Niraula Saroj, Pond Greg, de Wit Ronald, Eisenberger Mario, Tannock Ian F, Joshua Anthony M
Division of Medical Oncology, Princess Margaret Hospital/University of Toronto, Toronto, ON;
Can Urol Assoc J. 2013 Jan-Feb;7(1-2):E74-81. doi: 10.5489/cuaj.267.
The TAX 327 trial was pivotal in establishing docetaxel in castration refractory metastatic prostate cancer. Various commonly prescribed and over-the-counter co-administered medications are thought to exhibit anti-neoplastic properties and/or could potentially have pharmacokinectic interactions with docetaxel lessening the effectiveness of chemotherapy.
To examine the effect of on prostate cancer outcomes within this trial, we examined overall survival, prostate-specific antigen (PSA) response, percent PSA reduction, pain response and QOL responses for 14 families of medications including metformin, digoxin, verapamil, proton pump inhibitors, nitrates, statins, cox-2 inhibitors, warfarin, heparins, ascorbic acid, selenium, tocopherol, antidepressants and erythropoietin.
Our findings did not reveal any medication that had a significant additive or synergistic effect with docetaxel. We did note, however, that patients on digoxin or verapamil had poorer overall survival, possibly due to a trend of fewer cycles of administered chemotherapy being administered to the verapamil group, consistent with a pharmacokinectic interaction.
These data are only hypothesis-generating given the statistical limitations, but may form a basis for similar future analysis in other malignancies. The data suggest the need to be aware of pharmacokinectic interactions with medications that may interact with docetaxel.
TAX 327试验在确立多西他赛用于去势难治性转移性前列腺癌的治疗方面具有关键作用。各种常用的处方药和非处方药被认为具有抗肿瘤特性和/或可能与多西他赛存在药代动力学相互作用，从而降低化疗效果。
为了在该试验中研究药物对前列腺癌预后的影响，我们考察了14类药物（包括二甲双胍、地高辛、维拉帕米、质子泵抑制剂、硝酸盐类、他汀类、环氧化酶-2抑制剂、华法林、肝素、抗坏血酸、硒、生育酚、抗抑郁药和促红细胞生成素）对总生存期、前列腺特异性抗原（PSA）反应、PSA降低百分比、疼痛反应和生活质量反应的影响。
我们的研究结果未显示任何药物与多西他赛具有显著的相加或协同作用。然而，我们确实注意到，服用地高辛或维拉帕米的患者总生存期较差，这可能是由于维拉帕米组接受化疗的周期数较少，这与药代动力学相互作用一致。
鉴于统计局限性，这些数据仅用于提出假设，但可能为未来其他恶性肿瘤的类似分析奠定基础。数据表明需要注意与可能与多西他赛相互作用的药物之间的药代动力学相互作用。
