title: Phase I/II study of amrubicin, a novel 9-aminoanthracycline, in patients with advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  Amrubicin is a novel, totally synthetic 9-aminoanthracycline. The present phase I/II study was performed to define its maximum-tolerated dose (MTD), efficacy and toxicity in the treatment of previously untreated patients with advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Chemonaive patients were required to have cytologically or histologically proven measurable NSCLC, an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and adequate organ functions. Amrubicin was administered by daily intravenous injection for 3 consecutive days every 3 weeks.
  
  
  RESULTS
  In a phase I study, four patients were enrolled at dose level 1 (40 mg/m(2)/day) and four at dose level 2 (45 mg/m(2)/day). No dose limiting toxicity (DLT), which was defined as toxicity consisting of grade 4 neutropenia and leukopenia lasting four days or more, and grade 3 or 4 toxicity other than neutropenia, leukopenia, anorexia, nausea/vomiting, and alopecia, was observed at these dose levels. Subsequently, at dose level 3 (50 mg/m(2)/day), 3 of 5 patients experienced DLTs (leukopenia, neutropenia, thrombocytopenia, or gastrointestinal complications). The MTD and recommended dose (RD) were determined to be 50 mg/m(2)/day and 45 mg/m(2)/day, respectively. Three partial responses (PRs) were achieved in 13 patients (response rate, 23.1%) in a phase I study. In a phase II study, 15 patients were assessable for efficacy and toxicity at the RD, and four PRs were obtained (response rate, 26.7%). The major toxicities were leukopenia and neutropenia, while non-hematologic toxicities were mild. The overall response rate in the combined patient population of the phase I/II study was 25.0% (7 PRs in 28 patients), with a 95% confidence interval of 10.7% to 44.9%.
  
  
  CONCLUSIONS
  Amrubicin exerted promising antitumor activity on NSCLC with acceptable toxicity.
authors: Internal Medicine, Aichi Cancer Center, Nagoya, Japan. tsugiura@tea.ocn.ne.jp
authors: Takahiko
authors: T
authors: Sugiura
authors: Yutaka
authors: Y
authors: Ariyoshi
authors: Shunichi
authors: S
authors: Negoro
authors: Shinichiro
authors: S
authors: Nakamura
authors: Harumichi
authors: H
authors: Ikegami
authors: Minoru
authors: M
authors: Takada
authors: Takashi
authors: T
authors: Yana
authors: Masahiro
authors: M
authors: Fukuoka
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D016019:Survival Analysis; D059005:Topoisomerase II Inhibitors
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D059005:Topoisomerase II Inhibitors; C055866:amrubicin