The added value of H2-antagonists in premedication regimens during paclitaxel treatment

During our study on ranitidine as part of the paclitaxel-premedication regimen, there was a worldwide recall of ranitidine. Fortunately, at that time all of our patients were treated without ranitidine. The recall made the conclusions of our study even more relevant!
The added value of H2-antagonists in premedication regimens during paclitaxel treatment

Paclitaxel is one of the most commonly used anticancer drugs worldwide. To prevent HSRs, premedication regimens were introduced as standard of care during paclitaxel treatment and generally consists of the corticosteroid dexamethasone combined with a histamine 1 (H1)-receptor and the histamine 2 (H2)-receptor antagonist ranitidine. Although ranitidine is registered for the treatment of gastro-duodenal reflux and ulcer disease, it is also used for the prevention of allergic reactions during paclitaxel based chemotherapy. Strangely, the efficacy in preventing paclitaxel-associated HSRs has never been thoroughly studied and is therefore controversial. Therefore, we aimed to determine the added value of ranitidine in preventing clinically relevant HSRs by comparing the standard premedication regimen with ranitidine to an experimental premedication regimen without ranitidine. 

We conducted a prospective, pre-post interventional, non-inferiority study comparing the standard premedication regimen (N=183) with dexamethasone, clemastine and ranitidine with a premedication regimen without ranitidine (N=183). The primary outcome was the incidence of HSR grade ≥3 (as per Common Terminology Criteria for Adverse Events). The incidence of HSR grade ≥3 was 4.4% (N = 8) in the pre-intervention group and 1.6% (N = 3) in the post-intervention group: difference -2.7% (90% CI: -6.2%-0.1%). Resulting in the conclusion that a premedication regimen without ranitidine is non-inferior to a premedication regimen with ranitidine. 
This study shows that premedication regimens during anticancer treatment should be evaluated more critically. Their recommended use might not always be evidence-based and therefore may not be effective. Thus, more research is needed on the effectiveness, safety and proper dose of other premedication and co-medication drugs during anticancer therapy. Moreover, it should be considered to remove ranitidine from the paclitaxel labels and guidelines addressing the prevention of paclitaxel-induced HSR.

Coincidentally, while conducting this study, a worldwide recall of ranitidine was issued. This event has made the conclusions of this study even more relevant as ranitidine was omitted from the premedication regimen during paclitaxel infusion and an alternative was not available.