title: Phase I study of amrubicin and vinorelbine in non-small cell lung cancer previously treated with platinum-based chemotherapy.
abstract: BACKGROUND
  Combination chemotherapy comprising amrubicin and vinorelbine as a second-line therapy for advanced non-small cell lung cancer (NSCLC) has not been fully evaluated. To determine the maximum tolerated dose (MTD) and recommended dose (RD), the present phase I study examined patients with advanced NSCLC.
  
  
  METHODS
  The subjects were nine patients with histologically confirmed advanced NSCLC, Eastern Cooperative Oncology Group performance status 0-1, prior platinum-based first-line chemotherapy, and measurable or evaluable lesions. Treatment consisted of five dose levels, with amrubicin 35-45 mg/m2 administered as a 5-min intravenous infusion on days 1-3 and vinorelbine 15-25 mg/m2 given as a 1-h intravenous infusion on days 1 and 8, every 3 weeks.
  
  
  RESULTS
  All patients had received carboplatin and paclitaxel as first-line therapy. Dose-limiting toxicity (DLT) was seen in two of six patients (febrile neutropenia and deep vein thrombosis ) at level 1, allowing us to conduct level 2. At level 2, all three patients experienced DLT (leucopenia > or =4 days in one patient; febrile neutropenia in three patients; and infection in two patients), and this level was determined as the MTD. Subsequently, level 1 (amrubicin 35 mg/m2 and vinorelbine 15 mg/m2) was defined as the RD. Responses in the nine patients included a partial response in one patient and stable disease in four patients.
  
  
  CONCLUSIONS
  As second-line therapy, the RD of the combination of amrubicin and vinorelbine is 35 mg/m2 and 15 mg/m2, respectively. Further study should proceed to clarify the efficacy of this regimen.
authors.affiliation: First Department of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan. soizumi@med.hokudai.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Oizumi
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokouchi
authors.forename: Jun
authors.initials: J
authors.lastname: Konishi
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Hommura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kojima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Isobe
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D018943:Anthracyclines; D014747:Vinblastine; C055866:amrubicin; D016190:Carboplatin; D017239:Paclitaxel; D000077235:Vinorelbine