A Randomized Controlled Trial Plus a Systematic Review and Meta-Analysis of Published Studies Evaluating a Conventional Prophylactic Regimen of Oral Dexamethasone vs Short-Course Intravenous Dexamethasone in Preventing Paclitaxel-Associated Hypersensitivity Reactions in Patients With Gynecologic Malignancies.

Abstract

Background: Hypersensitivity reactions (HSRs) are often encountered in patients receiving paclitaxel infusions. The conventional method, comprising dexamethasone 20 mg (Dex20) taken 12 and 6 hours before paclitaxel plus histamine (H)1 and H2-antagonists administered 30 minutes before paclitaxel, is an effective but cumbersome method in reducing HSRs in gynecologic oncology patients.

Objective: Determine the effectiveness of a simplified premedication method (short-course) comprising Dex20 and H1 and H2 antagonists administered 30 minutes before paclitaxel vs the conventional method in preventing HSRs.

Methods: The effectiveness of the short-course vs the conventional method was investigated via a Randomized Controlled Trial (RCT) and a Systematic Review and Meta-analysis by searching PubMed, EMBASE, and the Cochrane Library from inception to December 4, 2024. Primary outcomes were any-grade and grade ≥3 HSRs. Differences in effectiveness were presented as risk difference (RD) using the Mantel-Haenszel estimation and expressed with 95% confidence intervals (CIs). P-values <0.05 were considered statistically significant. The Cochrane Handbook for Systematic Reviews and Newcastle-Ottawa Score determined the quality of RCTs and observational studies.

Results: Three RCTs and 2 observational studies totaling 905 patients were analyzed. The short-course method showed a significantly higher incidence of any-grade HSRs than the conventional method (RD = 7%, 95% confidence interval [CI] = 0.3% to 12.8%, P = 0.04). Although in favor of the conventional method, there was no significant difference in grade ≥3 HSRs (RD = 2%, 95% CI = -0.4% to 4.8%, P = 0.09). Subgroup analyses of RCTs showed no significant differences in any-grade HSRs (RD = 6%, 95% CI = 0.3% to 12.8%, P = 0.39) or grade ≥3 HSRs (RD = 1%, 95% CI = -1.1% to 2.4%, P = 0.48).

Conclusion and relevance: The conventional method is favored over the short-course in preventing paclitaxel-associated HSRs. The short-course method is a plausible alternative for patients unable to comply with the conventional method's requirements. Included studies were either observational studies prone to bias and inconclusive inferences or RCTs, which may not be statistically powerful enough to produce reliable results. Larger sample size prospective studies are needed to authenticate findings.