Parshad Shruti, Sidhu Amanjot K, Khan Nabeeha, Naoum Andrew, Emmenegger Urban
Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada.
Biological Sciences Research Platform, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada.
J Clin Med. 2022 May 15;11(10):2783. doi: 10.3390/jcm11102783.
Metastatic castration-resistant prostate cancer (mCRPC) is the ultimately lethal form of prostate cancer. Docetaxel chemotherapy was the first life-prolonging treatment for mCRPC; however, the standard maximally tolerated dose (MTD) docetaxel regimen is often not considered for patients with mCRPC who are older and/or frail due to its toxicity. Low-dose metronomic chemotherapy (LDMC) is the frequent administration of typically oral and off-patent chemotherapeutics at low doses, which is associated with a superior safety profile and higher tolerability than MTD chemotherapy. We conducted a systematic literature review using the PUBMED, EMBASE, and MEDLINE electronic databases to identify clinical studies that examined the impact of LDMC on patients with advanced prostate cancer. The search identified 30 reports that retrospectively or prospectively investigated LDMC, 29 of which focused on mCRPC. Cyclophosphamide was the most commonly used agent integrated into 27/30 (90%) of LDMC regimens. LDMC resulted in a clinical benefit rate of 56.8 ± 24.5% across all studies. Overall, there were only a few non-hematological grade 3 or 4 adverse events reported. As such, LDMC is a well-tolerated treatment option for patients with mCRPC, including those who are older and frail. Furthermore, LDMC is considered more affordable than conventional mCRPC therapies. However, prospective phase III trials are needed to further characterize the efficacy and safety of LDMC in mCRPC before its use in practice.
转移性去势抵抗性前列腺癌（mCRPC）是前列腺癌的最终致命形式。多西他赛化疗是首个用于延长mCRPC患者生命的治疗方法；然而，由于其毒性，对于年龄较大和/或身体虚弱的mCRPC患者，通常不考虑使用标准的最大耐受剂量（MTD）多西他赛方案。低剂量节拍化疗（LDMC）是指频繁给予通常为口服且已过专利保护期的低剂量化疗药物，与MTD化疗相比，其安全性更高，耐受性更好。我们使用PUBMED、EMBASE和MEDLINE电子数据库进行了一项系统的文献综述，以确定研究LDMC对晚期前列腺癌患者影响的临床研究。检索发现30篇回顾性或前瞻性研究LDMC的报告，其中29篇聚焦于mCRPC。环磷酰胺是最常用的药物，纳入了30个LDMC方案中的27个（90%）。在所有研究中，LDMC的临床获益率为56.8±24.5%。总体而言，仅报告了少数非血液学3级或4级不良事件。因此，LDMC对于mCRPC患者是一种耐受性良好的治疗选择，包括年龄较大和身体虚弱的患者。此外，LDMC被认为比传统的mCRPC治疗更经济实惠。然而，在实际应用之前，需要进行前瞻性III期试验以进一步明确LDMC在mCRPC中的疗效和安全性。
