Pachman Deirdre R, Dockter Travis, Zekan Patricia J, Fruth Briant, Ruddy Kathryn J, Ta Lauren E, Lafky Jacqueline M, Dentchev Todor, Le-Lindqwister Nguyet Anh, Sikov William M, Staff Nathan, Beutler Andreas S, Loprinzi Charles L
Department of Oncology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA.
Department of Statistics, Mayo Clinic, Rochester, MN, USA.
Support Care Cancer. 2017 Nov;25(11):3407-3416. doi: 10.1007/s00520-017-3760-2. Epub 2017 May 27.
Paclitaxel is associated with both an acute pain syndrome (P-APS) and chronic chemotherapy-induced peripheral neuropathy (CIPN). Given that extensive animal data suggest that minocycline may prevent chemotherapy-induced neurotoxicity, the purpose of this pilot study was to investigate the efficacy of minocycline for the prevention of CIPN and the P-APS.
Patients with breast cancer were enrolled prior to initiating neoadjuvant or adjuvant weekly paclitaxel for 12 weeks and were randomized to receive minocycline 200 mg on day 1 followed by 100 mg twice daily or a matching placebo. Patients completed (1) an acute pain syndrome questionnaire daily during chemotherapy to measure P-APS and (2) the EORTC QLQ-CIPN20 questionnaire at baseline, prior to each dose of paclitaxel, and monthly for 6 months post treatment, to measure CIPN.
Forty-seven patients were randomized. There were no remarkable differences noted between the minocycline and placebo groups for the overall sensory neuropathy score of the EORTC QLQ-CIPN20 or its individual components, which evaluate tingling, numbness and shooting/burning pain in hands and feet. However, patients taking minocycline had a significant reduction in the daily average pain score attributed to P-APS (p = 0.02). Not only were no increased toxicities reported with minocycline, but there was a significant reduction in fatigue (p = 0.02).
Results of this pilot study do not support the use of minocycline to prevent CIPN, but suggest that it may reduce P-APS and decrease fatigue; further study of the impact of this agent on those endpoints may be warranted.
紫杉醇与急性疼痛综合征（P-APS）和慢性化疗引起的周围神经病变（CIPN）均有关联。鉴于大量动物数据表明米诺环素可能预防化疗引起的神经毒性，本初步研究的目的是调查米诺环素预防CIPN和P-APS的疗效。
乳腺癌患者在开始新辅助或辅助性每周紫杉醇治疗12周之前入组，并随机分为两组，一组在第1天接受200mg米诺环素，随后每日两次，每次100mg；另一组接受匹配的安慰剂。患者完成以下两项任务：（1）化疗期间每天填写急性疼痛综合征问卷，以测量P-APS；（2）在基线时、每次紫杉醇给药前以及治疗后6个月每月填写欧洲癌症研究与治疗组织（EORTC）QLQ-CIPN20问卷，以测量CIPN。
47名患者被随机分组。在EORTC QLQ-CIPN20的总体感觉神经病变评分或其评估手脚刺痛、麻木及刺痛/灼痛的各个组成部分方面，米诺环素组与安慰剂组之间未发现显著差异。然而，服用米诺环素的患者因P-APS导致的每日平均疼痛评分显著降低（p = 0.02）。不仅未报告米诺环素会增加毒性，而且疲劳感显著减轻（p = 0.02）。
本初步研究结果不支持使用米诺环素预防CIPN，但表明其可能减轻P-APS并减轻疲劳；可能有必要进一步研究该药物对这些终点的影响。
