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.
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.
摘要：
背景：质子泵抑制剂（PPI）由于其可负担性和最小的严重副作用而被广泛使用。然而,它们对癌症治疗效果的影响，特别是雄激素受体信号抑制剂（ARSI），尚不清楚。这项研究调查了PPI使用对转移性去势抵抗性前列腺癌（mCRPC）患者治疗结果的影响。
方法：对117例mCRPC患者进行回顾性分析，并根据ARSI治疗开始时合并使用PPI分为两组：PPI+（n=38）和PPI-（n=79）。患者特征,包括接受ARSI治疗的年龄，接受ARSI治疗时的前列腺特异性抗原（PSA）值，国际泌尿外科病理学学会前列腺活检分级组，接受ARSI治疗时的转移部位，先前的多西他赛（DTX）治疗，记录ARSI的类型（醋酸阿比特龙或恩扎鲁他胺）。无进展生存期（PFS），总生存期（OS），比较两组的PSA反应率。根据临床背景进一步对患者进行分层，以比较两组之间的PFS和OS。
结果：PPI组表现出显著延长的PFS和改善OS的趋势。对于PSA反应（从基线降低50%或更多），PPI-组和PPI+组的发生率分别为62.3%和45.9%，分别。对于深度PSA反应（比基线降低90%或更多），PPI-组和PPI+组的发生率分别为36.4%和24.3%，分别。通过先前的DTX治疗和所施用的ARSI的类型来划分亚组之间的效果是一致的。
结论：在mCRPC患者中服用PPI似乎会降低ARSI的疗效。需要进一步的前瞻性研究来证实这些发现并探索所涉及的生物学机制。
方法：对117例mCRPC患者进行回顾性分析，并根据ARSI治疗开始时合并使用PPI分为两组：PPI+（n=38）和PPI-（n=79）。患者特征,包括接受ARSI治疗的年龄，接受ARSI治疗时的前列腺特异性抗原（PSA）值，国际泌尿外科病理学学会前列腺活检分级组，接受ARSI治疗时的转移部位，先前的多西他赛（DTX）治疗，记录ARSI的类型（醋酸阿比特龙或恩扎鲁他胺）。无进展生存期（PFS），总生存期（OS），比较两组的PSA反应率。根据临床背景进一步对患者进行分层，以比较两组之间的PFS和OS。
结果：PPI组表现出显著延长的PFS和改善OS的趋势。对于PSA反应（从基线降低50%或更多），PPI-组和PPI+组的发生率分别为62.3%和45.9%，分别。对于深度PSA反应（比基线降低90%或更多），PPI-组和PPI+组的发生率分别为36.4%和24.3%，分别。通过先前的DTX治疗和所施用的ARSI的类型来划分亚组之间的效果是一致的。
结论：在mCRPC患者中服用PPI似乎会降低ARSI的疗效。需要进一步的前瞻性研究来证实这些发现并探索所涉及的生物学机制。
