Goenka Luxitaa, Dubashi Biswajit, Selvarajan Sandhiya, Ganesan Prasanth
Departments of Medical Oncology.
Clinical Pharmacology, JIPMER, Puducherry, Puducherry, India.
Am J Clin Oncol. 2022 Apr 1;45(4):168-174. doi: 10.1097/COC.0000000000000900.
Epithelial ovarian cancer has poor outcomes with standard therapy and limited options for treatment of recurrent disease. This systematic review summarizes the data on the clinical use of repurposed drugs. We searched for clinical studies using "repurposed" agents for the treatment of ovarian cancer in the following databases: PubMed, clinicaltrials.gov, Clinical Trial Registry of India, European Clinical Trials Registry, and Chinese Clinical Trial Registry. We excluded reviews, preclinical studies, and non-English language studies. We assessed the quality of included studies. The following agents/class of agents were included: statins, hydroxychloroquine, metformin, itraconazole, nonsteroidal anti-inflammatory drugs, vitamin D, proton pump inhibitors, beta-blockers, and sodium valproate. Only one randomized controlled trial investigated metformin, which found no benefit of metformin. However, this had a high risk of bias (no details of randomization). Among the observational studies, 70% were of high quality (Newcastle-Ottawa scale ≥7). Clinical benefit was seen for itraconazole, beta-blockers, metformin, statins, and proton pump inhibitors. Though multiple studies aim to repurpose agents in epithelial ovarian cancer, the most published literature is observational, and none are practice-changing. Given the solid preclinical data regarding the anticancer efficacy of these agents, well-designed clinical trials are urgently required.
上皮性卵巢癌采用标准治疗的预后较差，复发性疾病的治疗选择有限。本系统评价总结了关于重新利用药物临床应用的数据。我们在以下数据库中检索了使用“重新利用”药物治疗卵巢癌的临床研究：PubMed、clinicaltrials.gov、印度临床试验注册库、欧洲临床试验注册库和中国临床试验注册库。我们排除了综述、临床前研究和非英语语言研究。我们评估了纳入研究的质量。纳入的药物/药物类别如下：他汀类药物、羟氯喹、二甲双胍、伊曲康唑、非甾体抗炎药、维生素D、质子泵抑制剂、β受体阻滞剂和丙戊酸钠。只有一项随机对照试验研究了二甲双胍，该研究未发现二甲双胍有获益。然而，该研究存在较高的偏倚风险（随机化无详细信息）。在观察性研究中，70%质量较高（纽卡斯尔-渥太华量表≥7）。伊曲康唑、β受体阻滞剂、二甲双胍、他汀类药物和质子泵抑制剂显示出临床获益。尽管多项研究旨在重新利用药物治疗上皮性卵巢癌，但发表的文献大多是观察性的，且没有一项能改变临床实践。鉴于这些药物抗癌疗效的可靠临床前数据，迫切需要设计良好的临床试验。
