Immediate hypersensitivity reaction to pegylated liposomal doxorubicin: management and outcome in four patients

Abstract

Hypersensitivity reactions (HSR) to pegylated liposomal doxorubicin (PLD; Caelyx^®) have been reported, and symptoms usually resolve with drug withdrawal. However, the risk of relapse of severe HSR and prevention remain poorly described. To report the management and outcome in four patients with HSR due to PLD. Patient characteristics, premedication regimen, rate of infusion, time between onset and HSR, clinical manifestations, and management were documented. A first cycle of PLD was received for cutaneous T-cell lymphoma (n = 3) and Kaposi sarcoma (n = 1). The drug was diluted in 250 mL 5% glucose and administered over one hour (4.17 mL dilution/min, i.e. 0.6 mg PLD/min for 1.8 m² body surface area [BSA]). Grade 3 HSR occurred in the first minutes in the four patients. Because of the absence of alternative treatment for the underlying disease, PLD was resumed. Premedication was reinforced with 300 mg oral ranitidine and 50 mg hydroxyzine the night before and the morning of infusion. The rate of infusion was 1 mL dilution/min (0.14 mg PLD/min for 1.8 m² BSA) for the first 15 minutes. No HSR occurred in three patients. In contrast, severe symptoms appeared in the first seconds of resumption in one patient. To minimise HSR to PLD, an initial reduced rate of infusion of 0.1-0.2 mg of PLD/min is warranted. In the event of HSR, alternative therapy must be privileged, and if necessary, careful re-challenge with PLD may be attempted, however relapse of HSR may occur.

Keywords: Kaposi sarcoma; allergy; cutaneous lymphoma; hypersensitivity; pegylated liposomal doxorubicin; pseudo-allergy.