Proton Pump Inhibitors Seem to Reduce the Efficacy of Capecitabine in Advanced Gastroesophageal Cancer

Key Points

  • Use of proton pump inhibitors was associated with worse progression-free and overall survival among patients receiving capecitabine/oxaliplatin.
  • On multivariate analysis, use of proton pump inhibitors was associated with worse overall survival among patients receiving capecitabine/oxaliplatin plus lapatinib.

In a secondary analysis of a clinical trial reported in JAMA Oncology, Chu et al found that use of proton pump inhibitors (gastric acid suppressants) reduced the effectiveness of oral capecitabine in patients with advanced gastroesophageal cancer.

The study involved analysis of the effect of exposure to proton pump inhibitors on outcomes in the TRIO-013/LOGiC trial, a phase III randomized trial comparing capecitabine and oxaliplatin (CapeOx) plus lapatinib (Tykerb) vs placebo in 545 patients with ERBB2/HER2-positive metastatic gastroesophageal cancer. Of the 545 patients, 229 (42%) received proton pump inhibitors and were balanced between the groups.


In the placebo group, patients treated with proton pump inhibitors had a poorer median progression-free survival (4.2 vs 5.7 months, hazard ratio [HR] = 1.55, P < .001) and overall survival (9.2 vs 11.3 months, HR = 1.34, P = .04) vs patients not treated with proton pump inhibitors. In multivariate analysis including age, race, disease stage, and sex, significantly poorer progression-free (HR = 1.68, P < .001) and overall survival (HR = 1.41, P = .001) were maintained in patients treated with proton pump inhibitors.

In the lapatinib group, there were no significant differences between patients receiving vs not receiving proton pump inhibitors in progression-free (HR = 1.08, P = .54) or overall survival (HR = 1.26, P = .10) on univariate analysis. On multivariate analysis, median overall survival was worse among patients treated with proton pump inhibitors overall (HR = 1.38, P = .03).

The investigators concluded: “Proton pump inhibitors negatively [affected] capecitabine efficacy by possibly raising gastric pH levels, leading to altered dissolution and absorption. These results are consistent with previous erlotinib and sunitinib studies. Whether [proton pump inhibitors] affected lapatinib is unclear given concurrent capecitabine. Given capecitabine’s prevalence in treatment of breast cancer and colon cancer, further studies are under way.”

Michael B. Sawyer, MD, of Cross Cancer Institute, Alberta Health Services, Edmonton, Alberta, Canada, is the corresponding author of the JAMA Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.




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