Association between prophylactic desloratadine use and docetaxel-induced skin toxicities in patients with early-stage breast cancer: an inverse probability-weighted retrospective cohort study.

PURPOSE: Docetaxel (DTX) causes skin toxicities despite dexamethasone-based supportive care, and no established adjunctive primary prophylaxis exists. We assessed whether desloratadine, a peripheral H1-receptor antagonist with anti-inflammatory properties, was associated with DTX-related skin toxicities in early-stage breast cancer.

METHODS

This single-center retrospective cohort included 143 patients with stage I-III breast cancer receiving perioperative DTX-based chemotherapy (75 mg/m2 every 3 weeks) with dexamethasone premedication. Desloratadine (5 mg daily from the morning after first DTX infusion through treatment completion) was prescribed nonrandomly to 49 patients (34.3%); 94 received no prophylactic antihistamine. The primary outcome was any patient-reported skin toxicity (rash, pruritus, or hand-foot syndrome [HFS]). The primary analysis used Hájek-normalized stabilized inverse probability of treatment weighting (IPTW), with 95% confidence intervals (CIs) from 2,000 patient-level bootstrap resamples with propensity-score refitting. Calendar-time confounding was assessed by post-implementation restriction.

RESULTS

After stabilized IPTW, skin-toxicity incidence was 46.2% with desloratadine and 70.7% without it (risk difference, - 24.6 percentage points; 95% CI, - 43.0 to - 5.3; risk ratio [RR], 0.65; 95% CI, 0.42-0.92). Descriptive estimates indicated lower pruritus incidence (RR, 0.36; 95% CI, 0.08-0.79), a lower but imprecise rash estimate (RR, 0.70; 95% CI, 0.43-1.03), and no lower HFS incidence (5.9% vs 5.4%). Post-implementation findings were similar (RR, 0.61; 95% CI, 0.42-0.90); negative-control neuropathy was not lower (RR, 1.19; 95% CI, 0.52-2.58).

CONCLUSION

Desloratadine prophylaxis was associated with lower skin-toxicity risk, particularly for pruritus. Rash risk was lower but imprecisely estimated; HFS risk was not lower. These hypothesis-generating findings warrant validation in a prospective randomized trial.