Wednesday, December 21, 2011 (Last Updated: 12/22/2011)WEDNESDAY, Dec. 21 (HealthDay News) -- Cixutumumab is well tolerated in children with refractory solid tumors, but limited single-agent activity is seen in Ewing sarcoma (ES), according to a study published online Dec. 19 in the Journal of Clinical Oncology.
Suman Malempati, M.D., from the Oregon Health and Science University in Portland, and colleagues assessed the toxicities, pharmacokinetics, and pharmacodynamics of cixutumumab in children to identify the recommended phase II dose, and to assess antitumor activity in ES. Patients with a median age of 15 years, with relapsed or refractory solid tumors, received cixutumumab as a once-a-week one-hour intravenous infusion. Two dose levels (6 and 9 mg/kg) were assessed, using 12 patients in a standard three-plus-three cohort design. At each dose level, patients with refractory ES were treated in an expanded phase II cohort.
The investigators found that there were mild and infrequent hematologic and nonhematologic toxicities. At 6 mg/kg the dose-limiting toxicity was grade 4 thrombocytopenia, whereas at 9 mg/kg it was grade 3 dehydration. At 9 mg/kg the mean trough concentration was 106 ± 57 µg/mL. Confirmed partial responses were seen in three patients with ES: in one of 10 patients treated with 6 mg/kg and in two of 20 treated at 9 mg/kg. A consistent increase was seen in serum insulin-like growth factor I (IGF-I) levels after one dose of cixutumumab. There was no correlation between tumor IGF-I receptor expression by immunohistochemistry and response in patients with ES.
"Cixutumumab is well tolerated in children with refractory solid tumors. The recommended phase II dose is 9 mg/kg. Limited single-agent activity of cixutumumab was seen in ES," the authors write.
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