title: Phase I study of temozolomide in children and adolescents with recurrent solid tumors: a report from the Children's Cancer Group.
abstract: OBJECTIVE
  The Children's Cancer Group conducted a phase I trial of temozolomide stratified by prior craniospinal irradiation (CSI).
  
  
  METHODS
  Children and adolescents with recurrent or progressive cancer were enrolled. Temozolomide was administered orally daily for 5 days, with subsequent courses administered every 21 to 28 days after full hematologic recovery. Dose levels tested included 100, 150, 180, 215, 245, and 260 mg/m2 daily.
  
  
  RESULTS
  Twenty-seven patients on the non-CSI stratum were assessable for hematologic toxicity. During the first three dose levels (100, 150, and 180 mg/m2 daily), only grades 1 and 2 hematologic toxicity occurred. One patient at 215 mg/m2 daily had grade 3 hematologic toxicity. Three of eight patients (38%) treated at 245 to 260 mg/m2 daily had dose-limiting toxicity (DLT), which included both neutropenia and thrombocytopenia. Twenty-two patients on the CSI stratum were assessable for hematologic toxicity. Hematologic DLT occurred in one of six patients (17%) at 100 mg/m2 daily and in two of four patients (50%) at 215 mg/m2 daily. No nonhematologic DLT occurred; nausea and vomiting occurred in more than half of the patients. After two courses of temozolomide, 10 patients had stable disease (SD), and three patients had a partial response (PR), one of whom subsequently had a complete response (CR) that persists through 24 months of follow-up.
  
  
  CONCLUSIONS
  The maximum-tolerated dose (MTD) of temozolomide for children and adolescents without prior CSI is 215 mg/m2 daily and for those with prior CSI is 180 mg/m2 daily for 5 days, with subsequent courses that begin on day 28. Temozolomide is well tolerated and should undergo phase II testing in children and adolescents.
authors.affiliation: Department of Hematology-Oncology, Children's National Medical Center, Washington, DC, USA. nicholss@ohsu.edu
authors.forename: H S
authors.initials: HS
authors.lastname: Nicholson
authors.forename: M
authors.initials: M
authors.lastname: Krailo
authors.forename: M M
authors.initials: MM
authors.lastname: Ames
authors.forename: N L
authors.initials: NL
authors.lastname: Seibel
authors.forename: J M
authors.initials: JM
authors.lastname: Reid
authors.forename: W
authors.initials: W
authors.lastname: Liu-Mares
authors.forename: L G
authors.initials: LG
authors.lastname: Vezina
authors.forename: A G
authors.initials: AG
authors.lastname: Ettinger
authors.forename: G H
authors.initials: GH
authors.lastname: Reaman
mesh_terms: D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy*; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide