乳腺癌脑转移患者中紫杉醇的 II 期临床试验。
Phase II trial of patupilone in patients with brain metastases from breast cancer.
机构信息
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University (D.M.P., M.S.A.); The Rose Ella Burkhardt Brain Tumor and NeuroOncology Center, Neurological Institute, Cleveland Clinic (D.M.P., M.S.A.); Taussig Cancer Institute, Cleveland Clinic (D.M.P., M.S.A., P.E.); Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio(P.E.); Memorial Sloan-Kettering Cancer Center, New York, New York(C.M., A.C., A.D.S.); Massachusetts General Hospital, Boston, Massachusetts(A.E.); Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan(C.V.P.); Seidman Cancer Center of University Hospitals, Case Medical Center, Cleveland, Ohio(J.B.).
出版信息
Neuro Oncol. 2014 Apr;16(4):579-83. doi: 10.1093/neuonc/not305. Epub 2014 Jan 26.
BACKGROUND
For patients with progressive breast cancer brain metastasis (BCBM) after whole brain radiotherapy (WBRT), few options exist. Patupilone is an epothilone that crosses the blood-brain barrier. We hypothesized that patupilone would produce a 35% 3-month CNS progression-free survival in women with BCBM after WBRT.
METHODS
This multicenter phase II trial included 2 cohorts. Group A included women with progressive BCBM after WBRT. Group B was an exploratory cohort of patients with either leptomeningeal metastases or untreated brain metastases. The primary goal was to observe a 35% 3-month CNS progression-free survival in Group A. The sample size was 45 for Group A and 10 for Group B. Patients received patupilone 10 mg/m(2) once every 3 weeks until progression. Responses were scored according to the Macdonald criteria.
RESULTS
Fifty-five patients (45 in Group A, 10 in Group B) enrolled. In Group A, the 3-month CNS progression-free survival was 27%, the median overall survival was 12.7 months, and the overall response rate was 9%. In Group B, which enrolled 5 patients with leptomeningeal disease and 5 with no prior WBRT, no responses occurred and 8 patients had CNS progression before 3 months. Systemic responses occurred in 15% of patients, including a complete response in liver metastases. Diarrhea occurred in 87% of patients; 25% had grade 3 and 4 adverse events.
CONCLUSIONS
Patupilone in patients with BCBM did not meet the efficacy criteria and had significant gastrointestinal toxicity. Further study of brain-penetrant agents is warranted for patients with CNS metastases from breast cancer.
背景
对于接受全脑放疗（WBRT）后发生进展性乳腺癌脑转移（BCBM）的患者，治疗选择有限。帕他泊隆是一种能够穿过血脑屏障的埃坡霉素。我们假设帕他泊隆可使 WBRT 后发生 BCBM 的女性达到 3 个月时中枢神经系统（CNS）无进展生存率为 35%。
方法
该多中心 2 期临床试验包括 2 个队列。A 组纳入 WBRT 后发生进展性 BCBM 的女性。B 组为探索性队列，包括软脑膜转移或未经治疗的脑转移患者。主要目标是观察 A 组中 3 个月时 CNS 无进展生存率达到 35%。A 组的样本量为 45 例，B 组为 10 例。患者接受帕他泊隆 10mg/m²，每 3 周 1 次，直至进展。根据 MacDonald 标准评价缓解情况。
结果
共 55 例患者（A 组 45 例，B 组 10 例）入组。A 组中，3 个月时 CNS 无进展生存率为 27%，中位总生存时间为 12.7 个月，总缓解率为 9%。B 组中，5 例患者患有软脑膜疾病，5 例患者未接受过 WBRT，无缓解发生，8 例患者在 3 个月内出现 CNS 进展。15%的患者出现了全身缓解，包括肝转移的完全缓解。87%的患者出现腹泻，25%的患者出现 3 级和 4 级不良事件。
结论
帕他泊隆在 BCBM 患者中未达到疗效标准，且具有显著的胃肠道毒性。对于乳腺癌脑转移的患者，需要进一步研究能够穿透血脑屏障的药物。
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