Department of Pharmaceutical Sciences, Vanderbilt-Ingram Cancer Center and Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Department of Biostatistics, Vanderbilt-Ingram Cancer Center and Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Oncologist. 2018 Jun;23(6):686-692. doi: 10.1634/theoncologist.2017-0578. Epub 2018 Feb 27.
Pazopanib is an oral tyrosine-kinase inhibitor that is approved by the U.S. Food and Drug Administration for treatment of metastatic renal cell carcinoma (mRCC). Pharmacokinetic data have shown that concomitant administration of pazopanib and esomeprazole, a proton pump inhibitor (PPI), leads to decreased area under the curve and thus decreased exposure of pazopanib by 40%. Despite the pharmacokinetic data published to date, the clinical significance and impact on patient outcomes resulting from decreased pazopanib exposure remains unknown.
In this retrospective, observational, cohort study, 90 patients with mRCC who either received pazopanib in combination with a PPI or histamine 2 receptor antagonist (H2RA; concurrent PPI/H2RA group) or who did not take concurrent pH-elevating medications (no PPI/H2RA group) were compared to determine if there was an impact on progression-free survival (PFS), the primary endpoint, and secondary endpoints, overall survival (OS) and safety.
The differences between the PFS of 9.0 months and OS of 28.0 months for the concomitant PPI/H2RA group versus 11.0 months and 30.1 months, respectively, for the no PPI/H2RA group were not statistically significant. Rates of adverse events were similar between the concomitant PPI/H2RA and no PPI/H2RA groups.
Concomitant PPI or H2RA usage was not shown to be associated with a reduction in PFS or OS for patients receiving pazopanib for mRCC, with a similar toxicity profile in each group. Based on the results of this retrospective cohort study and the palliative nature of the treatment of patients with mRCC, clinicians should consider allowing patients to remain on concomitant pazopanib and acid-reducing therapy.
Pazopanib is a preferred category-one first-line treatment for predominant clear cell metastatic renal cell carcinoma (mRCC). However, because of an aging demographic, coupled with patients with mRCC presenting with multiple comorbidities, including symptomatic dyspepsia or gastroesophageal reflux disease, patients are commonly required to take pazopanib concomitantly with a proton pump inhibitor (PPI) or a histamine 2 receptor antagonist (H2RA). Despite earlier pharmacokinetic reports suggesting that an alkaline pH may result in poorer absorption, this institutional retrospective study found no effect on clinical outcomes. These data suggest that concurrent treatment of mRCC with pazopanib and a PPI or H2RA may be safe in everyday practice.
帕唑帕尼是一种口服酪氨酸激酶抑制剂，已获美国食品药品监督管理局批准用于治疗转移性肾细胞癌（mRCC）。药代动力学数据表明，帕唑帕尼与质子泵抑制剂（PPI）埃索美拉唑同时给药会导致曲线下面积减少，从而使帕唑帕尼的暴露量减少 40%。尽管迄今为止已发表了药代动力学数据，但降低帕唑帕尼暴露量对患者结局的临床意义和影响仍不清楚。
在这项回顾性、观察性队列研究中，90 名接受帕唑帕尼联合质子泵抑制剂或组胺 2 受体拮抗剂（同时使用 PPI/H2RA 组）或未同时使用升高 pH 值药物的 mRCC 患者（未使用 PPI/H2RA 组）进行了比较，以确定是否对无进展生存期（PFS）有影响，这是主要终点，以及次要终点，总生存期（OS）和安全性。
同时使用 PPI/H2RA 组的 PFS 为 9.0 个月，OS 为 28.0 个月，而未使用 PPI/H2RA 组的 PFS 分别为 11.0 个月和 OS 为 30.1 个月，差异无统计学意义。同时使用 PPI/H2RA 组和未使用 PPI/H2RA 组的不良事件发生率相似。
对于接受帕唑帕尼治疗的 mRCC 患者，同时使用 PPI 或 H2RA 并未显示与 PFS 或 OS 降低相关，两组的毒性特征相似。基于这项回顾性队列研究的结果和 mRCC 患者治疗的姑息性质，临床医生应考虑允许患者同时使用帕唑帕尼和降低胃酸的治疗。
帕唑帕尼是治疗主要为透明细胞的转移性肾细胞癌（mRCC）的首选一线治疗类别之一。然而，由于人口老龄化，再加上 mRCC 患者常伴有多种合并症，包括有症状的消化不良或胃食管反流病，患者通常需要同时服用帕唑帕尼和质子泵抑制剂（PPI）或组胺 2 受体拮抗剂（H2RA）。尽管早期的药代动力学报告表明碱性 pH 值可能导致吸收不良，但这项机构回顾性研究并未发现对临床结局有影响。这些数据表明，在日常实践中，同时使用帕唑帕尼和 PPI 或 H2RA 治疗 mRCC 可能是安全的。
