Standard versus Dose-Intensified Chemotherapy with Sequential Reinfusion of Hematopoietic Progenitor Cells in Small Cell Lung Cancer Patients with Favorable Prognosis

• Published in: Journal of thoracic oncology 2007-01, Vol.2 (1), p.51-58
• Main Authors: Buchholz, Erika, Manegold, Christian, Pilz, Lothar, Thatcher, Nick, Drings, Peter
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin - administration & dosage; Carboplatin - adverse effects; Carcinoma, Small Cell - mortality; Carcinoma, Small Cell - therapy; Chemotherapy; Combined Modality Therapy; Disease Progression; Erythrocyte Transfusion; Etoposide - administration & dosage; Etoposide - adverse effects; Female; Filgrastim; Granulocyte Colony-Stimulating Factor - administration & dosage; Hematopoietic progenitor cells; Hematopoietic Stem Cell Transplantation; Humans; ICE; Ifosfamide - administration & dosage; Ifosfamide - adverse effects; Lung Neoplasms - mortality; Lung Neoplasms - therapy; Male; Middle Aged; Platelet Transfusion; Prognosis; Recombinant Proteins; Small cell lung cancer; Survival Rate
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1097/JTO.0b013e31802baf9d

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. 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. 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. Patients receiving ICT with filgrastim achieved significant increases in median survival and TTP despite an increased need for transfusions.