Phase I and Pharmacokinetic Studies of Erlotinib Administered Concurrently with Radiotherapy for Children, Adolescents, and Young Adults with High-Grade Glioma

摘要: Purpose: To estimate the maximum-tolerated dose (MTD) of erlotinib administered during and after radiotherapy, to describe pharmacokinetics its metabolite OSI-420 in patients between 3 25 years with newly diagnosed high-grade glioma who did not require enzyme-inducing anticonvulsants. Experimental Design: Five dosage levels (70, 90, 120, 160, 200 mg/m 2 per day) were planned this phase I study. Dose-limiting toxicities (DLT) evaluated first 8 weeks therapy. Local radiotherapy (dose 54 59.4 Gy) started preferentially on same day. Erlotinib was once daily for a maximum years. Pharmacokinetic studies obtained day Mutational analysis EGFR kinase domain, PIK3CA , PTEN done tumor tissue. Results: Median age at diagnosis 23 10.7 (range, 3.7-22.5 years). MTD 120 Skin rash diarrhea generally well controlled supportive care. ( n = 1), increase serum lipase pruritus 1). The pharmacokinetic variables children similar those described adults. However, there no relationship drug exposure. No domain mutations observed. Two glioblastoma harbored 1) or Conclusions: Although day, showed wide interpatient variability