title: A phase II study of amrubicin and topotecan combination therapy in patients with relapsed or extensive-disease small-cell lung cancer: Okayama Lung Cancer Study Group Trial 0401.
abstract: BACKGROUND
  Chemotherapy is a mainstay in the treatment of extensive-disease small-cell lung cancer (ED-SCLC), although the survival benefit remains modest. We conducted a phase II trial of amrubicin (a topoisomerase II inhibitor) and topotecan (a topoisomerase I inhibitor) in chemotherapy-naïve and relapsed SCLC patients.
  
  
  METHODS
  Amrubicin (35 mg/m(2)) and topotecan (0.75 mg/m(2)) were administered on days 3-5 and 1-5, respectively. The objective response rate (ORR) was set as the primary endpoint, which was assessed separately in chemotherapy-naïve and relapsed cases.
  
  
  RESULTS
  Fifty-nine patients were enrolled (chemotherapy-naïve 31, relapsed 28). The ORRs were 74% and 43% in the chemotherapy-naïve and relapsed cases, respectively. Survival data were also promising, with a median progression-free survival time and median survival time of 5.3 and 14.9 months and 4.7 and 10.2 months in the chemotherapy-naïve and relapsed cases, respectively. Even refractory-relapsed cases responded to the treatment favorably (27% ORR). The primary toxicity was myelosuppression with grades 3 or 4 neutropenia in 97% of the patients, which led to grades 3 or 4 febrile neutropenia in 41% of the patients and two toxic deaths.
  
  
  CONCLUSIONS
  This phase II study showed the favorable efficacy and moderate safety profiles of a topotecan and amrubicin two-drug combination especially in relapsed patients with ED-SCLC.
authors.affiliation: Department of Respiratory Medicine, NHO Shikoku Cancer Center, Matsuyama, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Nogami
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kuyama
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Chikamori
authors.forename: Takuo
authors.initials: T
authors.lastname: Shibayama
authors.forename: Daizo
authors.initials: D
authors.lastname: Kishino
authors.forename: Shinobu
authors.initials: S
authors.lastname: Hosokawa
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tamaoki
authors.forename: Shingo
authors.initials: S
authors.lastname: Harita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueoka
authors.forename: Tetsu
authors.initials: T
authors.lastname: Shinkai
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology; D012008:Recurrence; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D016019:Survival Analysis; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D019772:Topotecan; C055866:amrubicin