A member of a new class of antineoplastic agents (taxanes), paclitaxel is a natural diterpene product, isolated from the bark of Taxus brevifolia.
Clinically active in ovarian, breast and non-small lung cancer.
Severe reactions: 2%.
Hypersensitivity reactions: > 10%.
Bronchospasm, dyspnea (81%).
Urticaria, erythematous rash (74%).
Pneumonitis (in previously irradiated patients).
Basophil histamine release: non IgE-mediated response.
The vehicle (cremophor EL + ethanol) is likely to be responsible.
Premedication is effective. Numerous prophylactic regimens have been published:
- 1° 20 mg dexamethasone orally 12 hours and 6 hours before paclitaxel, and 20 mg I.V just before treatment + 50 mg diphenhydramine orally 12 hours and 6 hours before paclitaxel, and 50 mg I.V just before treatment + 25 mg ephedrine sulfate orally one hour before paclitaxel (if possible).
- 2° 5 to 20 mg dexamethasone I.V + 50 mg diphenhydramine I.V + 300 mg cimetidine or 50 mg ranitidine I.V 30 minutes before paclitaxel.
- 3° 20 mg dexamethasone I.V just before paclitaxel + 50 mg orphenadrine I.M, and 300 mg cimetidine I.V one hour before paclitaxel.
1/100000 (1, 2, 4, 8 ml) to 1 ml undiluted solution, then continuous infusion.
Alternative formulations of paclitaxel:
- polyethylene glycol (decreases the antitumor activity of taxol)
- cyclodextrins (renal and hemolytic toxicity)
- polyvinylpyrrolidone nanoparticles (improvement in antitumor efficacy)
- phospholipid suspensions: liposomes (increased efficacy)
Clinical efficacy needs to be established.