Pal Sumanta Kumar, Twardowski Przemyslaw, Josephson David Y
Division of Genitourinary Malignancies, Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, United States.
Maturitas. 2009 Oct 20;64(2):61-6. doi: 10.1016/j.maturitas.2009.08.004. Epub 2009 Sep 5.
In castrate-resistant prostate cancer, beyond chemotherapy, existing guidelines suggest only supportive care. However, recent evidence suggests that continued targeting of androgen-dependent pathways may be an efficacious approach. Clinical data is now available for two mechanistically distinct agents (abiraterone and MDV3100) that both ultimately target these pathways. Abiraterone is a potent and irreversible inhibitor of CYP17, a critical enzyme in androgen biosynthesis. Phase II studies indicate substantial declines in PSA amongst castrate-resistant patients treated with abiraterone, both prior to and following cytotoxic chemotherapy. In contrast to abiraterone, MDV3100 is a direct inhibitor of the androgen receptor, binding the receptor irreversibly with substantially higher affinity as compared to bicalutamide. A recent phase I/II trial of MDV3100 in castrate-resistant prostate cancer demonstrated tolerability of the agent with activity at the lowest dose level. On the basis of these compelling data, both abiraterone and MDV3100 will be examined in the phase III setting.
在去势抵抗性前列腺癌中，除了化疗之外，现有指南仅建议采取支持性治疗。然而，最近的证据表明，持续靶向雄激素依赖途径可能是一种有效的方法。目前已有两种机制不同的药物（阿比特龙和MDV3100）的临床数据，这两种药物最终均靶向这些途径。阿比特龙是CYP17的一种强效不可逆抑制剂，CYP17是雄激素生物合成中的一种关键酶。II期研究表明，在接受阿比特龙治疗的去势抵抗性患者中，无论在细胞毒性化疗之前还是之后，前列腺特异性抗原（PSA）均大幅下降。与阿比特龙不同，MDV3100是雄激素受体的直接抑制剂，与比卡鲁胺相比，它以高得多的亲和力不可逆地结合该受体。最近一项MDV3100用于去势抵抗性前列腺癌的I/II期试验证明了该药物的耐受性，且在最低剂量水平即具有活性。基于这些令人信服的数据，阿比特龙和MDV3100都将在III期试验中接受检验。
