA chemotherapy. Results: 266 patients were eligib le and evaluable. An overall response rare of 70% with 21% of complete remissions, a median survival of 9.3 months and survival of 8% of the patients at two years were observed. The highest objective response r ate was achieved with the AVP-induction chemotherapy with an 80% respo nse rate and 32% complete remissions. Similar results were achieved wi th the alternating regimen of MOC/AVP. In contrast, patients treated w ith the EVA induction regimen had significantly lower overall remissio n (56%) and complete remission rates (7%). The role of consolidating c hest irradiation could not be clarified in limited-disease patients du e to the small number of them who were randomised to the maintenance p art of the study. However,in patients with extensive disease in partia l remission after induction treatment, combined maintenance therapy ha d a more significant adverse effect on survival than maintenance chemo therapy alone (median survival in the maintenance phase of 148 days ve rsus 239 days, p = 0.011). Conclusion: We conclude that the combinatio n of adriamycin, etoposide and cisplatin is an active induction treatm ent. Consolidating chest irradiation is contraindicated in patients wi th extensive disease in partial remission after induction when given i n a sequential manner, as in our trial.