Chu Michael P, Ghosh Sunita, Chambers Carole R, Basappa Naveen, Butts Charles A, Chu Quincy, Fenton David, Joy Anil A, Sangha Randeep, Smylie Michael, Sawyer Michael B
Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
Department of Pharmacy, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.
Clin Lung Cancer. 2015 Jan;16(1):33-9. doi: 10.1016/j.cllc.2014.07.005. Epub 2014 Aug 15.
Erlotinib is a key therapy for advanced NSCLC. Concurrent AS therapy with TKIs might reduce TKI plasma levels. Because of gastroesophageal reflux disease prevalence, this retrospective analysis was undertaken to determine if coadministering erlotinib with AS therapy affected NSCLC outcomes.
Records of advanced NSCLC patients who received erlotinib from 2007 to 2012 at a large, centralized, cancer institution were retrospectively reviewed. Pertinent demographic data were collected and concomitant AS treatment was defined as AS prescription dates overlapping with ≥ 20% of erlotinib treatment duration. Records of patients who received erlotinib for ≥ 1 week were analyzed for progression-free survival (PFS) and overall survival (OS).
Stage IIIB/IV NSCLC patients (n = 544) were identified and 507 had adequate data for review. The median age was 64 years and 272 were female. Adenocarcinoma (n = 318; 64%) and squamous (n = 106; 21%) were predominant subtypes; 124 patients received concomitant AS therapy. In this unselected population, median PFS and OS in AS versus no AS groups were 1.4 versus 2.3 months (P < .001) and 12.9 versus 16.8 months (P = .003), respectively. Factoring sex, subtype, and performance status in multivariate Cox proportional hazards ratios for PFS and OS between AS and no AS groups were 1.83 (95% confidence interval [CI], 1.48-2.25) and 1.37 (95% CI, 1.11-1.69), respectively.
This large population-based study suggests erlotinib efficacy might be linked with gastric pH and OS could be adversely affected. To our knowledge, this is the first study demonstrating a possible negative clinical effect of coadministration of erlotinib with AS therapy. Further prospective investigation is warranted.
厄洛替尼是晚期非小细胞肺癌（NSCLC）的关键治疗药物。酪氨酸激酶抑制剂（TKIs）与抗酸剂（AS）联合治疗可能会降低TKIs的血浆水平。鉴于胃食管反流病的患病率，进行了这项回顾性分析，以确定厄洛替尼与AS联合治疗是否会影响NSCLC的治疗结果。
回顾性分析了2007年至2012年在一家大型集中式癌症机构接受厄洛替尼治疗的晚期NSCLC患者的记录。收集了相关的人口统计学数据，将同时进行的AS治疗定义为AS处方日期与厄洛替尼治疗持续时间的≥20%重叠。对接受厄洛替尼治疗≥1周的患者记录进行无进展生存期（PFS）和总生存期（OS）分析。
共确定了IIIB/IV期NSCLC患者（n = 544），其中507例有足够的数据可供审查。中位年龄为64岁，女性272例。腺癌（n = 318；64%）和鳞癌（n = 106；21%）是主要亚型；124例患者接受了同时进行的AS治疗。在这个未经过选择的人群中，AS组与非AS组的中位PFS分别为1.4个月和2.3个月（P <.001），中位OS分别为12.9个月和16.个月（P =.003）。在多变量Cox比例风险模型中，将性别、亚型和体能状态纳入分析后，AS组与非AS组PFS和OS的风险比分别为1.83（95%置信区间[CI]，1.48 - 2.25）和1.37（95%CI，1.11 - 1.69）。
这项基于大量人群的研究表明，厄洛替尼的疗效可能与胃内pH值有关，且OS可能受到不利影响。据我们所知，这是第一项证明厄洛替尼与AS联合治疗可能产生负面临床效果的研究。有必要进行进一步的前瞻性研究。
