Division of Genitourinary Malignancies, Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Los Angeles, CA, USA.
Clin Interv Aging. 2010 Dec 3;5:395-402. doi: 10.2147/CIA.S14570.
Docetaxel remains a cornerstone of therapy for the patient with metastatic castration-resistant prostate cancer (CRPC). However, the landscape of CRPC therapy is changing rapidly - recently, data from the phase III TROPIC study revealed a survival advantage with the novel taxane cabazitaxel/prednisone (compared with mitoxantrone/prednisone) in a cohort of 755 men with docetaxel-refractory metastatic CRPC. Interestingly, cabazitaxel bears substantial structural similiarity to docetaxel but appears to be mechanistically distinct. In preclinical studies, the agent has antitumor activity in a variety of docetaxel-refractory in vitro and in vivo models. Subsequent to phase I testing in advanced solid tumors (where neutropenia was identified as a dose-limiting toxicity), the agent was assessed in a phase II trial in advanced, taxane-refractory breast cancer and in the aforementioned phase III TROPIC study. This review describes in detail the preclinical and clinical development of cabazitaxel.
多西他赛仍然是转移性去势抵抗性前列腺癌（CRPC）患者治疗的基石。然而，CRPC 治疗领域正在迅速变化——最近，来自 III 期 TROPIC 研究的数据显示，在 755 名接受多西他赛难治性转移性 CRPC 治疗的男性中，新型紫杉烷卡巴他赛/泼尼松（与米托蒽醌/泼尼松相比）具有生存优势。有趣的是，卡巴他赛与多西他赛具有显著的结构相似性，但在机制上似乎有所不同。在临床前研究中，该药物在多种多西他赛难治性体外和体内模型中具有抗肿瘤活性。在晚期实体瘤的 I 期试验（中性粒细胞减少症被确定为剂量限制性毒性）之后，该药物在晚期、紫杉烷难治性乳腺癌的 II 期试验和上述 III 期 TROPIC 研究中进行了评估。本综述详细描述了卡巴他赛的临床前和临床开发。
