Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Division of Hematology/Oncology, Department of Medicine, University of California San Diego, Moores Cancer Center, La Jolla, CA.
Clin Genitourin Cancer. 2017 Dec;15(6):724-732. doi: 10.1016/j.clgc.2017.05.019. Epub 2017 May 31.
Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion and can affect the optimal absorption of concomitant oral medications, such as vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs). The purpose of this study was to investigate the effect of PPI use on survival in metastatic renal cell carcinoma (mRCC) patients treated in the targeted therapy era.
We conducted a pooled analysis of mRCC patients treated in phase II and III clinical trials. Statistical analyses were performed using Cox regression adjusted for several risk factors and the Kaplan-Meier method.
We identified 2188 patients treated with sunitinib (n = 952), axitinib (n = 626) or sorafenib (n = 610), of whom 120 were PPI users. Overall, PPI users showed similar overall survival compared with non-PPI users (hazard ratio [HR], 1.051; 95% confidence interval [CI], 0.769-1.438; P = .754; median, 24.1 vs. 21.3 months). Similarly, progression-free survival (HR, 1.016; 95% CI, 0.793-1.301; P = .902; median, 5.5 vs. 8.0 months) and objective response rates (23.3% vs. 27.4%; P = .344) were not different between PPI users and nonusers. These findings were consistent across International mRCC Database Consortium risk groups and according to line of therapy. Adverse events were similar between PPI users and nonusers.
We showed that PPI use does not appear to negatively affect the efficacy and safety of select VEGF-TKIs in patients with mRCC. Documentation of concomitant medications and patient education on potential drug interactions are critical for optimizing the use of oral cancer-targeting therapy.
质子泵抑制剂（PPIs）是一种强效胃酸分泌抑制剂，可能会影响同时服用的口服药物（如血管内皮生长因子（VEGF）酪氨酸激酶抑制剂（TKI））的最佳吸收。本研究旨在探讨在靶向治疗时代接受治疗的转移性肾细胞癌（mRCC）患者中，使用 PPI 对生存的影响。
我们对接受 II 期和 III 期临床试验治疗的 mRCC 患者进行了汇总分析。使用 Cox 回归调整了多个危险因素，并采用 Kaplan-Meier 法进行了统计分析。
我们共纳入了 2188 例接受舒尼替尼（n=952）、阿昔替尼（n=626）或索拉非尼（n=610）治疗的患者，其中 120 例为 PPI 使用者。总体而言，与非 PPI 使用者相比，PPI 使用者的总生存期相似（风险比 [HR]，1.051；95%置信区间 [CI]，0.769-1.438；P=0.754；中位数，24.1 与 21.3 个月）。同样，无进展生存期（HR，1.016；95%CI，0.793-1.301；P=0.902；中位数，5.5 与 8.0 个月）和客观缓解率（23.3%与 27.4%；P=0.344）在 PPI 使用者和非使用者之间也无差异。这些发现与国际 mRCC 数据库联盟风险组一致，且与治疗线无关。PPI 使用者和非使用者之间的不良反应相似。
我们表明，在转移性肾细胞癌患者中，使用 PPI 似乎不会对选择的 VEGF-TKI 的疗效和安全性产生负面影响。记录同时使用的药物并对潜在药物相互作用进行患者教育对于优化口服癌症靶向治疗的使用至关重要。
