First clinical pharmacokinetic dose-escalation study of sagopilone, a novel, fully synthetic epothilone, in Japanese patients with refractory solid tumors

Invest New Drugs. 2012 Dec;30(6):2327-33. doi: 10.1007/s10637-011-9773-7. Epub 2011 Dec 4.

Abstract

Purpose: 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.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics*
  • Area Under Curve
  • Asian People
  • Benzothiazoles / administration & dosage
  • Benzothiazoles / blood
  • Benzothiazoles / pharmacokinetics*
  • Drug Administration Schedule
  • Epothilones / administration & dosage
  • Epothilones / blood
  • Epothilones / pharmacokinetics*
  • Female
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Benzothiazoles
  • Epothilones
  • sagopilone