title: A phase I study of amrubicin combined with carboplatin for elderly patients with small-cell lung cancer.
abstract: BACKGROUND
  Amrubicin, a new anthracycline agent, has shown high activity for small-cell lung cancer (SCLC) with acceptable toxicities in previous studies. However, a combination regimen of platinum and amrubicin for elderly patients has not been reported. In this phase I study, the dose-limiting toxicity (DLT), the maximal tolerable dose (MTD), and the antitumor activity of a combination of amrubicin and carboplatin in elderly patients with SCLC were evaluated.
  
  
  METHODS
  Previously untreated elderly patients (> or =70 years old) with SCLC were enrolled in this study. Amrubicin was administered from day 1 to day 3, and carboplatin was administered on day 1 intravenously. The treatment was repeated every 3 weeks. Three escalating dose levels of amrubicin (mg/m)/carboplatin (area under the curve; AUC) (40/4.0, 40/5.0, and 45/5.0) were initially planned.
  
  
  RESULTS
  Twelve patients were enrolled. At level 1 (amrubicin 40 mg/m and carboplatin AUC 4.0), all three patients experienced DLTs (grade 4 neutropenia > or =4 days, thrombocytopenia <20,000/mm, or grade 3 diarrhea), and this dose level was determined to be the MTD. At the reduced dose of level 0 (amrubicin 35 mg/m and carboplatin AUC 4.0), although DLTs were observed in three of the nine patients, they were considered to be clinically not severe and could be managed. Non-hematological toxicities were mild or moderate and reversible. The objective response rate was 83%, and the median survival time was 12.7 months.
  
  
  CONCLUSIONS
  The MTD of this combination was amrubicin 40 mg/m and carboplatin AUC 4.0, and the recommended dose for a phase II trial is a combination of amrubicin 35 mg/m and carboplatin AUC 4.0. We are now conducting a multicenter phase II trial of this regimen to determine the activity of this combination for elderly patients with SCLC.
authors.affiliation: Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan. akinoue@idac.tohoku.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Inoue
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Maemondo
authors.forename: Takuji
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kimura
authors.forename: Mariko
authors.initials: M
authors.lastname: Kanbe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Isobe
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Saijo
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D009367:Neoplasm Staging; D018579:Patient Selection; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; C055866:amrubicin; D016190:Carboplatin