Statin Use at the Time of Initiation of Androgen Deprivation Therapy and Time to Progression in Patients With Hormone-Sensitive Prostate Cancer.
Statin Use at the Time of Initiation of Androgen Deprivation Therapy and Time to Progression in Patients With Hormone-Sensitive Prostate Cancer.
复制标题
DOI：
10.1001/jamaoncol.2015.0829
复制
发表时间：
2015-07
期刊：
影响因子：
28.4
通讯作者：
Kantoff PW
中科院分区：
文献类型：
--
作者：
Harshman LC;Wang X;Nakabayashi M;Xie W;Valenca L;Werner L;Yu Y;Kantoff AM;Sweeney CJ;Mucci LA;Pomerantz M;Lee GS;Kantoff PW
他汀类药物的使用与前列腺癌预后改善相关。硫酸脱氢表雄酮（DHEAS）是睾酮的前体，也是有机阴离子转运蛋白SLCO 2B1的底物。我们先前证明SLCO2B1的遗传变异与雄激素剥夺治疗（ADT）的疾病进展时间（TTP）相关。由于他汀类药物利用SLCO2B1进入细胞，我们假设它们可能与DHEAS摄取竞争，并且他汀类药物使用可能延长ADT时的TTP。使用前列腺癌细胞系的体外研究。对1996年1月至2013年11月期间接受ADT治疗的926例患者中他汀类药物使用情况的回顾性分析。学术，综合癌症中心。接受ADT治疗生化或转移性复发或原发转移性前列腺癌的患者。为了确定他汀类药物是否干扰DHEAS摄取，我们使用前列腺癌细胞系进行了体外研究。接下来，我们查询了我们的机构临床数据库，以评估他汀类药物使用与ADT治疗TTP之间的相关性。采用多变量考克斯回归估计TTP，并根据已知的预后因素进行调整。在体外，我们证明了他汀类药物通过竞争性结合SLCO2B1阻断DHEAS摄取。在我们的926例ADT队列中，283例（31%）在ADT开始时服用他汀类药物。中位随访5.8年后，644例患者（70%）在ADT治疗期间发生进展。ADT治疗的中位TTP为20.3个月（95% CI：18.24）。与非使用者相比，接受他汀类药物治疗的男性ADT的中位TTP较长（27.5 vs. 17.4个月，p=0.0005）。在调整预定义的预后因素后，这种关联仍然具有统计学意义[调整后的HR=0.83（p=0.039）]。在有和无转移的患者中均观察到他汀类药物的阳性效应。ADT开始时使用他汀类药物与ADT的TTP显著延长相关，即使在调整已知预后因素后也是如此。我们的体外研究发现，他汀类药物竞争性降低DHEAS摄取，从而有效地减少了可用的瘤内雄激素池，提供了一个合理的机制，支持他汀类药物使用者TTP延长的临床观察。
Statin use has been associated with improved prostate cancer outcomes. Dehydroepiandrosterone sulfate (DHEAS) is a precursor of testosterone and a substrate for SLCO2B1, an organic anionic transporter. We previously demonstrated that genetic variants of SLCO2B1 correlated with time to progression (TTP) on androgen deprivation therapy (ADT). Since statins utilize SLCO2B1 to enter cells, we hypothesized that they may compete with DHEAS uptake and that statin use might prolong TTP while on ADT. In vitro studies using prostate cancer cell lines. A retrospective analysis of statin use in 926 patients who had received ADT from January 1996 until November 2013. Academic, comprehensive cancer center. Patients who had received ADT for biochemical or metastatic recurrence or de novo metastatic prostate cancer. To determine if statins interfere with DHEAS uptake, we performed in vitro studies using prostate cancer cell lines. Next, we queried our institutional clinical database to assess for an association between statin use and TTP on ADT. TTP was estimated using multivariable Cox regression and adjusted for known prognostic factors. In vitro, we demonstrated that statins block DHEAS uptake by competitively binding to SLCO2B1. In our ADT cohort of 926 patients, 283 (31%) were taking a statin at ADT initiation. After a median follow-up of 5.8 years, 644 patients (70%) had progressed on ADT. Median TTP on ADT was 20.3 months (95% CI: 18,24). Men on statins had a longer median TTP on ADT compared to non-users (27.5 vs. 17.4 months, p=0.0005). The association remained statistically significant after adjusting for pre-defined prognostic factors [adjusted HR=0.83 (p=0.039)]. The positive statin effect was observed for both patients with and without metastases. Statin use at the time of ADT initiation was associated with a significantly longer TTP on ADT even after adjusting for known prognostic factors. Our in vitro findings that statins competitively reduce DHEAS uptake and thus, effectively decrease the available intratumoral androgen pool, affords a plausible mechanism to support the clinical observation of prolonged TTP in statin users.
登录
查看更多内容
影响因子：
3.7
作者：
Bansal D;Undela K;D'Cruz S;Schifano F
通讯作者：
Schifano F
影响因子：
10.3
作者：
Platz, Elizabeth A.;Leitzmann, Michael F.;Giovannucci, Edward
通讯作者：
Giovannucci, Edward
影响因子：
37.8
作者：
Weis, M;Heeschen, C;Cooke, JP
通讯作者：
Cooke, JP
DOI：
10.1158/1055-9965.epi-10-1023
发表时间：
2011-04
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Wright JL;Kwon EM;Ostrander EA;Montgomery RB;Lin DW;Vessella R;Stanford JL;Mostaghel EA
通讯作者：
Mostaghel EA
DOI：
10.1158/1940-6207.capr-09-0059
发表时间：
2010-01
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Zheng X;Cui XX;Gao Z;Zhao Y;Lin Y;Shih WJ;Huang MT;Liu Y;Rabson A;Reddy B;Yang CS;Conney AH
通讯作者：
Conney AH