Phase I trial and pharmacokinetic study of bevacizumab in pediatric patients with refractory solid tumors: A Children's Oncology Group study

Julia L. Glade Bender, Peter C. Adamson, Joel M Reid, Lu Xu, Sylvain Baruchel, Yuval Shaked, Robert S. Kerbel, Erin M. Cooney-Qualter, Diana Stempak, Helen X. Chen, Marvin D. Nelson, Mark D. Krailo, Ashish M. Ingle, Susan M. Blaney, Jessica J. Kandel, Darrell J. Yamashiro

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Abstract

Purpose: We conducted a pediatric phase I trial of the vascular endothelial growth factor (VEGF)-neutralizing antibody bevacizumab (BV). Primary aims included estimating the maximum-tolerated dose (MTD) and determining the dose-limiting toxicities (DLTs), pharmacokinetics, and biologic effects of BV in children with cancer. Patients and Methods: BV (5, 10, 15 mg/kg) was administered intravenously every 2 weeks in 28-day courses to children with refractory solid tumors. Results: Twenty-one patients enrolled, 20 (median age, 13 years) were eligible, and 18 completed one course and were fully assessable for toxicity. A total of 67 courses were administered (median, three courses per patient; range, one to 16 courses). Treatment was well tolerated with no DLTs observed. Non-DLTs included infusional reaction, rash, mucositis, proteinuria, and lymphopenia. Increases in systolic and diastolic blood pressure not meeting Common Terminology Criteria for Adverse Events (CTCAEv3) pediatric-specific criteria for hypertension were observed. There was no hemorrhage or thrombosis. Growth perturbation was not detected in a limited sample over the first course. The serum exposure to BV as measured by area under the concentration-time curve (AUC) seemed to increase in proportion to dose. The median clearance of BV was 4.1 mL/d/kg (range, 3.1 to 15.5 mL/d/kg), and the median half-life was 11.8 days (range, 4.4 to 14.6 days). No objective responses were observed. Exploratory analyses on circulating endothelial mobilization and viability are consistent with the available adult data. Conclusion: BV is well tolerated in children. Phase II pediatric studies of BV in combination with chemotherapy in dosing schedules similar to adults are planned.

Original languageEnglish (US)
Pages (from-to)399-405
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number3
DOIs
StatePublished - Jan 20 2008

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Glade Bender, J. L., Adamson, P. C., Reid, J. M., Xu, L., Baruchel, S., Shaked, Y., Kerbel, R. S., Cooney-Qualter, E. M., Stempak, D., Chen, H. X., Nelson, M. D., Krailo, M. D., Ingle, A. M., Blaney, S. M., Kandel, J. J., & Yamashiro, D. J. (2008). Phase I trial and pharmacokinetic study of bevacizumab in pediatric patients with refractory solid tumors: A Children's Oncology Group study. Journal of Clinical Oncology, 26(3), 399-405. https://doi.org/10.1200/JCO.2007.11.9230