title: Phase I and pharmacologic study of weekly amrubicin in patients with refractory or relapsed lung cancer: Central Japan Lung Study Group (CJLSG) 0601 trial.
abstract: OBJECTIVE
  To evaluate the safety and tolerability of amrubicin (AMR), determine its maximum tolerated dose (MTD), its dose-limiting toxicities (DLTs), and its recommended dose (RD), and to conduct a pharmacokinetic study of weekly AMR administrations in patients with chemotherapy-refractory or recurrent small cell or non-small cell lung cancer.
  
  
  METHODS
  Patients with refractory or relapsed non-small cell and small cell lung cancer after 1 or 2 regimens of chemotherapy were eligible. AMR was initiated at 45 mg/m(2) weekly (repetition of dose on 1st and 8th day with a rest on day 15). The dose level was increased by 5 mg/m(2) by modified Fibonacci dose escalation scheme.
  
  
  RESULTS
  Seven patients had small cell lung cancer and 9 had non-small cell lung cancer. Fifty-four courses (median: 3, range: 1-6) were administered at 5 dose levels. At 65 mg/m(2), 3 patients had DLTs as follows: 1 was grade 3 (CTCAE v3.0) in AST/ALT, 1 was grade 3 febrile neutropenia, and 1 was grade 4 neutropenia. Leukocytopenia and neutropenia were correlated with amrubicinol (AMR-OH) C (max) (P = 0.042, P = 0.047, respectively). The AUC (area under the curve of plasma concentration versus time extrapolated to concentration zero) of AMR and AMR-OH did not depend on the dose levels.
  
  
  CONCLUSIONS
  In the present phase I study of AMR administered weekly to previously treated lung cancer patients, the maximum tolerated dose and RD were 65 and 60 mg/m(2), respectively. The best response rate was 15.4%, and adverse events with this schedule were tolerable.
authors.affiliation: Department of Medical Oncology, National Hospital Organization Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, Nagoya, Aichi 460-0001, Japan. kitagawc@nnh.hosp.go.jp
authors.forename: Chiyoe
authors.initials: C
authors.lastname: Kitagawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Saka
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Kajikawa
authors.forename: Kouki
authors.initials: K
authors.lastname: Mori
authors.forename: Masahide
authors.initials: M
authors.lastname: Oki
authors.forename: Ryujiro
authors.initials: R
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; C055866:amrubicin