Standard Versus Dose-Intensified Chemotherapy With Sequential Reinfusion Of Hematopoietic Progenitor Cells In Small Cell Lung Cancer Patients With Favorable Prognosis

Purpose: The combination of ifosfamide, carboplatin, and etoposide (ICE) is highly effective in treating small cell lung cancer (SCLC). Myelosuppression resulting in leukopenia and thrombocytopenia is the dose-limiting toxicity.Patients and Methods: This phase 3 study assessed 2-year survival improvement with dose intensification of ICE chemotherapy (ICT) in patients with good-prognosis SCLC. Patients received up to six cycles of ICT with filgrastim-supported sequential reinfusion of peripheral blood progenitor cells every 14 days, or standard ICE (SCT) every 28 days.Results: Eighty-three patients were randomized to ICT (n = 42) or SCT (n = 41). Median survival was significantly improved with ICT (30.3 mo) versus SCT (18.5 mo; p = 0.001); 2-year survival was 55% for ICT and 39% for SCT (p = 0.151). Time to progression (TTP) was significantly improved, with 15 months for ICT versus 11.1 months for SCT (p = 0.0001). Overall response rates were 100 and 88% for ICT and SCT, respectively (p = 0.0258). SCT was associated with significantly less grade 3 and 4 leukopenia at day 8 (p < 0.0001), less thrombocytopenia at day 14 (p < 0.0001), and more favorable platelet nadir (p < 0.0001). The need for platelet and red blood cell transfusions significantly increased in the ICT group (p < 0.0001). Nonhematologic adverse events in both groups were comparable and mostly grade 1 or 2.Conclusion: Patients receiving ICT with filgrastim achieved significant increases in median survival and TTP despite an increased need for transfusions.