Proton pump inhibition to prevent delayed chemotherapy-induced nausea and vomiting in patients receiving adjuvant or neoadjuvant breast cancer chemotherapy: a phase II, randomised double-blind crossover trial (PantoCIN).

PURPOSE

Delayed chemotherapy-induced nausea and vomiting (CINV) is a distressing effect of chemotherapy for early breast cancer (EBC), with rates exceeding 50%, despite multi-agent prophylaxis. We hypothesised that chemotherapy-induced alterations to the gastric environment may result in delayed CINV, and that pantoprazole, a proton pump inhibitor, may be effective prophylaxis by reducing stomach acid.

METHODS

Using a randomised crossover design, we compared pantoprazole 40 mg once daily with placebo for 5 days at the start of each chemotherapy cycle, in addition to standard antiemetic prophylaxis in previously untreated patients undergoing chemotherapy for EBC. The primary endpoint was complete absence of nausea and vomiting during days 2-5. Secondary endpoints included nausea scores using the MASCC Antiemesis Tool (MAT), number of episodes of vomiting and participant preference over the same period.

RESULTS

One hundred sixty participants were recruited from 10 New Zealand hospitals. There was a complete absence of delayed CINV in 51.4% of participants when taking pantoprazole versus 39.3% when taking placebo (OR = 2.2, 95% CI [1.18 to 4.12], P = 0.01). MAT scores for delayed nausea were significantly lower when participants were taking pantoprazole than when the same participants were taking placebo, P = 0.006. Pantoprazole was also preferred by 50.4% versus 25.2% preferring placebo, with no increase in adverse events.

CONCLUSIONS

Pantoprazole is a cost-effective and safe agent, which reduces rates of delayed nausea and should be considered as prophylaxis in patients undergoing emetogenic chemotherapy.

TRIAL REGISTRATION

The trial is registered in the US National Library of Medicine Clinical Trials Registry (Registration No. NCT03948477).