Combined-modality treatment of small-cell lung cancer: Randomized comparison of three induction chemotherapies followed by maintenance chemotherapy with or without radiotherapy to the chest

BACKGROUND: From 1980 to 1983 the Swiss Group for Clinical Cancer Research(SAKK) performed a randomised phase HI trial in patients withsmall-cell lung cancer with the objective of improving the resultsof induction chemotherapy and defining the role of consolidatingchest irradiation. PATIENTS AND METHODS: Patients were initially randomised to induction arms AVP (adriamycin,etoposide and cisplatin given every four weeks for four cycles),EVA (cyclophospha-mide, etoposide and adriamycin given everyfour weeks for four cycles) or MOC/AVP (methotrexate, vincristine,cyclo-phosphamide alternating with adriamycin, etoposide andcisplatin given for two cycles). All patients received prophylacticcranial irradiation with 30 Gy, and after four months of inductionchemotherapy were randomized to maintenance chemotherapy withor without consolidating chest irradiation. The patients inthe combined-modality maintenance arm first received radiationtherapy to the chest (45 Gy) followed by MOC/EVA chemotherapy. RESULTS: 266 patients were eligible and evaluable. An overall responserate of 70% with 21% of complete remissions, a median survivalof 9.3 months and survival of 8% of the patients at two yearswere observed. The highest objective response rate was achievedwith the AVP-induction chemotherapy with an 80% response rateand 32% complete remissions. Similar results were achieved withthe alternating regimen of MOC/AVP. In contrast, patients treatedwith the EVA induction regimen had significantly lower overallremission (56%) and complete remission rates (7%). The roleof consolidating chest irradiation could not be clarified inlimited-disease patients due to the small number of them whowere randomised to the maintenance part of the study. However,in patients with extensive disease in partial remission afterinduction treatment, combined maintenance therapy had a moresignificant adverse effect on survival than maintenance chemotherapyalone (median survival in the maintenance phase of 148 daysversus 239 days, p = 0.011). CONCLUSION: We conclude that the combination of adriamycin, etoposide andcisplatin is an active induction treatment. Consolidating chestirradiation is contraindicated in patients with extensive diseasein partial remission after induction when given in a sequentialmanner, as in our trial. small-cell lung cancer, chemotherapy, alternating chemotherapy, combined-modality treatment, radiotherapy