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Solid Cancers

Phase I study of temozolomide in combination with thiotepa and carboplatin with autologous hematopoietic cell rescue in patients with malignant brain tumors with minimal residual disease

Bone Marrow Transplantation volume 51, pages 542–545 (2016)Cite this article

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Abstract

Recurrence of malignant brain tumors results in a poor prognosis with limited treatment options. High-dose chemotherapy with autologous hematopoietic cell rescue (AHCR) has been used in patients with recurrent malignant brain tumors and has shown improved outcomes compared with standard chemotherapy. Temozolomide is standard therapy for glioblastoma and has also shown activity in patients with medulloblastoma/primitive neuro-ectodermal tumor (PNET), particularly those with recurrent disease. Temozolomide was administered twice daily on days −10 to −6, followed by thiotepa 300 mg/m2 per day and carboplatin dosed using the Calvert formula or body surface area on days −5 to −3, with AHCR day 0. Twenty-seven patients aged 3–46 years were enrolled. Diagnoses included high-grade glioma (n=12); medulloblastoma/PNET (n=9); central nervous system (CNS) germ cell tumor (n=4); ependymoma (n=1) and spinal cord PNET (n=1). Temozolomide doses ranged from 100 mg/m2 per day to 400 mg/m2 per day. There were no toxic deaths. Prolonged survival was noted in several patients including those with recurrent high-grade glioma, medulloblastoma and CNS germ cell tumor. Increased doses of temozolomide are feasible with AHCR. A phase II study using temozolomide, carboplatin and thiotepa with AHCR for children with recurrent malignant brain tumors is being conducted through the Pediatric Blood and Marrow Transplant Consortium.

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Acknowledgements

This study was supported in part by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dolune Corp.

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Authors and Affiliations

  1. Department of Pediatric Oncology, Stephen D Hassenfeld Children’s Center, NYU Langone Medical Center, NYU Cancer Institute, New York, NY, USA

    G Egan, K A Cervone & S L Gardner

  2. Pediatric Neuro-Oncology Program, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    P C Philips & J B Belasco

  3. Division of Hematology/Oncology/BMT, Nationwide Children’s Hospital, Columbus, OH, USA

    J L Finlay

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  1. G Egan
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  6. S L Gardner
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Correspondence to S L Gardner.

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Egan, G., Cervone, K., Philips, P. et al. Phase I study of temozolomide in combination with thiotepa and carboplatin with autologous hematopoietic cell rescue in patients with malignant brain tumors with minimal residual disease. Bone Marrow Transplant 51, 542–545 (2016). https://doi.org/10.1038/bmt.2015.313

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