顺铂分三次化疗新方案用于晚期乳腺癌
顺铂是有效的晚期乳腺癌化疗药物之一，常规推荐每3周第1天给药剂量为75mg/m²。不过，75mg/m²的给药方案通常引起恶心呕吐、肾脏毒性、低镁血症等多种副作用，故需长时间的水化治疗。分3天给药（第1～3天每天25mg/m²）不需水化，是标准方案的替代方法。
2020年6月10日，施普林格自然旗下《乳腺癌研究与治疗》在线发表复旦大学附属肿瘤医院张金凤、林明曦、李婷、王碧芸、王磊苹、张盛、曹君、陶中华、张剑、胡夕春等学者的研究报告，比较了顺铂两种给药方案对晚期乳腺癌患者的疗效和毒性。
该单中心回顾研究对2008年12月～2019年6月复旦大学附属肿瘤医院入组3项顺铂临床研究的晚期乳腺癌患者客观缓解率、无进展生存和毒性反应进行回顾分析：
NCT02546934: A Phase III, Multicenter, Randomized Study of ABX Plus Cisplatin (AP) Versus Gemcitabine Plus Cisplatin (GP) as First-Line Treatment in Patients With Advanced Triple-Negative Breast Cancer (CBCSG018)
NCT01149798: A Single Institutional Phase II Clinical Trial of Abraxane Combined With Cisplatin in Metastatic Breast Cancer
NCT00601159: Phase II Study of Gemcitabine and Cisplatin as First Line Combination Therapy in Patients With Triple-negative MBC
结果，227例患者接受了顺铂1天给药方案、256例患者接受了顺铂3天给药方案：
中位无进展生存：6.68比6.70个月（5.66～7.70、5.89～7.52，风险比：0.942，95%置信区间：0.759～1.170，P=0.589）
完全或部分缓解：44.9%比44.5%（P=0.929）
恶心和呕吐比例：61.2%比51.6%（P=0.033）
低血镁发生比例：43.2%比28.3%（P=0.016）
其他副作用相似
因此，该研究结果表明，对于晚期乳腺癌，顺铂75mg/m²分3天给药与1天给药相比，疗效相似、不需水化治疗、化疗所致恶心呕吐和低镁血症较少，可能成为一个不错的替代方案。
Breast Cancer Res Treat. 2020 Jun 10. Online ahead of print.
Cisplatin given at three divided doses for three consecutive days in metastatic breast cancer: an alternative schedule for one full dose with comparable efficacy but less CINV and hypomagnesaemia.
Jinfeng Zhang, Mingxi Lin, Yizi Jin, Linhan Gu, Ting Li, Baoying Yuan, Biyun Wang, Leiping Wang, Sheng Zhang, Jun Cao, Zhonghua Tao, Jian Zhang, Xichun Hu.
Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Fengxian Central Hospital, Branch of The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China; The Second Clinical Medical School, Anhui Medical University, Anhui, China; Zhongshan Hospital, Fudan University, Shanghai, China.
PURPOSE: Cisplatin, an effective medication for metastatic breast cancer (MBC), is recommended to be applied at the dose of 75 mg/m² on day 1 every 3 weeks. However, the 75 mg/m² schedule is often associated with a variety of side effects (such as vomiting and kidney toxicity), and time-consuming hydration treatment is usually needed. Divided dose (25 mg/m² on day 1-3) without hydration is an alternative. This study aimed to compare the efficacy and toxicity profiles between these two dosage regimens.
METHODS: Patients with MBC treated with cisplatin-based regimens in Fudan University Shanghai Cancer Center between December 2008 and June 2019 were retrospectively analyzed. Objective response rate (ORR), progression-free survival (PFS), and toxicity profiles were analyzed.
RESULTS: 227 patients receiving a 1-day schedule and 256 patients receiving a 3-day schedule were included. Median PFS was 6.68 (5.66-7.70) months for patients in the 1-day schedule group and 6.70 (5.89-7.52) months for patients in the 3-day schedule group. There was no statistically significant difference in PFS between the two treatment groups (hazard ratio, 0.942; 95% CI 0.759 to 1.170; P=0.589). The ORRs were comparable between the two groups. ORRs were 44.9% in 1-day schedule group and 44.5% in 3-day schedule group, respectively (P=0.929). Compared with patients in the 3-day schedule group, patients in the 1-day schedule group experienced higher rates of chemotherapy-induced nausea and vomiting (CINV) (139 [61.2%] vs. 132 [51.6%], P=0.033). The risk of hypomagnesaemia was also significantly higher (43.2% vs. 28.3%, P=0.016) among patients receiving 1-day schedule (without magnesium supplementation). No other differences in adverse events were observed between the two groups.
CONCLUSIONS: Cisplatin given at three divided doses with no hydration in MBC is a less toxic (less CINV and hypomagnesaemia) schedule with comparable efficacy. Thus, it may be a good alternative for one full-dose (75 mg/m²) schedule.
KEYWORDS: Cisplatin, Metastatic breast cancer, Chemotherapy-induced nausea and vomiting, Hypomagnesemia, Nephrotoxicity
DOI: 10.1007/s10549-020-05730-2