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Salvage therapy with bendamustine for temozolomide refractory recurrent anaplastic gliomas: a prospective phase II trial

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Abstract

There is no standard therapy for recurrent anaplastic glioma (AG). Salvage therapies include alkylator-based chemotherapy, re-resection with or without carmustine implants, re-irradiation and bevacizumab. Bendamustine is a novel bifunctional alkylator with CNS penetration never previously evaluated in AG. Assess response and toxicity of bendamustine in recurrent AG in a phase II trial. Adults with radiation and temozolomide refractory recurrent AG were treated with bendamustine. A cycle of bendamustine was defined as two consecutive days of treatment (100 mg/m2/day) administered once every 4 weeks. Success of treatment was defined as progression free survival (PFS) at 6 months of 40 % or better. Twenty-six adults [16 males; 10 females: median age 40 years (range 30–65)] were treated, 12 at first recurrence and 17 at second recurrence. Prior salvage therapy included re-resection (14), chemotherapy (11) and re-radiation (2). Grade 3 treatment-related toxicities included lymphopenia (11 patients; Grade 4 in 3), myalgia, pneumonia, diarrhea, leukopenia, allergic reaction and thrombocytopenia in one patient each. One patient discontinued therapy due to toxicity. There were five instances of bendamustine dose delays all due to lymphopenia. There were no dose reductions due to toxicity. The median number of cycles of therapy was 3 (range 1–8). Best radiographic response was progressive disease in 12 (46 %), stable disease in 13 (50 %) and partial response in 1 (4 %). Median, 6- and 12-month PFS was 2.7 months (range 1–52), 27 and 8 % respectively. In patients with recurrent AG refractory to Z, bendamustine has manageable toxicity and modest single agent activity though not meeting pre-specified study criteria.

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Acknowledgments

The authors want to thank Sandra Johnston and Alisa Clein for their organizational and administrative assistance in developing the study and manuscript.

Disclosure

MC Chamberlain and Bryan Kim collected and analyzed data. No personal communications cited in the manuscript.

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Authors and Affiliations

  1. Division of Neuro-Oncology, Department of Neurology and Neurological Surgery, Fred Hutchinson Cancer Research Center, University of Washington, Seattle Cancer Care Alliance, 825 Eastlake Ave E, MS: G4-940, Seattle, WA, 98109, USA

    Marc C. Chamberlain

  2. Department of Neurosurgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Howard Colman

  3. Department of Neurology, University of Washington, Seattle, WA, USA

    Bryan T. Kim

  4. Department of Neurology, Northwestern University, Chicago, IL, USA

    Jeffrey Raizer

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  1. Marc C. Chamberlain
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  2. Howard Colman
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  4. Jeffrey Raizer
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Correspondence to Marc C. Chamberlain.

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Chamberlain, M.C., Colman, H., Kim, B.T. et al. Salvage therapy with bendamustine for temozolomide refractory recurrent anaplastic gliomas: a prospective phase II trial. J Neurooncol 131, 507–516 (2017). https://doi.org/10.1007/s11060-016-2241-7

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  • DOI: https://doi.org/10.1007/s11060-016-2241-7

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