title: 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: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Texas Children's Cancer Center, 6621 Fannin, CC 1410.00, Houston, TX 77030, USA. sblaney@txccc.org
authors.forename: Susan M
authors.initials: SM
authors.lastname: Blaney
authors.forename: James
authors.initials: J
authors.lastname: Boyett
authors.forename: Henry
authors.initials: H
authors.lastname: Friedman
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
authors.forename: Russ
authors.initials: R
authors.lastname: Geyer
authors.forename: Marc
authors.initials: M
authors.lastname: Horowtiz
authors.forename: Daniel
authors.initials: D
authors.lastname: Hunt
authors.forename: Mark
authors.initials: M
authors.lastname: Kieran
authors.forename: Larry
authors.initials: L
authors.lastname: Kun
authors.forename: Roger
authors.initials: R
authors.lastname: Packer
authors.forename: Peter
authors.initials: P
authors.lastname: Phillips
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
authors.forename: Michael
authors.initials: M
authors.lastname: Prados
authors.forename: Richard
authors.initials: R
authors.lastname: Heideman
mesh_terms: D000339:Affect; D000367:Age Factors; D000701:Analgesics, Opioid / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007223:Infant; D007278:Injections, Spinal; D008297:Male; D020714:Maximum Tolerated Dose; D009020:Morphine / Q000008:administration & dosage; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000473:pathology; D010146:Pain / Q000209:etiology
chemical_list: D000701:Analgesics, Opioid; D000970:Antineoplastic Agents; D005938:Glucocorticoids; C048341:mafosfamide; D009020:Morphine; D003907:Dexamethasone; D003520:Cyclophosphamide