title: A phase I study of amrubicin and fixed dose of irinotecan (CPT-11) in relapsed small cell lung cancer: Japan multinational trial organization LC0303.
abstract: OBJECTIVE
  To determine the maximum tolerated dose of amrubicin (AMR) with a fixed dose of irinotecan (CPT-11).
  
  
  METHODS
  Patients having pathologically proven small cell lung cancer (SCLC) relapsed after one or two chemotherapies, and Eastern Cooperative Oncology Group performance status of 0 to 2 were eligible for the study. CPT-11 was delivered as 50 mg/m2 on days 1 and 8, every 21 days. AMR was delivered on day 1. Doses of AMR were level 1: 80 mg/m2, level 2: 90 mg/m2, and level 3: 100 mg/m2. Dose elevation was determined using the modified continuous reassessment method. Tolerability was assessed after the first cycle. Another two cycles were conducted when disease progression or unacceptable toxicities were not observed.
  
  
  RESULTS
  Eighteen patients (mean age: 66.3 years) were enrolled. A total of 40 courses were conducted. Grade 3/4 toxicities of the first cycle were leukocytopenia: 11 (61%, grade 3/4: 8/3); neutropenia: 15 (83%, grade 3/4: 6/9); and thrombocytopenia: three (17%, grade 3/4: 2/1). Other grade 3 toxicities observed were febrile neutropenia, one; infection, three; diarrhea, one; and dyspnea, one. Dose-limiting toxicity was observed in two of six patients at level 2 (neutropenia and febrile neutropenia) and in one of six at level 3 (thrombocytopenia and infection). The maximum tolerated dose was level 3, and so, the recommended dose for phase II trials was judged to be 90 mg/m2. Objective response was obtained in four of eight patients who were able to evaluate responses. Median survival time was 13 months, with 68% at 1-year survival rate.
  
  
  CONCLUSIONS
  This combination was well tolerated and showed encouraging activities in SCLC. Randomized phase II trials are being planned in chemonaive SCLC.
authors.affiliation: Department of Medical Oncology, Federation of National Public Service Personnel Mutual Aid Associations, Osaka.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kawahara
authors.affiliation: Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi.
authors.forename: Akihito
authors.initials: A
authors.lastname: Kubo
authors.affiliation: Department of Respiratory Medicine, Osaka Police Hospital, Kitayama-cho, Tennoji-ku, Osaka.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Komuta
authors.affiliation: Department of Respiratory Medicine, Dohoku National Hospital, Hanasaki-cho, Asahikawa.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Internal Medicine, Osaka Kouseinennkinn Hospital, Fukushima, Osaka.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Translational Research Informatics Center Foundation for Biomedical Research and Innovation, Minatojima-minamimachi, chuo-ku Kobe.
authors.forename: Masanori
authors.initials: M
authors.lastname: Fukushima
authors.affiliation: Department of Biostatistics, Hyogo College of Medicine, Mugokagawa, Nishinomiya.
authors.forename: Takashi
authors.initials: T
authors.lastname: Daimon
authors.affiliation: The Japan Multinational Trial Organisation, Uehonnojimae-cho, Teramachi-Oike agaru, Nakagyo-ku, Kyoto.
authors.forename: Kiyoyuki
authors.initials: K
authors.lastname: Furuse
authors.affiliation: Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
authors.affiliation: Department of Multidisciplinary Cancer Treatment, Kyoto University Graduate School of Medicine, Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan.. Electronic address: mio@kuhp.kyoto-u.ac.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Mio
mesh_terms: D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007390:International Agencies; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
chemical_list: D018943:Anthracyclines; D000077146:Irinotecan; C055866:amrubicin; D002166:Camptothecin