Hypersensitivity reactions taxane

Hypersensitivity reactions have occurred with all cancer chemotherapeutic agents. Reactions are most common with the taxanes, platinum compounds, asparaginases, and epipodophyllotoxins.7 Reactions range from mild (e.g., flushing and rashes) to severe (e.g., dyspnea, bronchospasm, urticaria, and hypotension). IgE-mediated type I reactions are the most common. To reduce the risk, patients are routinely pre-medicated... 

Docetaxel, another taxane, binds to tubulin to promote microtubule assembly. The pharmacokinetics of docetaxel are best described by a three-compartment model, with an a half-life of 0.08 hours, a 3 half-life of 1.6 to 1.8 hours, and a terminal half-life of 65 to 73 hours.14 Docetaxel has activity in the treatment of breast, non-small cell lung, prostate, bladder, esophageal, stomach, ovary, and head and neck cancers. Dexamethasone, 8 mg twice daily for 3 days starting the day before treatment, is used to prevent the fluid retention syndrome associated with docetaxel and possible hypersensitivity reactions. The fluid... 

Taxanes Fhclitaxel Neutropenia, peripheral neuropathy Alopecia, fluid retention, myalgia, skin reactions, ulceration necrosis with extravasation, bradycardia, stomatitis, hypersensitivity reactions... 

Monitor the patient for signs of hypersensitivity reactions to taxane or platinum chemotherapy regimens. 

Docetaxel -semisynthetic taxane stabilizes tubulin polymers leading to death of mitotic cells -bone marrow suppression -nausea and vomiting -mucocutaneous effects (mucositis, stomatitis, diarrhea) -hypersensitivity reactions -fluid retention syndrome -fatigue -myalgias -alopecia (universal)... 

Although not a taxane, ixabepilone is a novel microtubule inhibitor that was recently approved for metastatic breast cancer in combination with the oral fluoropyrimidine capecitabine or as monotherapy. It is a semisynthetic analog of epothilone B, and is active in the M phase of the cell cycle. This agent binds directly to 6-tubulin subunits on microtubules, leading to inhibition of normal microtubule dynamics. Of note, this agent continues to have activity in drug-resistant tumors that overexpress P-glycoprotein or tubulin mutations. The main adverse effects include myelosuppression, hypersensitivity reactions, and neurotoxicity in the form of peripheral sensory neuropathy. 

Low water solubility is a significant drawback to the therapeutic utility of the taxanes. This is particularly true of paclitaxel, which has a more lipophilic acetate moiety at Cio compared to docetaxel s more polar hydroxyl group. Paclitaxel must be administered in a vehicle of 50% alcohol/50% polyoxyethylated caster oil, which can lead to an enhanced risk of hypersensitivity reactions (dyspnea, hypotension, angioedema, and uticaria)... 

On the basis of an in vitro study using human liver sliees and human liver mierosomes it has been coneluded that the metabolism of paclitaxel is unlikely to be altered by cimetidine, dexamethasone or diphenhydramine, all of which are frequently given to prevent the hypersensitivity reactions associated with paclitaxel or its vehicle, Cremophor (see b, below). The UK manufacturers say that paclitaxel clearance in patients is not affected by cimetidine premedication, although some authors have advised caution when using cimetidine with docetaxel or paclitaxel since cimetidine is known to affect the cytochrome P450 isoenzyme CYP3A4, which is responsible, in part, for the metabolism of these taxanes. 

The Castells group treated 17 consecutive patients with hypersensitivity to taxanes using a standard 6-7 h desensitization protocol. The patients underwent a total of 77 rapid desensitizations to docetaxel or pachtexal. Seventy two of the procedures were tolerated without reactions, four patients responded with hypersensitivity reactions that were milder than their initial reactions, and these patients toleratedre-administration of infusions. Five patients rechallenged before desensitization experienced recurrent reactions even though they were given additional premedication, and the infusion rate was reduced. 

Up to 30 % of patients develop acute infusion reactions to taxanes. Acute hypersensitivity reactions are marked by urticaria, flushing, rashes, dyspnea, gastrointestinal symptoms, hypo- and hypertension, and back pain. 

In phase 1 studies, sagopilone has a similar adverse reactions profile to those of taxanes and ixabepilone neuropathy and neutropenia are the most commonly reported adverse events [16 ]. Motor neuropathy has not been reported so far, although in one phase I study, two patients reported symptoms of central ataxia [164=]. Diarrhea is less common with sagopilone than with ixabepilone and patupilone. Premedication is not routinely given with sagopilone and hypersensitivity reactions have not been reported so far. 

Paclitaxel Taxane (Diterpene) Breast, ovarian, head and neck, lung, bladder, etc. Inhibition mitotic cell division Acral erythema injection site reaction AGEP-Uke EM SJS Neutre nia hypersensitivity pn GI synptoms back pain Dys Incidence 10-16 % without premedication. Risks—atopy, bee sting allergy... 

Taxanes such as docetaxel and paclitaxel are mitotic inhibitors, disrupting microtubule function so adverse reactions, including hypersensitivity responses, to these drugs might be expected. 

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