Premedication strategy for weekly paclitaxel

Dexamethasone and histamine antagonists have been employed commonly as premedications for prophylaxis of hypersensitivity reactions (HSRs) to paclitaxel. Frequent premedications for weekly administration of paclitaxel are associated with added side-effects and extra cost. We analyzed our experience of HSRs to paclitaxel administered every 3-4 weeks, and designed a treatment algorithm to eliminate premedications in a majority of patients receiving weekly paclitaxel.

The incidence of HSRs was analyzed retrospectively in patients who received 3-hr infusions of paclitaxel (135-225 mg/m2) every 3-4 weeks in our institution over a period of 5 years. On the basis of the results of this analysis, we designed a premedication schema for patients receiving weekly paclitaxel, 50-90 mg/m2/week, as follows: Thirty minutes prior to the first weekly dose of paclitaxel, patients received intravenously (i.v.) dexamethasone (10 mg), diphenhydramine (25 mg), and cimetidine (300 mg). If no HSRs occurred, all premedications were deleted for subsequent weekly paclitaxel doses. For patients who experienced HSRs, 20 mg of dexamethasone was given orally 12 and 6 hr prior to re-challenge with paclitaxel in addition to diphenhydramine and cimetidine.

Over a period of 5 years, 358 patients received 1608 3-hr infusions of paclitaxel (135-225 mg/m2). Hypersensitivity reactions, which occurred exclusively during the first cycle of paclitaxel administration, were observed in 14 patients. Of these 14 patients, 11 were successfully retreated with paclitaxel without HSRs, two had recurrent HSRs upon paclitaxel re-challenge, and one refused further treatment. These observations indicate that HSRs to paclitaxel occurred in 4% of patients upon first exposure, that most of these patients can be retreated successfully with paclitaxel without recurrent HSRs, and that if no HSRs occur during the first cycle, HSRs are unlikely to occur with subsequent paclitaxel administration. The premedication schema was applied to 30 patients receiving 205 one-hr infusions of weekly paclitaxel. Using this premedication strategy, no HSRs have been observed during the initial or subsequent administration of paclitaxel.

We conclude that this premedication strategy is feasible and worthy of further study for patients receiving weekly paclitaxel.