Phase I study of temozolomide in paediatric patients with advanced cancer

摘要: A phase I study of temozolomide administered orally once a day, on 5 consecutive days, between 500 and 1200 mg m(-2) per 28-day cycle was performed. Children were stratified according to prior craniospinal irradiation or nitrosourea therapy. Sixteen 20 patients who had not received therapy evaluable. Myelosuppression dose limiting, with Common Toxicity Criteria (CTC) grade 4 thrombocytopenia occurring in one six receiving 1000 cycle, two four treated at cycle. Therefore, the maximum-tolerated (MTD) The MTD defined for children because poor recruitment. Plasma pharmacokinetic analyses showed be rapidly absorbed eliminated, linear increases peak plasma concentrations systemic exposure increasing dose. Responses (CR PR) seen out five high-grade astrocytomas, patient stable disease. One ten diffuse intrinsic brain stem glioma achieved long-term partial response, further recommended II studies have nitrosoureas is Further evaluation gliomas other astrocytomas warranted.