<p>Concurrent proton-pump inhibitors increase risk of death for lung cancer patients receiving 1st-line gefitinib treatment - a nationwide population-based study</p>

Abstract

PurposeConcurrent proton pump inhibitor (PPI) use might reduce the plasma concentration of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Clinically, the adverse effect of PPIs on patients with non-small cell lung cancer (NSCLC) treated with first-line EGFR TKIs remains controversial. This study was conducted to evaluate whether the combined use of gefitinib with PPIs affected NSCLC outcomes.Patients and methodsWe performed a nationwide cohort study of patients newly diagnosed with NSCLC between 1997 and 2013 using the Taiwan Cancer Registry and Taiwan National Health Insurance databases. We identified patients who were treated with first-line EGFR TKIs and analyzed the association between use of PPIs and TKI treatment outcome. We defined the coverage ratio of PPIs as duration of PPI treatment in days divided by duration of TKIs in days. Patients who exhibited an overlap of >20% between PPI and TKI usage days were defined as having a high coverage ratio.ResultsA total of 1278 patients were treated with first-line gefitinib, 309 of which took PPIs at the same time and 145 had a high PPI coverage ratio. Patients had similar time to failure regardless of their PPI coverage ratio during gefitinib treatment. However, higher PPI coverage ratio significantly decreased overall survival (OS) compared with that of patients with a lower PPI coverage ratio or no PPI treatment in univariate analysis (median OS, 13.5, 16.7, and 21.8 months, respectively, p<0.01) and multivariate analyses (high coverage ratio HR: 1.67; low coverage ratio HR: 1.29). Exposure to PPIs during first line gefitinib treatment significantly decreased overall survival of patients with NSCLC.ConclusionConcurrent use of PPIs was associated with lower overall survival in patients with EGFR-mutant NSCLC under first-line gefitinib treatment.

Impact of Use of Gastric-Acid Suppressants and Oral Anti-Cancer Agents on Survival Outcomes: A Systematic Review and Meta-Analysis

“…A total of 353 potentially eligible records were identified in the electronic databases. After exclusion of n = 337 not pertinent papers, n = 16 were selected for inclusion in quantitative analysis (n = 372,418 patients included, with 12% of patients receiving concomitant GAS therapy) [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. The search results and characteristics of the included studies are presented in Figure 1 and Tables 1 and Table 2.…”

Crosstalk of physiological pH and chemical pKa under the umbrella of physiologically based pharmacokinetic modeling of drug absorption, distribution, metabolism, excretion, and toxicity

“…One example is gefitinib as the first-line of non-small cell lung cancer (NSCLC) treatment. It was shown that the clinical outcomes (progression-free survival and overall survival) are significantly affected when gastric acid-suppressing agents (such as Histamine-1 receptor antagonists or proton pump inhibitors) are co-administered [33,34]. Gefitinib is a weak base with a pH-dependent solubility, which leads to its higher solubility when the pH is less than 5.…”

Impact of Use of Gastric-Acid Suppressants and Oral Anticancer Agents on Survival Outcomes: A Systematic Review and Meta-Analysis

“…A total of 353 potentially eligible records were identified in the electronic databases. After exclusion of n=337 not pertinent papers, n=16 were selected for inclusion in quantitative analysis (n=372,418 patients included, with 12% of patients receiving concomitant GAS therapy) [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. The search results and characteristics of the included studies are presented in figure 1 and tables 1-2.…”