Impact of Carboplatin-Free Interval on Hypersensitivity Risks in Solid Tumor Patients with Silent Sensitization

Carboplatin hypersensitivity reactions (HSRs) often occur after silent sensitization in patients with solid tumors through repeated uneventful exposures. The carboplatin-free interval (CFI) has been implicated in HSR risk, but its independent impact on previously asymptomatic yet sensitized patients, as well as temporal risk patterns, remain unclear. We aimed to identify risk factors for HSRs following carboplatin re-administration in patients who had completed prior carboplatin treatment without HSRs, and to clarify the temporal association between CFI and HSR risk.

We retrospectively analyzed patients with solid tumors who received carboplatin after CFI ≥2 months at Seoul National University Hospital (2014-2016), excluding those with prior HSRs. Multivariable logistic regression identified factors associated HSRs. HSR incidence and severity were assessed across CFI strata (<12, 12-24, 24-36, ≥36 months).

: Among 258 patients with previous uneventful exposure, 52 (20.2%) developed HSRs, including 15 (5.8%) severe cases. Independent risk factors were female sex (odds ratio [OR] 6.105; p = 0.015), history of drug allergy (OR 2.991; p = 0.005), and CFI ≥12 months (OR 2.198; p = 0.030). Overall HSR incidence peaked at 33.3% with CFIs of 24-36 months, whereas severe HSRs were rare within 12 months but became progressively more frequent with longer CFIs, reaching the highest proportion beyond 36 months.

Longer CFI independently increases the risk of carboplatin-induced HSRs. These findings support using CFI as a predictor for individualized risk assessment, particularly for patients re-administered after CFIs of 24-36 months, who may warrant closer monitoring and preventive strategies.