Proton pump inhibitors impair capecitabine efficacy

Last Updated: 2016-10-18

By Will Boggs MD

NEW YORK (Reuters Health) - Proton pump inhibitors (PPIs) impair capecitabine efficacy in patients with advanced gastroesophageal cancer, according to a secondary analysis of the TRIO-013/LOGiC trial.

"This could be a very common and underappreciated side effect," Dr. Michael B. Sawyer from Cross Cancer Institute, Edmonton, Alberta, Canada told Reuters Health by email. "One study estimated that 20% of cancer patients in general take proton pump inhibitors."

Capecitabine is an oral cytotoxic chemotherapeutic used to treat a variety of cancers.

Dr. Sawyer's team used data from the TRIO-013/LOGiC trial of capecitabine and oxaliplatin with or without lapatinib in patients with advanced and/or metastatic gastroesophageal cancer to evaluate whether the orally administered drugs capecitabine and/or lapatinib are influenced by concomitant PPI administration.

As reported October 13 online in JAMA Oncology, 42% of patients received PPIs, including 40% in the lapatinib arm and 43% in the control arm.

In the control arm, median progression-free survival (PFS) was significantly worse in patients treated with PPIs compared to those not treated with PPIs (4.7 vs 5.7 months); median overall survival was also worse with PPI treatment(9.2 vs 11.2 months).

In the lapatinib arm, however, there was no significant difference in median PFS with PPI treatment (5.7 vs 6.8 months), and no significant difference in overall survival (9.6 vs 13.6 months).

Multivariate analyses confirmed the adverse effect of PPIs on both PFS and overall survival in the control arm and the lack of adverse effect of PPIs in the lapatinib arm.

Patients in both groups treated without PPIs had a higher incidence of hand-foot syndrome, compared with patients treated with PPIs, but these differences fell short of statistical significance.

"Based on the initial findings of this study, we did a retrospective analysis of effects of proton pump inhibitors on the efficacy of adjuvant capecitabine in early stage colorectal cancer patients at our center," Dr. Sawyer said. "In univariate analysis, patients who took PPIs concurrently had a decreased recurrence free survival compared to patients who did not (74% vs 83%; p=0.03)). In multivariate analysis, there was a strong trend for decreased recurrence free survival in patients who took PPIs compared to patients who did not (Hazard Ratio=1.65, P=0.09)."

"Based on these findings physicians should use caution in prescribing PPIs to patients on capecitabine, and if they must use PPIs due to gastrointestinal bleeding issues, they maybe should consider using intravenous 5-flurouracil which will not be affected by this potential interaction," he said.

"Ideally a prospective study should be done to determine if PPIs interfere with the absorption and pharmacokinetics of capecitabine and other oral cytotoxic chemotherapeutics," Dr. Sawyer concluded.

SOURCE: http://bit.ly/2eCgcbc

JAMA Oncol 2016.