One hundred and forty-five patients with limited stage
small cell lung cancer were included in a randomized trial to evaluate the effect of
chemotherapy with or without chest irradiation. Seventy-six patients were allotted
chemotherapy alone while 69 patients received the same
chemotherapy plus
radiotherapy, 40 Gy in split-course, administered in weeks 6 and 10 after the initiation of
chemotherapy. The
chemotherapy consisted of
lomustine,
cyclophosphamide,
vincristine and
methotrexate. Patients treated with
chemotherapy alone survived for a median of 52 weeks compared to 44 weeks in patients receiving the combined regimen (P = 0.055). After exclusion of five early deaths and one patient refusing the irradiation plus 14 completely resected patients, the remaining 65 patients receiving
chemotherapy alone and the 60 patients treated with
chemotherapy plus
radiotherapy were included in a new analysis. The difference in survival duration which could be ascribed to treatment with or without chest irradiation thereby diminished (P = 0.24). Eighteen months' disease-free survival was obtained in 9.2% of the 65 patients and in 9.8% of the 60 patients. The complete remission rates were 37% and 46%, respectively, (P = 0.33) and the median durations of complete remission were 40 weeks and 52 weeks (P = 0.67). Treatment failure of the primary tumour occurred in 85% of patients treated with
chemotherapy alone in contrast to 61% of patients receiving the combined regimen (P = 0.005). Seventy-nine of these patients underwent autopsy at which no residual chest disease was observed in 17% and 37%, respectively (P = 0.045). The combined regimen was more toxic than
chemotherapy alone resulting in significantly greater
dose reductions and more pronounced
thrombocytopenia. Lung and pericardial
fibrosis was responsible for four deaths among the complete responders in the
radiotherapy group. The combined regimen thus tended to be more efficacious with respect to tumour control at the expense, however, of increased toxicity which per se, eliminated a potential improvement of the overall therapeutical results.