Prophylactic effect of pemirolast, an antiallergic agent, against hypersensitivity reactions to paclitaxel in patients with ovarian cancer

Abstract

We have previously shown that sensory nerve peptides contribute to the pathogenesis of pulmonary hypersensitivity reactions (HSRs) to paclitaxel in rats. Moreover, pemirolast, an antiallergic agent, reverses the HSRs to paclitaxel, although the mechanism is considered to result from the blockade of paclitaxel-induced release of sensory peptides, rather than the inhibition of histamine release. In the present study, we investigated the preventive effect of pemirolast against acute HSRs in a total of 84 patients who undertook postoperative paclitaxel plus carboplatin chemotherapy every 4 weeks for ovarian cancer. Patients were assigned to receive oral lactose (placebo) or pemirolast (10 mg), 2 hr before paclitaxel infusion. All patients received conventional premedication, including oral diphenhydramine, intravenous ranitidine and intravenous dexamethasone, 30 min before paclitaxel infusion. The HSRs that led to the discontinuance of paclitaxel infusion (grade>or=2) occurred in 5 of 42 patients in placebo group, whereas none of pemirolast-treated 42 patients showed any signs of HSRs. Plasma histamine concentrations were not changed after paclitaxel infusion in either group. Our present findings suggest that pemirolast is potentially useful for prophylaxis of paclitaxel-induced HSRs. In this respect, the use of pemirolast as premedication is expected to be beneficial to the safety management in patients who undergo chemotherapy containing paclitaxel.