Isezaki Tatsuya, Yuyama Hitomi, Yasumuro Osamu, Miyaji Yasutomo, Funakoshi Ryohkan
Department of Pharmacy, Kameda Medical Center, 929 Higashi-Cho, Kamogawa, Chiba, 296-8602, Japan.
Department of Oncology, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba, 296-8602, Japan.
J Pharm Health Care Sci. 2025 Aug 18;11(1):76. doi: 10.1186/s40780-025-00477-8.
Pazopanib (PAZ) is an oral multi-kinase inhibitor used in the treatment of advanced soft tissue sarcoma. Gastric acid suppressants such as proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs) may reduce PAZ absorption by increasing gastric pH, potentially affecting its efficacy. This study aimed to evaluate the impact of concomitant use of acid suppressants on progression-free survival (PFS) and safety in patients with soft tissue sarcoma.
This retrospective study included patients with advanced or metastatic soft tissue sarcoma who were treated with PAZ at a single institution between 2015 and 2022. Patients were divided into two groups: those who received PAZ with concomitant acid suppressants (AS combination group) and those who did not (non-AS group). The primary outcome was PFS. Kaplan-Meier curves were used to estimate survival, and group differences were compared using the log-rank test. Multivariable Cox proportional hazards regression was performed to adjust for confounding factors.
A total of 99 patients were included (77 in the AS combination group, 22 in the non-AS group). The median PFS was 116 days in the AS combination group and 403 days in the non-AS group (hazard ratio [HR]: 1.42; 95% confidence interval [CI]: 0.68-2.85; P = 0.361). No statistically significant difference in PFS was observed. Adverse events of any grade occurred in 84% of patients in the AS combination group and 68% in the non-AS group. Grade ≥ 3 adverse events occurred in 33 patients (43%) in the AS combination group and 9 patients (41%) in the non-AS group.
In our cohort of sarcoma patients, the concomitant use of acid-suppressive agents was not associated with a statistically significant difference in PFS. However, the substantial numerical difference in median PFS observed between the groups (403 days vs. 116 days), coupled with the study's limited sample size, suggests a potentially clinically meaningful negative effect that warrants caution and further investigation in larger, prospective studies. Our findings, therefore, do not rule out a detrimental interaction and underscore the need for careful consideration when co-prescribing these agents with pazopanib in this patient population.
帕唑帕尼（PAZ）是一种口服多激酶抑制剂，用于治疗晚期软组织肉瘤。质子泵抑制剂（PPIs）和H2受体拮抗剂（H2RAs）等胃酸抑制剂可能会通过提高胃内pH值来降低PAZ的吸收，从而可能影响其疗效。本研究旨在评估同时使用胃酸抑制剂对软组织肉瘤患者无进展生存期（PFS）和安全性的影响。
这项回顾性研究纳入了2015年至2022年期间在单一机构接受PAZ治疗的晚期或转移性软组织肉瘤患者。患者分为两组：接受PAZ并同时使用胃酸抑制剂的患者（AS联合组）和未使用的患者（非AS组）。主要结局是PFS。采用Kaplan-Meier曲线估计生存率，并使用对数秩检验比较组间差异。进行多变量Cox比例风险回归以调整混杂因素。
共纳入99例患者（AS联合组77例，非AS组22例）。AS联合组的中位PFS为116天，非AS组为403天（风险比[HR]：1.42；95%置信区间[CI]：0.68 - 2.85；P = 0.361）。未观察到PFS有统计学显著差异。AS联合组84%的患者发生了任何级别的不良事件，非AS组为68%。AS联合组33例患者（43%）发生了≥3级不良事件，非AS组9例患者（41%）发生了此类事件。
在我们的肉瘤患者队列中，同时使用抑酸剂与PFS的统计学显著差异无关。然而，两组之间观察到的中位PFS存在较大数值差异（403天对116天），再加上该研究样本量有限，提示可能存在具有潜在临床意义的负面影响，这值得在更大规模的前瞻性研究中谨慎对待并进一步调查。因此，我们的研究结果不排除有害相互作用，并强调在该患者群体中将这些药物与帕唑帕尼联合处方时需要仔细考虑。
