Over-the-counter heartburn and gastrointestinal drugs, such as proton pump inhibitors (PPIs), may decrease the effectiveness of chemotherapy in patients with gastroesophageal cancer (GEC), according to a new study published in JAMA Oncology.
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Capecitabine, a cytotoxic chemotherapeutic often prescribed to patients with GEC, is administered orally. However, as with other oral medications, the introduction of PPIs such as Nexium, Prevacid, or Protonix, could impair the absorption of capecitabine and reduce its effects. Patients with cancer may not have these medications prescribed by their physicians, but may obtain them over-the-counter at a pharmacy. Up to 20% of cancer patients could be taking PPIs and accidentally altering their capecitabine treatment.
Researchers led by Michael B Sawyer, MD, and Michael P Chu, MD, Cross Cancer Institute, Department of Oncology, University of Alberta (Canada), conducted a secondary analysis of a trial to determine if gastric acid suppressants, such as PPIs, impair capecitabine efficacy. The trial was a phase III, randomized comparison of capecitabine and oxaliplatin (CapeOx) with or without lapatinib in 545 patients with ERBB2/human epidermal growth factor receptor 2-positive metastatic GEC from 2008-2012. A total of 229 (42%) patients received PPIs. Efficacy was determined by comparing progression-free survival (PFS) and overall survival (OS) between patients treated with PPIs vs patients who were not.
Results of the analysis showed negative effects of PPIs in capecitabine treatment. Patients who received CapeOx without lapatinib had poorer median PFS (4.2 vs 5.7 months, hazard ratio [HR]: 1.55; 95% CI, 1.29-1.81, P <0 .001) and poorer median OS (9.2 vs 11.3 months, HR: 1.34; 95% CI, 1.06-1.62; P = 0.04). Patients who received CapeOx with lapatinib were less effected by PPIs; PFS (HR: 1.08; P=0.54) and OS (HR: 1.26; P=0.10) were deemed clinically insignificant.
Researchers concluded that PPIs may negatively affect capecitabine efficacy by raising gastric pH levels, which leads to altered dissolution and absorption. Whether PPIs affect lapatinib is unclear given concurrent capecitabine, but researchers still caution against prescribing PPIs to patients. “Physicians should use caution in prescribing PPIs to patients on capecitabine and, if they must use PPIs due to gastrointestinal bleeding issues, maybe they should consider using other types of chemotherapy that don't present this interaction," said Dr Sawyer.
Further studies are under way to determine PPIs’ impact in capecitabine treatment for breast cancer and colon cancer. Capecitabine is often prescribed to patients with these types of cancers.
