Phase I Clinical Trial of Mafosfamide in Infants and Children Aged 3 Years or Younger With Newly Diagnosed Embryonal Tumors: A Pediatric Brain Tumor Consortium Study (PBTC-001)

Abstract

Purpose A phase I trial of intrathecal (IT) mafosfamide was performed to determine the optimal dose, dose-limiting toxicities, and incidence and severity of other toxicities when administered in association with concomitant multiagent systemic chemotherapy to children younger than 3 years with newly diagnosed embryonal tumors. Patients and Methods Twenty-five assessable patients received IT mafosfamide at one of six dose levels ranging from 5 mg to 17 mg. Patients were premedicated with dexamethasone (0.15 mg/kg) and morphine (0.1 mg/kg) before receiving IT mafosfamide. Serial samples of CSF for pharmacokinetic studies were obtained in a subset of patients with Ommaya reservoirs. Results Irritability, presumably secondary to pain or headache during mafosfamide administration, was dose limiting in two of three patients at the 17-mg dose level. The maximum-tolerated dose of IT mafosfamide following premedication with dexamethasone and morphine was 14 mg. Conclusion The maximum tolerated dose and recommended phase II dose of IT mafosfamide in patients younger than 3 years with newly diagnosed embryonal CNS tumors is 14 mg. A trial to assess the efficacy of regional therapy with IT mafosfamide administered with intensive systemic chemotherapy in children younger than 3 years with primary intracranial embryonal tumors is now in progress.