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 language | English |
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Pages (from-to) | 1323-1328 |
Number of pages | 6 |
Journal | Pediatric Blood and Cancer |
Volume | 55 |
Issue number | 7 |
DOIs | |
Publication status | Published - Dec 2010 |
Externally published | Yes |
Keywords
- Children Oncology Group
- Ispinesib
- Pediatric cancer
- Phase I trials
- Solid tumors
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Hematology
- Oncology