Salvage therapy with lomustine for temozolomide refractory recurrent anaplastic astrocytoma: a retrospective study

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/m² 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.