title: Salvage therapy with bendamustine for methotrexate refractory recurrent primary CNS lymphoma: a retrospective case series.
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.
authors.affiliation: Division of Neuro-Oncology, Department of Neurology and Neurological Surgery, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, University of Washington, 825 Eastlake Ave E, MS: G4-940, Seattle, WA, 98109, USA, chambemc@u.washington.edu.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Chamberlain
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D016543:Central Nervous System Neoplasms / Q000188:drug therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009588:Nitrogen Mustard Compounds / Q000627:therapeutic use*; D012189:Retrospective Studies; D016879:Salvage Therapy; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D009588:Nitrogen Mustard Compounds; D000069461:Bendamustine Hydrochloride; D008727:Methotrexate