Cancer Chemotherapy and Pharmacology

, Volume 69, Issue 4, pp 1021–1027

Tolerability and pharmacokinetic profile of a sunitinib powder formulation in pediatric patients with refractory solid tumors: a Children’s Oncology Group study

  • Steven G. DuBois
  • Suzanne Shusterman
  • Joel M. Reid
  • Ashish M. Ingle
  • Charlotte H. Ahern
  • Sylvain Baruchel
  • Julia Glade-Bender
  • Percy Ivy
  • Peter C. Adamson
  • Susan M. Blaney
Original Article

DOI: 10.1007/s00280-011-1798-2

Cite this article as:
DuBois, S.G., Shusterman, S., Reid, J.M. et al. Cancer Chemother Pharmacol (2012) 69: 1021. doi:10.1007/s00280-011-1798-2

Abstract

Purpose

Sunitinib is an oral tyrosine kinase inhibitor of VEGF, PDGF, c-KIT, and flt-3 receptors. A pediatric phase I study of sunitinib capsules identified the maximum tolerated dose as 15 mg/m2/day. This study was conducted to evaluate sunitinib given as a powder formulation.

Methods

Sunitinib 15 mg/m2 was administered orally daily for 4 weeks on/2 weeks off to patients <21 years old with refractory solid tumors. Sunitinib capsules were opened, and the powder sprinkled onto applesauce or yogurt. Plasma levels of sunitinib and an active metabolite, SU12662, were measured, and pharmacokinetic parameters were estimated.

Results

12 patients, median age 13 (range 4–21) years, were treated. The most common first-cycle toxicities were leucopenia (n = 6), fatigue (n = 5), neutropenia (n = 4), and hypertension (n = 4). Three patients had dose-limiting toxicities (DLTs) in cycle 1 (dizziness/back pain, hand–foot syndrome, and intratumoral hemorrhage/hypoxia). A median peak plasma sunitinib concentration of 21 (range 6–36) ng/ml was reached at a median of 4 (range 4–8) h after the first dose. The median exposure (AUC0–48) was 585 (range 196–1,059) h ng/l. The median half-life was 23 (range 13–36) h. The median trough concentration measured before day 14 dosing was 32 (range 12–58) ng/ml.

Conclusions

The pharmacokinetic profile of sunitinib appears similar between a powder formulation and published data using capsules. The powder formulation allows patients unable to swallow capsules to receive sunitinib.

Keywords

SunitinibPediatricPharmacokineticsFormulation

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Steven G. DuBois
    • 1
  • Suzanne Shusterman
    • 2
  • Joel M. Reid
    • 3
  • Ashish M. Ingle
    • 4
  • Charlotte H. Ahern
    • 5
  • Sylvain Baruchel
    • 6
  • Julia Glade-Bender
    • 7
  • Percy Ivy
    • 8
  • Peter C. Adamson
    • 9
  • Susan M. Blaney
    • 10
  1. 1.Department of PediatricsUCSF School of MedicineSan FranciscoUSA
  2. 2.Department of Pediatrics, Dana-Farber Cancer Institute, Children’s Hospital BostonHarvard Medical SchoolBostonUSA
  3. 3.Department of PharmacologyMayo College of MedicineRochesterUSA
  4. 4.Children’s Oncology Group Operations CenterArcadiaUSA
  5. 5.Division of Biostatistics, Dan L. Duncan Cancer CenterBaylor College of MedicineHoustonUSA
  6. 6.Department of Hematology/OncologyHospital for Sick ChildrenTorontoCanada
  7. 7.Department of Pediatrics, Morgan Stanley Children’s HospitalColumbia University School of MedicineNew YorkUSA
  8. 8.Cancer Therapy Evaluation ProgramNational Cancer InstituteBethesdaUSA
  9. 9.Department of Oncology, Children’s Hospital of PhiladelphiaUniversity of PennsylvaniaPhiladelphiaUSA
  10. 10.Department of Pediatrics, Texas Children’s Cancer CenterBaylor College of MedicineHoustonUSA