实体瘤中与聚（ADP-核糖）聚合酶（PARP）抑制剂相关的内分泌和代谢异常的发生率及风险：一项荟萃分析。

Incidence and risk of endocrine and metabolic abnormalities linked to PARP inhibitors in solid tumors: a meta-analysis.

作者信息

Fu Shunlian, Zou Pingjin, Fang Zengyi, Zhou Xinxiang, Chen Junyang, Gong Cuicui, Quan Li, Lin Bing, Chen Qiu, Lang Jinyi, Chen Meihua

机构信息

Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, P.R. China.

Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, 610041, China.

出版信息

BMC Cancer. 2025 Jan 31;25(1):183. doi: 10.1186/s12885-025-13579-1.

DOI:10.1186/s12885-025-13579-1

PMID:39891102

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11783722/

Abstract

BACKGROUND

Poly (ADP-ribose) polymerase inhibitors (PARPi) serve as crucial therapeutic agents in solid tumor treatment. Preclinical investigations suggest a potential protective function of PARPi against endocrine and metabolic impairments. Nevertheless, the existing body of evidence remains inconclusive on this aspect.

PURPOSE

Our aim was to evaluate the potential impact of PARPi on endocrine and metabolic disruptions in clinical trials.

DATA SOURCES

We conducted a comprehensive search across the Medline, EMBASE, PubMed, and Web of Science databases, along with the ClinicalTrials.gov registry.

STUDY SELECTION

Phase II/III randomized controlled trials (RCTs) investigating the effects of PARPi in metabolic and endocrine processes were selected for inclusion in patients with solid tumors.

DATA EXTRACTION

The primary outcomes of interest encompassed metabolic and endocrine dysfunctions.

DATA SYNTHESIS

A total of 26 trials (n = 9,590 patients) were included in our meta-analysis. Niraparib demonstrated an increased risk of any-grade hyperglycemia (OR = 2.15, 95% CI 1.28-3.62), with patients receiving PARPi for metastatic pancreatic cancer showing a higher susceptibility to any-grade hyperglycemia (OR = 1.78, 95% CI 1.04-3.04). Conversely, rucaparib exhibited a potential ameliorative effect on hyperglycemia (OR = 0.54, 95% CI 0.30-0.97). No statistically significant disparities were observed for other outcomes associated with PARPi utilization.

LIMITATIONS

Among these RCTs included, 50% were assessed as low qualities due to high risk of bias.

CONCLUSIONS

Our meta-analysis demonstrated that PARPi may exert adverse effects on endocrine and metabolic pathways. Close monitoring of hyperglycemia is recommended for patients undergoing niraparib therapy, especially those with pancreatic cancer.

TRIAL REGISTRATION

This meta-Analysis was prospectively registered in the PROSPERO database with ID CRD42023457959.

摘要

背景

聚（ADP - 核糖）聚合酶抑制剂（PARPi）是实体瘤治疗中的关键治疗药物。临床前研究表明PARPi对内分泌和代谢损伤具有潜在的保护作用。然而，在这方面现有的证据仍然没有定论。

目的

我们的目的是在临床试验中评估PARPi对内分泌和代谢紊乱的潜在影响。

数据来源

我们对Medline、EMBASE、PubMed和Web of Science数据库以及ClinicalTrials.gov注册库进行了全面检索。

研究选择

选择调查PARPi对实体瘤患者代谢和内分泌过程影响的II/III期随机对照试验（RCT）纳入研究。

数据提取

感兴趣的主要结局包括代谢和内分泌功能障碍。

数据合成

我们的荟萃分析共纳入26项试验（n = 9590例患者）。尼拉帕利显示任何级别高血糖风险增加（比值比[OR] = 2.15，95%置信区间[CI] 1.28 - 3.62），接受PARPi治疗的转移性胰腺癌患者对任何级别高血糖的易感性更高（OR = 1.78，95% CI 1.04 - 3.04）。相反，鲁卡帕利对高血糖表现出潜在的改善作用（OR = 0.54，95% CI 0.30 - 0.97）。与PARPi使用相关的其他结局未观察到统计学上的显著差异。