NCIC Clinical Trials Group, Queens University, 10 Stuart Street, Kingston, Ontario, Canada K7L-3N6.
Lung Cancer. 2013 Oct;82(1):136-42. doi: 10.1016/j.lungcan.2013.06.008. Epub 2013 Jul 31.
As the bioavailability of erlotinib is dependent on gastric pH, an increase in gastric pH via the concurrent use of gastric acid suppressive medications (AS) may reduce its bioavailability and efficacy. We retrospectively analyzed the BR.21 trial database to pragmatically evaluate the impact of AS use on the median plasma drug levels of erlotinib, adverse events and outcome of participants.
Monthly median plasma levels of erlotinib were compared between participants utilizing AS and those who did not using a Wilcoxon test. Interaction p-value for AS users and AS non-users was performed using a multivariate Cox model with a time-dependent covariate for AS use. Grade 2 adverse events were compared using Fisher's Exact Test.
The median plasma erlotinib level was not significantly different between AS users and AS non-users, and AS use did not appear to incur a negative impact on PFS or OS (Interaction p-values: PFS p = 0.16; OS p = 0.81). AS users receiving erlotinib had a similar frequency of rash (50.5% vs. 42.0%, p = 0.08) and a statistically higher rate of diarrhea (27.9% vs. 15.6%, p = 0.001) compared to AS non-users. In addition, AS users had higher rates of infections (erlotinib arm: 33.7% vs. 20.0%, p < 0.0001; placebo arm: 22.7% vs. 10.8%, p = 0.02).
This retrospective analysis found that the co-administration of AS and erlotinib did not appear to have a significant impact on the median plasma drug levels or outcome.
厄洛替尼的生物利用度取决于胃内 pH 值，因此同时使用胃酸抑制药物（AS）可能会降低其生物利用度和疗效。我们回顾性分析了 BR.21 试验数据库，以实用的方式评估 AS 使用对厄洛替尼中位血浆药物水平、参与者不良反应和结局的影响。
采用 Wilcoxon 检验比较使用 AS 和未使用 AS 的参与者的每月中位血浆厄洛替尼水平。采用多变量 Cox 模型，使用 AS 使用的时间依赖性协变量对 AS 使用者和 AS 非使用者进行交互 p 值检验。采用 Fisher's Exact Test 比较 2 级不良事件。
AS 使用者和 AS 非使用者的中位血浆厄洛替尼水平无显著差异，AS 使用似乎并未对 PFS 或 OS 产生负面影响（交互 p 值：PFS p = 0.16；OS p = 0.81）。接受厄洛替尼治疗的 AS 使用者皮疹发生率（50.5%比 42.0%，p = 0.08）与 AS 非使用者相似，但腹泻发生率（27.9%比 15.6%，p = 0.001）统计学上更高。此外，AS 使用者的感染发生率更高（厄洛替尼组：33.7%比 20.0%，p < 0.0001；安慰剂组：22.7%比 10.8%，p = 0.02）。
这项回顾性分析发现，AS 与厄洛替尼联合使用似乎对中位血浆药物水平或结局没有显著影响。
