title: Standard versus dose-intensified chemotherapy with sequential reinfusion of hematopoietic progenitor cells in small cell lung cancer patients with favorable prognosis.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Patients receiving ICT with filgrastim achieved significant increases in median survival and TTP despite an increased need for transfusions.
authors.affiliation: Department of Surgery and Interdisciplinary Thoracic Oncology, Klinikum Mannheim, Mannheim, Germany. erika-buchholz@t-online.de
authors.forename: Erika
authors.initials: E
authors.lastname: Buchholz
authors.forename: Christian
authors.initials: C
authors.lastname: Manegold
authors.forename: Lothar
authors.initials: L
authors.lastname: Pilz
authors.forename: Nick
authors.initials: N
authors.lastname: Thatcher
authors.forename: Peter
authors.initials: P
authors.lastname: Drings
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018288:Carcinoma, Small Cell / Q000401:mortality / Q000628:therapy*; D003131:Combined Modality Therapy; D018450:Disease Progression; D017707:Erythrocyte Transfusion; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008175:Lung Neoplasms / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D017713:Platelet Transfusion; D011379:Prognosis; D011994:Recombinant Proteins; D015996:Survival Rate
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D016190:Carboplatin; D000069585:Filgrastim; D007069:Ifosfamide