title: Temozolomide in resistant or relapsed pediatric solid tumors.
abstract: OBJECTIVE
  We report the off-label study aimed at investigating the use of temozolomide (TMZ) as single agent in relapsed or resistant pediatric solid tumors. The drug was administered at the dose of 215 mg/m2/day x 5 days or 180 mg/m2/day x 5 days in patients with prior craniospinal irradiation (CSI) or autologous bone marrow transplantation (ABMT).
  
  
  METHODS
  Fifty two patients, median age 127.6 months, with resistant or relapsed solid tumors were enrolled. Tumor types were: neuroblastoma (NB; n = 17), medulloblastoma (MB; 8), brain stem glioma (BSG; 8), extraosseous Ewing's sarcoma/peripheral neuroectodermal tumor (EOES; 4), Ewing's sarcoma (ES; 4), anaplastic astrocytoma (AA; 3), rhabdomyosarcoma (RMS; 2), ependymoma (EP; 2), cerebral primitive neuroectodermal tumor (cPNET; 2), hepatocarcinoma (HC; 1), and osteosarcoma (OS; 1). All patients were pre-treated. Two outpatient courses were administered, with a median of 4.8 courses/pt.
  
  
  RESULTS
  Objective response-rate (CR + PR + MR) in our series was 13.4% (1.9% CR, 3.8% PR, and 7.7% MR), SD occurred in 38.4% of patients and 48% had PD. The median survival was 7.8 months (range 1-37) and median time to progression was 3.4 months (range 1-20); these data were significantly correlated with histology and previous nitrosureas administration in multivariate analysis. Haematological toxicity grade 3-4 (mainly thrombocytopenia) was observed in 21.4% of administered courses, nausea was reported in 3.1% and respiratory distress in 0.7%.
  
  
  CONCLUSIONS
  Oral TMZ was well tolerated in children with resistant or relapsed solid tumors and showed activity in NB and CNS tumours refractory to standard chemotherapy.
authors.affiliation: Division and Laboratory of Oncology, Department of Pediatric of Pediatric Oncology Oncology-Haematology and Blood Bank Service, Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: De Sio
authors.forename: G M
authors.initials: GM
authors.lastname: Milano
authors.forename: A
authors.initials: A
authors.lastname: Castellano
authors.forename: A
authors.initials: A
authors.lastname: Jenkner
authors.forename: P
authors.initials: P
authors.lastname: Fidani
authors.forename: C
authors.initials: C
authors.lastname: Dominici
authors.forename: A
authors.initials: A
authors.lastname: Donfrancesco
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; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide