title: A randomized phase III study of single-agent amrubicin vs. carboplatin/etoposide in elderly patients with extensive-disease small-cell lung cancer.
abstract: BACKGROUND
  The efficacy and safety of amrubicin, a third-generation synthetic anthracycline, were evaluated by comparison with carboplatin/etoposide combination therapy in elderly Japanese patients with extensive-disease small-cell lung cancer (ED-SCLC).
  
  
  METHODS
  Eligibility included histologically or cytologically proven SCLC, no previous systemic chemotherapy, performance status of 0 to 2, and age ≥ 70 years. Patients received amrubicin (70-74 years old, 40-45 mg/m(2); ≥ 75 years old, 40 mg/m(2)) intravenously on days 1 to 3 every 3 weeks for 4 to 6 cycles or carboplatin (area under the curve of 5 intravenously on day 1) and etoposide (80 mg/m(2) intravenously on days 1 to 3) every 3 weeks for 4 to 6 cycles.
  
  
  RESULTS
  The target number of patients was 130 with 65 in each arm. However, the study was terminated early owing to 3 treatment-related deaths in the amrubicin arm, and only 62 patients (median age, 76 years; range, 70-88 years) were enrolled. The characteristics of the patients in the amrubicin and carboplatin/etoposide arms did not differ significantly. Overall survival, time to progression, and objective response rate were 10.9 vs. 11.3 months (P = .7353), 4.7 vs. 4.4 months, and 74.2% (23 of 31) vs. 60.0% (18 of 30), respectively, and quality of life showed no significant difference between the 2 arms. Higher incidences of febrile neutropenia and interstitial lung disease of grade 3 or worse occurred with amrubicin (34.4% vs. 3.3% and 12.5% vs. 0%, respectively).
  
  
  CONCLUSIONS
  These results indicate that amrubicin monotherapy at 40 to 45 mg/m(2) is toxic and intolerable in elderly Japanese patients with ED-SCLC.
authors.affiliation: National Cancer Center Hospital, Tokyo, Japan. Electronic address: isekine@chiba-u.jp.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Sekine
authors.affiliation: Yokohama Municipal Citizens' Hospital, Yokohama, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Cancer Institute Hospital Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Horai
authors.affiliation: Kinki University School of Medicine, Osakasayama, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ohmatsu
authors.affiliation: Niigata Cancer Center Hospital, Niigata, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yokoyama
authors.affiliation: Institute of Biomedical Research and Innovation Hospital, Kobe, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
authors.affiliation: Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Shibuya
authors.affiliation: National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
authors.affiliation: Kinki University School of Medicine, Osakasayama, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
mesh_terms: D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D016190:Carboplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D011788:Quality of Life; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
chemical_list: D018943:Anthracyclines; D005047:Etoposide; C055866:amrubicin; D016190:Carboplatin
keywords: Chemotherapy; Interstitial lung disease; Pulmonary disease; Pulmonary toxicity; Treatment-related death