Nieves Sedano Marcos, Manuel Caro Teller José, García Muñoz Carmen, Fernandez Redondo Delia, Ponce Aix Santiago, Menéndez Orenga Miguel, Miguel Ferrari Piquero José
Department of Pharmacy, University Hospital 12 de Octubre, Madrid, Spain.
J BUON. 2018 May-Jun;23(3):647-653.
Erlotinib and gefitinib are both tyrosine kinase inhibitors (TKIs) approved for the treatment of non-small cell lung cancer (NSCLC). Although it is well known that the increase of gastric pH may decrease the solubility of TKIs, there is limited evidence about the clinical repercussion of this fact. The purpose of this study was to determine if the use of gastric acid suppressive therapy (As) concomitantly with TKIs has an adverse impact on progression-free survival (PFS) and to determine whether the type of drug used (proton pump inhibitors/PPIs or histamine-2 receptors antagonists (H2RAs) may influence it.
In this retrospective observational study included were patients treated for ≥1 week with erlotinib or gefitinib from January 2012 to December 2015. Demographic, diagnostic and therapeutic variables were collected. Patients were divided into two groups (As users and non-As users). For the calculation of the PFS the Kaplan Meier and multivariate Cox regression analysis were used.
163 patients with mean age 70 years were included. 72.397percnt; (n=118) received TKIs and As concomitantly. The mean PFS was 84 days (95% CI, 65-101) and 221 days (95% CI, 125-429; p <0.0001) in As users and non-As users, respectively. Regarding the type of As used, no significant differences were observed.
Concomitant use of As and TKIs adversely impacted the PFS outcomes in NSCLC patients regardless of the type of As used. Further studies are needed to determine the clinical impact of interactions between antiacids and antineoplastics.
厄洛替尼和吉非替尼均为获批用于治疗非小细胞肺癌（NSCLC）的酪氨酸激酶抑制剂（TKIs）。尽管众所周知胃内pH值升高可能会降低TKIs的溶解度，但关于这一事实的临床影响的证据有限。本研究的目的是确定同时使用胃酸抑制治疗（As）与TKIs是否会对无进展生存期（PFS）产生不利影响，并确定所使用药物的类型（质子泵抑制剂/PPIs或组胺-2受体拮抗剂（H2RAs））是否会对其产生影响。
在这项回顾性观察研究中，纳入了2012年1月至2015年12月期间接受厄洛替尼或吉非替尼治疗≥1周的患者。收集了人口统计学、诊断和治疗变量。患者分为两组（使用As组和未使用As组）。使用Kaplan Meier法和多变量Cox回归分析来计算PFS。
纳入了163例平均年龄为70岁的患者。72.397%（n = 118）的患者同时接受了TKIs和As治疗。使用As组和未使用As组的平均PFS分别为84天（95%CI，65 - 101）和221天（95%CI，125 - 429；p < 0.0001）。关于所使用As的类型，未观察到显著差异。
无论所使用As的类型如何，同时使用As和TKIs均对NSCLC患者的PFS结果产生不利影响。需要进一步研究以确定抗酸剂与抗肿瘤药之间相互作用的临床影响。
