Phase I and pharmacokinetic study of sunitinib in pediatric patients with refractory solid tumors: A children's oncology group study

Steven G. DuBois, Suzanne Shusterman, Ashish M. Ingle, Charlotte H. Ahern, Joel M. Reid, Bing Wu, Sylvain Baruchel, Julia Glade-Bender, Percy Ivy, Holcombe E. Grier, Peter C. Adamson, Susan M. Blaney

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


Purpose: Sunitinib is an oral multitargeted receptor tyrosine kinase inhibitor. The purpose of this study was to determine the recommended phase 2 dose, pharmacokinetics, pharmacodynamic effects, and preliminary antitumor activity of sunitinib in a pediatric population. Experimental Design: Patients who were 2 to 21 years of age with refractory solid tumors were eligible if they had measurable or evaluable disease and met baseline organ function requirements. Patients received sunitinib once daily for 28 days followed by a 14-day break between each cycle. Dose levels of 15 and 20 mg/m 2/d were evaluated, with dose escalation based on a 3 + 3 design. Sunitinib pharmacokinetics and biomarkers of angiogenesis were also evaluated during the first cycle. Results: Twenty-three patients were treated (median age 13.9 years; range, 3.9-20.6 years). The most common toxicities were neutropenia, thrombocytopenia, elevated liver transaminases, gastrointestinal symptoms, and fatigue. Two patients developed dose-limiting reductions in cardiac ejection fraction prompting a protocol amendment to exclude patients with previous exposure to anthracyclines or cardiac radiation. In patients without these cardiac risk factors, the maximum tolerated dose (MTD) was 15 mg/m 2/d. Steady-state plasma concentrations were reached by day 7. No objective responses were observed. Four patients with sarcoma and glioma had stable disease for 2 to 9 cycles. Conclusions: Cardiac toxicity precluded determination of a recommended dose for pediatric patients with previous anthracycline or cardiac radiation exposure. The MTD of sunitinib for patients without risk factors for cardiac toxicity is 15 mg/m 2/d for 28 days followed by a 14-day break.

Original languageEnglish (US)
Pages (from-to)5113-5122
Number of pages10
JournalClinical Cancer Research
Issue number15
StatePublished - Aug 1 2011

ASJC Scopus subject areas

  • General Medicine


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