Intravenous prophylaxis for paclitaxel-related hypersensitivity reactions

Severe hypersensitivity reactions to paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) were reported during early phase I trials. A premedication regimen consisting of oral steroids 12 and 6 hours before treatment with paclitaxel as well as immediate infusion of diphenhydramine and cimetidine (or ranitidine) before paclitaxel markedly decreased the incidence of hypersensitivity reactions. Subsequently, investigators at the Fox Chase Cancer Center used intravenous dexamethasone, diphenhydramine, and cimetidine immediately before paclitaxel in an effort to obviate the inconvenience of oral steroid administration. Two prospective clinical trials that use carboplatin and paclitaxel were performed in patients with ovarian cancer and in patients with non-small cell lung cancer. In both these trials, all premedication for hypersensitivity reactions was administered intravenously immediately before paclitaxel. No significant hypersensitivity reactions were reported in these two trials, and, subsequently, a large retrospective search of a computerized pharmacy database concluded that a single-dose regimen of intravenous dexamethasone, diphenhydramine, and cimetidine is a safe and convenient alternative for prevention of hypersensitivity reactions associated with outpatient paclitaxel administration.