Survival impact of concomitant use of proton pump inhibitors among patients receiving adjuvant chemotherapy for stage III colon cancer

Prior studies suggest concomitant use of proton pump inhibitors (PPIs) may reduce the efficacy of oral capecitabine through impaired absorption, with no interaction expected with intravenous 5-fluorouracil (5-FU). A study using the Australian Comprehensive Cancer Outcomes and Research Database (ACCORD) investigated the survival impact of concomitant use of PPI in patients receiving adjuvant chemotherapy for stage III colon cancer between 2006 and 2023. A total of 459 patients were included: 63 (14%) received 5-FU alone, 115 (25%) capecitabine alone, 148 (32%) FOLFOX, and 133 (29%) CAPOX. High-risk disease (T4 and/or N2) was present in 203 patients (44%). Overall, 142 patients (31%) received a PPI during adjuvant chemotherapy, with similar rates across treament groups (p=0.952). Formal interaction testing did not demonstrate significant heterogeneity of PPI effect across treatment regimens. However, in high-risk patients receiving CAPOX, PPI use was associated with reduced recurrence-free survival (HR 3.07; p=0.006) and overall survival (HR 4.11; p=0.008). No impact was observed with capecitabine monotherapy, 5-FU, or FOLFOX. The authors conclude that concomitant PPI use is common in Australian patients with stage III colon cancer. While formal interaction testing did not reach statistical significance, PPI use was associated with inferior survival outcomes in high-risk patients receiving CAPOX.