The impact of statin use on the efficacy of abiraterone acetate in patients with castration-resistant prostate cancer.
The impact of statin use on the efficacy of abiraterone acetate in patients with castration-resistant prostate cancer.
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DOI：
10.1002/pros.23390
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发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Kantoff PW
中科院分区：
文献类型：
--
作者：
Harshman LC;Werner L;Tripathi A;Wang X;Maughan BL;Antonarakis ES;Nakabayashi M;McKay R;Pomerantz M;Mucci LA;Taplin ME;Sweeney CJ;Lee GM;Kantoff PW
他汀类药物与DHEAS竞争通过SLCO2B1转运体流入，这可能延长雄激素剥夺治疗的进展时间（TTP）。醋酸阿比特龙（AA）也可能经历slco介导的转运。基于临床前研究结果显示的拮抗作用，我们假设他汀类药物可能通过SLCO2B1与AA竞争内流，并可能对药物疗效产生负面影响。我们查询了两个机构的临床数据库[丹娜-法伯癌症研究所（DFCI），约翰霍普金斯大学（JHU）]，以寻找接受AA治疗的CRPC患者。治疗时间是TTP的替代指标。使用Kaplan-Meier方法估计他汀类药物使用与AA持续时间之间的关系。多变量Cox回归模型校正已知预后因素。在纳入的224例DFCI和270例JHU患者中，大多数（96%）有转移性疾病。近一半（41%和45%）是他汀类药物使用者。在DFCI队列中，他汀类药物使用者的AA持续时间有延长的趋势：14.2个月对9.2个月（HR 0.79, 95% CI: 0.57-1.09, p=0.14）。在JHU队列中，他汀类药物的使用和AA持续时间之间没有关联：他汀类药物使用者和非他汀类药物使用者分别为8.3个月和8.0个月（HR 0.89, 95% CI: 0.69-1.16, p=0.38），除了之前未接受过多西他赛或恩杂鲁胺的患者（HR 0.79, 95% CI: 0.57-1.10）。与我们最初的假设相反，在整个DFCI队列中，他汀类药物使用者以及enzalutamide和docetaxel-naïve JHU患者的AA持续时间有更长（而不是更短）的趋势。总之，这些结果不支持他汀类药物干扰AA疗效的假设。
Statins compete with DHEAS for influx through the SLCO2B1 transporter, which may prolong time to progression (TTP) on androgen deprivation therapy. Abiraterone acetate (AA) may also undergo SLCO-mediated transport. Based on preclinical findings showing antagonism, we hypothesized that statins may compete with AA for influx via SLCO2B1 and could negatively impact drug efficacy. We queried two institutional clinical databases [Dana-Farber Cancer Institute (DFCI), Johns Hopkins University (JHU)] for CRPC patients treated with AA. Treatment duration was a surrogate for TTP. Associations between statin use and AA duration were estimated using the Kaplan-Meier method. Multivariable Cox regression modeling adjusted for known prognostic factors. Of the 224 DFCI and 270 JHU patients included, the majority (96%) had metastatic disease. Nearly half (41 and 45%) were statin users. In the DFCI cohort, there was a trend toward longer AA duration in statin users: 14.2 vs. 9.2 mo (HR 0.79, 95% CI: 0.57–1.09, p=0.14). There was no association between statin use and AA duration in the JHU cohort: 8.3 vs. 8.0 months (HR 0.89, 95% CI: 0.69–1.16, p=0.38) in the statin users vs. non-users, except for a trend in patients that had not previously received docetaxel or enzalutamide (HR 0.79; 95% CI: 0.57–1.10). Contrary to our initial hypothesis, there was a trend towards longer (rather than shorter) AA duration in statin users in the entire DFCI cohort and in the enzalutamide- and docetaxel-naïve JHU patients. Together, these results do not support the hypothesis that statins interfere with AA efficacy.
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影响因子：
28.4
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
通讯作者：
Kantoff PW
DOI：
10.1056/nejmoa1209096
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ryan CJ;Smith MR;de Bono JS;Molina A;Logothetis CJ;de Souza P;Fizazi K;Mainwaring P;Piulats JM;Ng S;Carles J;Mulders PF;Basch E;Small EJ;Saad F;Schrijvers D;Van Poppel H;Mukherjee SD;Suttmann H;Gerritsen WR;Flaig TW;George DJ;Yu EY;Efstathiou E;Pantuck A;Winquist E;Higano CS;Taplin ME;Park Y;Kheoh T;Griffin T;Scher HI;Rathkopf DE;COU-AA-302 Investigators
通讯作者：
COU-AA-302 Investigators
DOI：
10.1056/nejmoa1014618
发表时间：
2011-05-26
期刊：
The New England journal of medicine
影响因子：
--
作者：
de Bono JS;Logothetis CJ;Molina A;Fizazi K;North S;Chu L;Chi KN;Jones RJ;Goodman OB Jr;Saad F;Staffurth JN;Mainwaring P;Harland S;Flaig TW;Hutson TE;Cheng T;Patterson H;Hainsworth JD;Ryan CJ;Sternberg CN;Ellard SL;Fléchon A;Saleh M;Scholz M;Efstathiou E;Zivi A;Bianchini D;Loriot Y;Chieffo N;Kheoh T;Haqq CM;Scher HI;COU-AA-301 Investigators
通讯作者：
COU-AA-301 Investigators
影响因子：
3.9
作者：
Monbaliu, Johan;Gonzalez, Martha;Chien, Caly
通讯作者：
Chien, Caly
影响因子：
5.1
作者：
Tamae, Daniel;Mostaghel, Elahe;Montgomery, Bruce;Nelson, Peter S.;Balk, Steven P.;Kantoff, Philip W.;Taplin, Mary-Ellen;Penning, Trevor M.
通讯作者：
Penning, Trevor M.