Impact of proton pump inhibitors on the efficacy of androgen receptor signaling inhibitors in metastatic castration-resistant prostate cancer patients.

IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Prostate Pub Date : 2024-10-01 Epub Date: 2024-07-10 DOI:10.1002/pros.24769
Tokiyoshi Tanegashima, Masaki Shiota, Shigehiro Tsukahara, Jun Mutaguch, Shunsuke Goto, Satoshi Kobayashi, Takashi Matsumoto, Masatoshi Eto
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Abstract

Background: Proton pump inhibitors (PPIs) are widely used due to their affordability and minimal severe side effects. However, their influence on the efficacy of cancer treatments, particularly androgen receptor signaling inhibitors (ARSIs), remains unclear. This study investigates the impact of PPI usage on the treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods: A total of 117 mCRPC patients were retrospectively analyzed and divided into two groups based on the concomitant use of PPI at the initiation of ARSI treatment: PPI+ (n = 38) and PPI- (n = 79). Patient characteristics, including age at ARSI treatment administered, prostate-specific antigen (PSA) value at ARSI treatment administered, International Society of Urological Pathology grade group at prostate biopsy, metastatic site at ARSI treatment administered, prior docetaxel (DTX) treatment, and type of ARSI (abiraterone acetate or enzalutamide) were recorded. Progression-free survival (PFS), overall survival (OS), and PSA response rates were compared between the two groups. Patients were further stratified by clinical background to compare PFS and OS between the two groups.

Results: The PPI- group exhibited significantly extended PFS and a trend toward improved OS. For PSA response (reduction of 50% or more from baseline), the rates were 62.3% and 45.9% in the PPI- group and the PPI+ group, respectively. For deep PSA response (reductions of 90% or more from baseline), the rates were 36.4% and 24.3% in the PPI- group and the PPI+ group, respectively. The effects were consistent across subgroups divided by prior DTX treatment and type of ARSI administered.

Conclusions: The administration of PPIs appears to diminish the therapeutic efficacy of ARSIs in mCRPC patients. Further prospective studies are needed to confirm these findings and explore the biological mechanisms involved.

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质子泵抑制剂对转移性耐阉割前列腺癌患者雄激素受体信号抑制剂疗效的影响。
背景:质子泵抑制剂(PPIs)因其价格低廉、严重副作用小而被广泛使用。然而,它们对癌症治疗,尤其是雄激素受体信号转导抑制剂(ARSI)疗效的影响仍不清楚。本研究调查了PPI的使用对转移性抗性前列腺癌(mCRPC)患者治疗效果的影响:对117名mCRPC患者进行了回顾性分析,并根据患者在开始ARSI治疗时是否同时使用PPI分为两组:PPI+组(38人)和PPI-组(79人)。记录患者特征,包括接受ARSI治疗时的年龄、接受ARSI治疗时的前列腺特异性抗原(PSA)值、前列腺活检时的国际泌尿病理学会分级、接受ARSI治疗时的转移部位、之前接受的多西他赛(DTX)治疗以及ARSI类型(醋酸阿比特龙或恩杂鲁胺)。比较了两组患者的无进展生存期(PFS)、总生存期(OS)和PSA反应率。根据临床背景对患者进行进一步分层,比较两组患者的无进展生存期和总生存期:结果:PPI-组患者的PFS明显延长,OS呈改善趋势。PPI-组和PPI+组的PSA反应率(比基线降低50%或以上)分别为62.3%和45.9%。对于深度 PSA 反应(比基线降低 90% 或以上),PPI- 组和 PPI+ 组的比例分别为 36.4% 和 24.3%。根据之前的DTX治疗和ARSI类型划分的亚组效果一致:结论:服用 PPIs 似乎会降低 ARSIs 对 mCRPC 患者的疗效。需要进一步的前瞻性研究来证实这些发现并探索其中的生物学机制。
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来源期刊
Prostate
Prostate 医学-泌尿学与肾脏学
CiteScore
5.10
自引率
3.60%
发文量
180
审稿时长
1.5 months
期刊介绍: The Prostate is a peer-reviewed journal dedicated to original studies of this organ and the male accessory glands. It serves as an international medium for these studies, presenting comprehensive coverage of clinical, anatomic, embryologic, physiologic, endocrinologic, and biochemical studies.
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