title: Salvage therapy with lomustine for temozolomide refractory recurrent anaplastic astrocytoma: a retrospective study.
abstract: There is no standard therapy for recurrent anaplastic astrocytoma (AA). Assess response and toxicity of lomustine (CCNU) in recurrent AA following prior surgery, radiotherapy and TMZ in a retrospective case series. Thirty-five adults (18 males; 17 females: median age 42.5 years) with TMZ refractory recurrent AA were treated with lomustine. Seven patients were treated at 1st recurrence and 28 patients were treated at 2nd recurrence. Prior salvage therapy included re-resection in 19, TMZ in 20 and radiotherapy in 7. A cycle of lomustine was defined as 110 mg/m(2) on day 1 only administered once every 6-8 weeks. Success of treatment was defined as progression free survival at 6 months of 40 % or better. Grade 3 or 4 toxicities included anemia (14 patients), constipation (1), fatigue (4), lymphopenia (5), nausea/vomiting (2), neutropenia (8) and thrombocytopenia (10). No grade five toxicities were seen. The median number of cycles of therapy was 3 (range 1-6). Best radiographic response was progressive disease in 14 (40 %), stable disease in 19 (54 %) and partial response in 2 (5.7 %). Median progression free survival (PFS) was 4.5 months (range 1.5-12 months), 6-month PFS was 40 % and 12 month PFS was 11.4 %. Median survival after onset of CCNU was 9.5 months (range 2.5-15 months). Median overall survival was 2.7 years (range 1.7-4.3). In this small retrospective series of patients with recurrent AA refractory to TMZ, lomustine appears to have modest single agent 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, University of Washington/Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, 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; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use* / Q000633:toxicity; D001254:Astrocytoma / Q000628:therapy*; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000628:therapy*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008130:Lomustine / Q000627:therapeutic use* / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D000077204:Temozolomide; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D008130:Lomustine; D003606:Dacarbazine; D000077204:Temozolomide