Intensive cisplatin and cyclophosphamide-based chemotherapy without radiotherapy for intracranial germinomas: Failure of a primary chemotherapy approach Journal Article


Authors: Kellie, S. J.; Boyce, H.; Dunkel, I. J.; Diez, B.; Rosenblum, M.; Brualdi, L.; Finlay, J. L.
Article Title: Intensive cisplatin and cyclophosphamide-based chemotherapy without radiotherapy for intracranial germinomas: Failure of a primary chemotherapy approach
Abstract: Purpose. High rates of overall and event-free survival have been reported in patients with intracranial germinomas-treated with craniospinal radiotherapy. More recently, similar results have been reported with chemotherapy combined with radiotherapy to more localized treatment volumes. Our interest in exploring chemotherapy without radiotherapy in patients with CNS germinomas was based on concerns about the late sequelae of radiotherapy to the brain or neuraxis and also the well documented success of chemotherapy alone in patients with disseminated extracranial germinomas. The primary objective of this study was to determine whether intensive cisplatin and cyclophosphamide-based combination chemotherapy, without radiotherapy, was effective in patients with CNS germinomas. Patients and Methods. Nineteen Patients were enrolled, ranging in age from 1 to 24 years (median, 14 years). Thirteen were male. Nine had diabetes insipidus. Therapy comprised two courses of Regimen 'A' (cisplatin, etoposide, cyclophosphamide, and bleomycin) followed by MRI evaluation. Patients achieving a complete remission (CR) completed all planned therapy with two courses of regimen 'B' (carboplatin, than a CR received two courses of Regimen 'B' followed by another evaluation. Those in CR after four courses of treatment received one additional course of Regimen 'A' and Regimen 'B', while those not in CR after four treatment courses underwent second look surgery and/or radiation therapy. Results. Eleven of 11 patients with residual postoperative disease assessable for response achieved a CR. With a median follow-up of 6.5 years, eight out of 19 (0.42) patients remain in CR 1 without radiotherapy and another three patients are in stable second or subsequent remissions. Three patients died from treatment-related toxicity and another died in CR 1 from an uncharacterized leukoencephalopathy. The 5-year event-tree survival (FFS) was 0.47 +/- 0.23 and 5-year overall survival (OS) was 0.68 +/- 0.22. Conclusions. intensive cisplatin and cyclophosphamide-based chemotherapy was effective in achieving remissions, however, the long-term outcome using this treatment program was unsatisfactory and associated with unacceptable morbidity and mortality, particularly in patients with diabetes insipidus. (C) 2004 Wiley-Liss, Inc.
Keywords: chemotherapy; brain tumor; cranial irradiation; survivors; children; germ cell tumors; radiation-therapy; brain-tumors; randomized-trial; oncology-group; childhood-cancer; germ-cell tumors; sequelae; cns germinomas
Journal Title: Pediatric Blood and Cancer
Volume: 43
Issue: 2
ISSN: 1545-5009
Publisher: Wiley Periodicals, Inc  
Date Published: 2004-08-01
Start Page: 126
End Page: 133
Language: English
ACCESSION: WOS:000222479000008
DOI: 10.1002/pbc.20026
PROVIDER: wos
PUBMED: 15236278
Notes: Article -- Source: Wos
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  1. Ira J Dunkel
    371 Dunkel
  2. Marc Rosenblum
    424 Rosenblum
  3. Jonathan Finlay
    67 Finlay