A phase II evaluation of thiotepa followed by other multiagent chemotherapy regimens in infants and young children with malignant brain tumors

Bassem I. Razzouk, Richard L. Heideman, Henry S. Friedman, Jesse J. Jenkins, Larry E. Kun, Diane L. Fairclough, Marc E. Horowitz

Research output: Contribution to journalArticle

21 Scopus citations

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. Cancer 1995;75:2762–7.

Original languageEnglish (US)
Pages (from-to)2762-2767
Number of pages6
JournalCancer
Volume75
Issue number11
DOIs
StatePublished - Jun 1 1995

Keywords

  • brain tumors
  • clinical trial
  • infants
  • medulloblastoma
  • thiotepa

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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