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

Br J Cancer. 2021 May;124(10):1647-1652. doi: 10.1038/s41416-021-01313-0. Epub 2021 Mar 24.

Abstract

Background: Ranitidine, a histamine 2 blocker, is the standard of care to prevent hypersensitivity reactions (HSRs) caused by paclitaxel infusion. However, the added value of ranitidine in this premedication regimen is controversial. Therefore, we compared the incidence of HSRs during paclitaxel treatment between a standard regimen including ranitidine and a regimen without ranitidine.

Methods: This prospective, pre-post interventional, non-inferiority study compared 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. Non-inferiority was determined by checking whether the upper bound of the two-sided 90% confidence interval (CI) for the difference in HSR rates excluded the +6% non-inferiority margin.

Results: In both the pre-intervention (with ranitidine) and post-intervention (without ranitidine) group 183 patients were included. 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 to 0.1).

Conclusions: As the upper boundary of the 90% CI does not exceed the predefined non-inferiority margin of +6%, it can be concluded that a premedication regimen without ranitidine is non-inferior to a premedication regimen with ranitidine.

Clinical trial registration: www.trialregister.nl ; NL8173.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chemoprevention / adverse effects
  • Chemoprevention / methods
  • Clemastine / administration & dosage
  • Dexamethasone / administration & dosage
  • Drug Hypersensitivity / epidemiology
  • Drug Hypersensitivity / pathology
  • Drug Hypersensitivity / prevention & control*
  • Drug Therapy, Combination
  • Equivalence Trials as Topic
  • Female
  • Histamine H2 Antagonists / administration & dosage
  • Histamine H2 Antagonists / therapeutic use
  • Humans
  • Infusions, Intravenous
  • Male
  • Medical Futility
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / epidemiology
  • Neoplasms / pathology
  • Netherlands / epidemiology
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects*
  • Premedication / adverse effects
  • Premedication / methods*
  • Ranitidine / administration & dosage
  • Ranitidine / therapeutic use*
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Histamine H2 Antagonists
  • Dexamethasone
  • Ranitidine
  • Clemastine
  • Paclitaxel