A pediatric phase I trial and pharmacokinetic study of ispinesib: A Children's Oncology Group phase I consortium study

Abdul Kader Souid, Ronald L. Dubowy, Ashish M. Ingle, Maureen G. Conlan, Junfeng Sun, Susan M. Blaney, Peter C. Adamson

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Purpose: To determine the maximum-tolerated dose, dose-limiting toxicities, and pharmacokinetics of the kinesin spindle protein inhibitor ispinesib in pediatric patients with recurrent or refractory solid tumors. Subjects and Methods: Ispinesib was administered as 1-hr intravenous infusion weekly×3, every 28 days. Cohorts of 3-6 patients were enrolled at 5, 7, 9, and 12mg/m 2/dose. Serial plasma samples for pharmacokinetic analyses were obtained after the first dose. Results: Twenty-four (13 females) patients with a median (range) age of 10 years (1-19) were enrolled in the study. At the 12mg/m 2 dose level dose-limiting neutropenia occurred in 2/6 patients and hyperbilirubinemia in 1/6 patients, while at the 9mg/m 2 dose level 1/6 patients had dose-limiting neutropenia. There were no objective responses, but three patients (diagnoses of anaplastic astrocytoma, alveolar soft part sarcoma, and ependymoblastoma) had stable disease for 4-7 courses. There was substantial interpatient variation in drug disposition. The median (range) terminal elimination half-life was 16 (8-44)hr and the plasma drug clearance was 5 (1-14)L/hr/m 2. Conclusions: The maximum tolerated and recommended phase II dose for ispinesib administered weekly×3 every 28 days for children with solid tumors is 9mg/m 2/dose. Plans for a phase II trial in select pediatric solid tumors are in development.

Original languageEnglish
Pages (from-to)1323-1328
Number of pages6
JournalPediatric Blood and Cancer
Volume55
Issue number7
DOIs
Publication statusPublished - Dec 2010
Externally publishedYes

Keywords

  • Children Oncology Group
  • Ispinesib
  • Pediatric cancer
  • Phase I trials
  • Solid tumors

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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