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洛莫司汀用于替莫唑胺难治性复发性间变性星形细胞瘤的挽救治疗:一项回顾性研究

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

作者信息

Chamberlain Marc C

机构信息

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,

出版信息

J Neurooncol. 2015 Apr;122(2):329-38. doi: 10.1007/s11060-014-1714-9. Epub 2015 Jan 7.

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.

摘要

对于复发性间变性星形细胞瘤(AA),目前尚无标准治疗方法。在一项回顾性病例系列研究中,评估洛莫司汀(CCNU)在先前行手术、放疗和替莫唑胺(TMZ)治疗后的复发性AA中的疗效和毒性。35例(18例男性;17例女性:中位年龄42.5岁)TMZ难治性复发性AA患者接受了洛莫司汀治疗。7例患者在首次复发时接受治疗,28例患者在第二次复发时接受治疗。先前的挽救治疗包括再次手术19例、TMZ治疗20例和放疗治疗例。一个洛莫司汀疗程定义为仅在第1天给予110mg/m²,每6 - 8周给药一次。治疗成功定义为6个月时无进展生存率达到40%或更高。3级或4级毒性反应包括贫血(14例患者)、便秘(1例)、疲劳(4例)、淋巴细胞减少(5例)、恶心/呕吐(2例)、中性粒细胞减少(8例)和血小板减少(10例)。未观察到5级毒性反应。治疗周期的中位数为3个(范围1 - 6个)。最佳影像学反应为疾病进展14例(40%)、疾病稳定19例(54%)和部分缓解2例(5.7%)。中位无进展生存期(PFS)为4.5个月(范围1.5 - 12个月),6个月PFS为40%,12个月PFS为11.4%。CCNU开始治疗后的中位生存期为9.5个月(范围2.5 - 15个月)。中位总生存期为2.7年(范围1.7 - 4.3年)。在这个小型回顾性系列研究中,对于TMZ难治的复发性AA患者,洛莫司汀似乎是一种毒性可管理的适度单药治疗药物。需要在更大系列的类似患者中进行验证。

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