title: First clinical pharmacokinetic dose-escalation study of sagopilone, a novel, fully synthetic epothilone, in Japanese patients with refractory solid tumors.
abstract: OBJECTIVE
  Sagopilone has recently been identified and preferentially used for the treatment of taxane-resistant cancer. The purpose of this dose-escalation study was to investigate the safety, tolerability, and pharmacokinetics (PK) of sagopilone in refractory solid tumors.
  
  
  METHODS
  A total of 17 Japanese patients received sagopilone in this Phase I study. Sagopilone was given as a 30-min intravenous infusion once every 3 weeks (one course) with an initial dose of 12.4 mg/m(2) up to 22.0 mg/m(2) for a maximum of 6 courses.
  
  
  RESULTS
  The maximum tolerated dose (MTD) was determined to be 16.5 mg/m(2). The major dose-limiting toxicity (DLT) was peripheral sensory neuropathy. The PK data demonstrated that sagopilone did not accumulate after repeated administration. Two patients had stable disease (SD) over a period of 12 weeks.
  
  
  CONCLUSIONS
  Our study demonstrated clinically favorable safety, tolerability, and efficacy of sagopilone, which will help define the treatment of advanced tumors in more extensive clinical trials.
authors.affiliation: Department of Clinical Oncology, Saitama Medical University, Saitama, Japan. kaaraki@saitama-med.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Araki
authors.forename: Koichi
authors.initials: K
authors.lastname: Kitagawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mukai
authors.forename: Toru
authors.initials: T
authors.lastname: Mukohara
authors.forename: Keiji
authors.initials: K
authors.lastname: Kodama
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ando
authors.forename: Masaru
authors.initials: M
authors.lastname: Narabayashi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Minami
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Mera
authors.forename: Yasutsuna
authors.initials: Y
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D052160:Benzothiazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D034261:Epothilones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; D034261:Epothilones; C530494:sagopilone