Dose-intensive therapy in lung cancer

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Abstract
Lung cancer is epidemic and lethal throughout the world. Overall survival is estimated to be 13% at 5 years despite treatment. The use of chemotherapy in small-cell lung cancer (SCLC) is established, but it is less active against non-SCLC (NSCLC). Since 98% of SCLC cases are associated with heavy smoking and present at a median age of 60–65 years, the application of dose-intensive therapy to lung cancer patients may be complicated by underlying smoking-related comorbidity and an enhanced risk for secondary smoking-related malignancies. The strategies of intensifying induction therapy, multicycle dose-intensive combination therapies, chest radiotherapy, and stem cell purging for both SCLC and NSCLC are discussed herein. Limited data regarding high-dose therapy for NSCLC have been reported. In SCLC, excellent and immediate palliation is achieved through the use of combination chemotherapy. However, by 2 years, only 20–40% of limited-disease- (LD) and 40 patients with LD SCLC and >25 patients with ED SCLC who were in first response to conventional-dose therapy comprising high-dose combination alkylating agents. Approximately 80% of our patients were in or near complete response after initial chemotherapy. At a minimal follow-up of 23 months (to as long as 10 years) after completion of high-dose chemotherapy in our original trial, 52% of the patients remain disease-free. Of the ED or extrapulmonary patients, approximately 20% remain progression-free at >2 years after high-dose therapy. Local regional recurrence represents about 50% of all relapses. Thus, the roles of thoracic radiation dose intensity and purification of stem-cell autografts are being evaluated in ongoing trials. It is hoped that a cooperative phase III trial testing the concept of dose intensification will begin soon.

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