Dexamethasone Regimens for Prophylaxis of Paclitaxel-associated Hypersensitivity Reaction

Overview

Comparison of the efficacy and side effects of intravenous and oral regimens of dexamethasone for prophylaxis of paclitaxel-associated hypersensitivity reactions in primary ovarian, fallopian tube and peritoneal cancer patients receiving first cycle of combination paclitaxel and carboplatin.

The consensus statements on the management of ovarian cancer recommended intravenous paclitaxel (175 mg/m2 over 3 hr) plus intravenous carboplatin (area under the curve \[AUC\] 5.0-7.5 mg/ml∙min) given every 3 weeks for six cycles for first-line chemotherapy. A major limitation of paclitaxel was its poor water solubility, which led to the use of polyoxyethylated castor oil vehicle or Cremophor® EL as diluents resulted a hypersensitivity reactions (HSRs). Initial P-HSRs generally occur within 10 minutes of the start of paclitaxel infusion and most occur with the first or second infusion. Majority of patients manifest as minor symptoms characterized by flushing and rashes but sometime life-threatening characterized by generalized urticaria, angioedema, bronchospasm and hypertension or until fatal may occur. The reaction is likely due to the release of histamine and other vasoactive substances in response to Cremophor EL. Originally, the prophylactic regimen composed of the use of an oral corticosteroid administered in two doses at 12 and 6 hours prior to paclitaxel infusion accompanied with histamine receptor H1 and H2 antagonists administered intravenously 30 minutes prior to paclitaxel infusion was found to successfully limit P-HSRs denoted as "Conventional oral prophylactic regimen". While this three-drug prophylactic regimen has been shown to be effective, it can be inconvenient for patients because the oral corticosteroid must be taken 12 and 6 hours before chemotherapy administration. If the patient forgets to take one or both pretreatment steroid doses, it is not clear whether the patient can be safely treated. This led to the experimental prophylactic regimen of one dose of intravenous dexamethasone accompanied with the H1 and H2 antagonists administered 30 minutes prior to paclitaxel infusion was subsequently reported to be equivalent to the regimen of oral dexamethasone denoted as "Modified intravenous prophylactic regimen". This intravenous regimen results in lower total steroid doses and precludes the issues of compliance.

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