Clinical predictors of breakthrough reactions during initial rapid drug desensitizations to platinum chemotherapeutics

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Background: Rapid drug desensitizations (RDD) provide a means for patients with a history of acute hypersensitivity reactions (HSR) to platinum-based chemotherapeutics to continue their first-line oncologic treatment. Approximately one third of RDDs have been associated with breakthrough reactions (BTR) but identifying which patients are at risk is challenging. Objective: The objective was to identify factors predictive of patients at risk of developing BTR during their initial RDD. Methods: Forty-three patients who developed HSRs to a platinum drug and subsequently underwent RDDs were included for analysis. A retrospective manual chart review was performed to obtain demographics and information with regard to oncologic history, incident HSR, and RDD. The severity of HSRs and BTRs was determined by using the Brown criteria. Results: BTRs developed in 37% of patients during their initial RDD. Compared with those who tolerated RDDs, the patients who developed BTRs were significantly more likely to have positive allergy skin test results with a platinum drug (100%) than those who tolerated their RDD (47%, p = 0.01). The median (interquartile range) time between incident HSR and initial RDD was significantly shorter among patients who developed BTRs (31 days [21‐49 days]) than those who did not develop BTRs (46 days [28‐826 days]) (p = 0.04). Only 46% of patients with severe incident HSRs developed a BTR. However, severe BTRs occurred only in patients who had severe incident HSRs (p = 0.02). Conclusion: Severe clinical signs and symptoms of incident HSRs do not always predict if BTRs will occur during initial RDDs. However, patients with severe BTRs are more likely to have had a severe incident HSR.

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