Salvage therapy with single agent bendamustine for recurrent glioblastoma
ABSTRACT The treatment of recurrent glioblastoma (GBM) remains challenging notwithstanding the recent approval of bevacizumab for this indication. Bendamustine has a bifunctional mechanism of action including alkylation, penetrates the CNS and does not show cross resistance to other alkylator chemotherapies. In a single institution phase 2 trial, patients with recurrent GBM were treated with bendamustine (100 mg/m(2)/day administered intravenously for two consecutive days every 4 weeks). The primary study endpoint was 6-month progression free survival (PFS-6). An interim analysis for futility was conducted according to a Simon two-stage minimax design. Complete blood counts were obtained bimonthly, clinical evaluations and brain imaging every month for the first cycle and bimonthly thereafter. Treatment responses were based upon MacDonald criteria. Sixteen patients were enrolled (nine men; seven women), with a median age of 53 years (range 36-68) and a median Karnofsky performance status of 90 (range 70-100). Nine patients were treated at first relapse and seven at second relapse (five patients were bevacizumab failures). A total of 25 cycles of bendamustine were administered with a median of 1 (range 1-6). Bendamustine-related toxicity was seen in eight patients; lymphopenia in seven (5 grade 3; 2 Grade 4), thrombocytopenia in two (1 Grade 3; 1 Grade 4), and neutropenia in one (1 Grade 3). Fourteen patients have died due to disease progression, two patients are alive and on alternative therapies. Only one patient was progression-free at 6 months, triggering the stopping rule for futility. Bendamustine was reasonably well tolerated but failed to meet the study criteria for activity in adults with recurrent GBM.
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ABSTRACT: What is the impact of cytotoxic chemotherapy on disease control and survival in the adult patient with progressive glioblastoma? This recommendation applies to adults patients with progressive glioblastoma. Temozolomide is recommended as superior to procarbazine in patients with first relapse of glioblastoma after having received nitrosourea chemotherapy or no prior cytotoxic chemotherapy at the time of initial therapy. The use of BCNU-impregnated biodegradable polymer wafers is recommended in the management of progressive glioblastoma as a surgical adjunct when cytoreductive surgery is indicated, taking into account the associated toxicities seen with this modality. Consideration of a variety of cytotoxic chemotherapy agents of uncertain benefit is recommended in the setting of progressive glioblastoma based on the judgment of the treating physician taking into account the individual patients prior treatment exposure, systemic health, and likelihood of tolerance of the toxicities of any given agent. It is recommended in such cases that enrollment in available clinical trials be encouraged.Journal of Neuro-Oncology 04/2014; DOI:10.1007/s11060-013-1338-5 · 2.79 Impact Factor
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ABSTRACT: There is comparatively limited therapy for recurrent primary central nervous system lymphoma (PCNSL). Salvage therapies include re-challenge with high-dose methotrexate (HD-MTX), whole brain radiotherapy, temozolomide, topotecan and premetrexed. Bendamustine is a novel bifunctional alkylator with established activity in B cell systemic lymphomas but never previously evaluated in PCNSL. The objective of the current study was to assess response and toxicity of bendamustine in recurrent PCNSL following prior salvage therapy in a retrospective case series. Twelve adults [six males; six females: median age 59 years (range 43-74)] with HD-MTX refractory recurrent PCNSL were treated with bendamustine. All patients were treated at second recurrence following failure of prior salvage therapy. A cycle of bendamustine was defined as two consecutive days of treatment (100 mg/m(2)/day) administered once every 4 weeks (maximum number of cycles 6). Toxicities seen were Grade 2 (24 episodes in 10 patients) and 3 (10 episodes in 5 patients) only and included lymphopenia (8 patients), hyperglycemia (7 patients), fatigue (7 patients) and nausea (4 patients). The median number of cycles of therapy was 3.5 (range 1-6). Radiographic response was progressive disease in 5 (42 %), stable disease in 1 (8 %), partial response in 3 (25 %) and complete response in 3 (25 %). Median progression free survival (PFS) was 3.5 months (range 1-14 months) and 6-month PFS was 33 %. In this small retrospective series of select patients with recurrent PCNSL refractory to HD-MTX, bendamustine appears to have modest single agent activity with manageable toxicity. Confirmation in a larger series of similar patients is required.Journal of Neuro-Oncology 03/2014; 118(1). DOI:10.1007/s11060-014-1411-8 · 2.79 Impact Factor
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ABSTRACT: Central nervous system (CNS) involvement is found in about 1% of multiple myeloma (MM) patients (1). The reported overall survival for these patients usually does not exceed 6 months. Of the different modes of CNS involvement leptomeningeal myeloma is thought to have the worst prognosis (2-4). Here we describe two myeloma patients with leptomeningeal myeloma relapse at 29 and 53 months after diagnosis. Treatment with BTD (bendamustine 70mg/m(2) on day 1, 2, 14 and 15 in a 4-week cycle, thalidomide 100mg daily and dexamethasone 20mg on day 1, 2, 3, 4, 14, 15, 16 and 17) and craniospinal irradiation resulted in disappearance of CNS lesions. The regime did not cause any grade 3 haematological or non-haematological toxicity. Survival from CNS involvement was 14 and 11+ months respectively. This article is protected by copyright. All rights reserved.European Journal Of Haematology 12/2013; 92(5). DOI:10.1111/ejh.12247 · 2.41 Impact Factor