title: A phase II evaluation of thiotepa followed by other multiagent chemotherapy regimens in infants and young children with malignant brain tumors.
abstract: BACKGROUND
  Chemotherapy may be used to delay the need for cranial irradiation in infants and young children with malignant central nervous system (CNS) tumors. The polyfunctional alkylator thiotepa (TT) possesses significant in vitro and in vivo activity in many central nervous system tumors. Before the introduction of a multiagent chemotherapy previously shown to be active in such tumors, thiotepa alone was evaluated in an upfront therapeutic window.
  
  
  METHODS
  Twenty young children with CNS tumors (19 newly diagnosed, 1 recurrent) were treated with two cycles of TT before response evaluation. Patients on thiotepa without disease progression went on to receive further chemotherapy consisting of alternating cycles of cyclophosphamide plus vincristine, cisplatin plus etoposide, and further TT. Patients with disease progression received radiation therapy.
  
  
  RESULTS
  Low objective rates of response and poor survival led to early study termination. Of 17 patients evaluable for response, 6 (35%) demonstrated disease progression during initial TT therapy. Only two objective responses were noted, both in patients with medulloblastoma. Among the 19 patients evaluable for survival, the overall and progression free survivals were 45% and 20%, respectively, at 3 years postdiagnosis. Myelosuppression was the dominant treatment-related toxicity.
  
  
  CONCLUSIONS
  Although the numbers of patients were small, thiotepa as used in this study was associated with a poor objective response rate and an unacceptably high rate of disease progression. These results may be partly related to TT's significant myelosuppressive effects and the postponement of more effective chemotherapy.
authors.affiliation: Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.
authors.forename: B I
authors.initials: BI
authors.lastname: Razzouk
authors.forename: R L
authors.initials: RL
authors.lastname: Heideman
authors.forename: H S
authors.initials: HS
authors.lastname: Friedman
authors.forename: J J
authors.initials: JJ
authors.lastname: Jenkins
authors.forename: L E
authors.initials: LE
authors.lastname: Kun
authors.forename: D L
authors.initials: DL
authors.lastname: Fairclough
authors.forename: M E
authors.initials: ME
authors.lastname: Horowitz
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010865:Pilot Projects; D013852:Thiotepa / Q000627:therapeutic use*; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D013852:Thiotepa; D002945:Cisplatin