Successful desensitization to carboplatin in patients with systemic hypersensitivity reactions

Carboplatin is the drug of choice for the treatment of nonresectable astrocytomas in children, but patients who are intolerant may require cranial irradiation which is associated with significant morbidity. Hypersensitivity reactions, including urticaria, bronchospasm, and hypotension, have been reported in 1% to 30% of patients treated with carboplatin. Although a few patients have attempted to continue therapy following pretreatment with antihistamines and corticosteroids, most have had recurrent severe reactions and have discontinued therapy. Two children with a history of severe systemic reactions to carboplatin were pretreated with 1 to 2 mg/kg of oral prednisolone the night before and the morning of their infusion. The initial desensitization was carried out in the intensive care unit (ICU) using doses of 1, 2.5, 5, 10, 25, and 50 mg of carboplatin infused at 1 mg/min every 15 minutes. This was well-tolerated and the remainder of the dose was infused at the standard rate of 200 mg/hr. One patient continued to receive infusions in the clinic without any difficulty. The other patient tolerated a second infusion, but during his third he experienced a systemic reaction that required discontinuation of the infusion and treatment with diphenhydramine. Desensitization was repeated in the ICU with pretreatment with prednisolone, diphenhydramine, and ranitidine, starting with 0.1 mg of carboplatin, and increasing more slowly than in the first protocol. This was well-tolerated, and subsequent infusions have been administered beginning with 1 mg doses without adverse effects. Both boys continued therapy with carboplatin; their astrocytomas are stable and they are clinically well. The use of the desensitization protocol enabled them to avoid cranial irradiation and improved their chances for normal neurologic development.