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Phase I study of bendamustine with concurrent whole brain radiation therapy in patients with brain metastases from solid tumors

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Abstract

A phase I study was conducted to evaluate the dose-limiting toxicities (DLTs) and to determine the maximum tolerated dose (MTD)/recommended phase II dose of bendamustine with concurrent whole brain radiation (WBR) in patients with brain metastases (BM) from solid tumors. Four doses of intravenous weekly bendamustine were administered with 3 weeks of WBR at three dose levels (60, 80, and 100 mg/m2) according to a standard 3 + 3 phase I design. A total of 12 patients with solid tumor BM were enrolled in the study (six with non-small cell lung cancer, four with melanoma, one with breast cancer, and one with neuroendocrine carcinoma). The first two dose levels had three patients each, and the third dose level had six total patients. Plasma pharmacokinetic studies of bendamustine demonstrated no significant differences from pharmacokinetic characteristics of bendamustine in other studies. No DLTs were noted at any dose levels, and no grade 4 toxicities occurred. The MTD of weekly bendamustine with concurrent WBR was 100 mg/m2. The majority of trial patients died from progressive systemic disease rather than their brain disease. The combination of weekly bendamustine with concurrent WBR was acceptably tolerated. The efficacy of this combination may be evaluated in a phase II trial with stratification by histologies.

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Acknowledgments

This study was approved and funded by the National Comprehensive Cancer Network (NCCN) from general research support provided by Cephalon, Inc. d/b/a Teva Pharmaceuticals. The authors would like to thank Rasa Hamilton (Moffitt Cancer Center) for her work in manuscript editing.

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Authors and Affiliations

  1. Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, 5323 Harry Hines Blvd. ND3.300A, Dallas, TX, 75390-9186, USA

    Edward Pan

  2. Department of Clinical Sciences, Temple University School of Medicine, Philadelphia, PA, USA

    Daohai Yu

  3. H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Xiuhua Zhao, Anthony Neuger, Pamela Smith & Prakash Chinnaiyan

  4. Sinai Hospital of Baltimore, Baltimore, MD, USA

    Hsiang-Hsuan Michael Yu

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  1. Edward Pan
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  2. Daohai Yu
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  7. Hsiang-Hsuan Michael Yu
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Correspondence to Edward Pan.

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Pan, E., Yu, D., Zhao, X. et al. Phase I study of bendamustine with concurrent whole brain radiation therapy in patients with brain metastases from solid tumors. J Neurooncol 119, 413–420 (2014). https://doi.org/10.1007/s11060-014-1510-6

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  • DOI: https://doi.org/10.1007/s11060-014-1510-6

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