Docetaxel syndrome

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... 

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)... 

Skin and subcutaneous tissue disorders Reversible cutaneous reactions have been observed and are generally mild to moderate. Reactions are characterised by a rash including localised eruptions mainly on the feet and hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently associated with pruritus. Eruptions generally occur within one week after the docetaxel infusion. Severe nail disorders are characterised by hypo- or hyperpigmentation and sometimes pain and onycholysis. 

Both paditaxel and docetaxel may result in anaphylactoid or severe hypersensitivity reactions manifested by dyspnea, bronchospasm, angioedema, hypotension (occasionally HTN), and urticarial skin reactions. The reaction may be due to the active drug itself or to the vehicle (Cremophor or polysorbate 80). Additionally, patients receiving docetaxel may experience serious or life-threatening fluid retention. This syndrome is characterized by poorly tolerated peripheral or generalized edema, pleural effusion, dyspnea, ascites, and cardiac tamponade. 

Dexamethasone 8 mg orally twice daily for 3 days (starting 1 day prior to docetaxel) is recommended to lower risk of fluid retention syndrome shorter dexamethasone regimens used for weekly docetaxel dosing Requires dose reduction for liver dysfunction (elevated total bilirubin, elevated transaminases and/or alkaline phosphatase)... 

A recent multi-institution survey in Japan drew attention to an important effect of histamine H2 antagonists on docetaxel-induced skin toxicity. Analyses revealed that administration of H2 blockers was associated with a significantly higher incidence of acral erythema (hand-foot syndrome palmar-plantar erythrodysesthesia compare with hand-foot skin reaction. Sects. 13.3.2 and 13.3.3 and see Fig. 13.1) and facial erythema. Steroids and H2 blockers affect the metabolism of docetaxel by cytochrome P45o3A4 (CYP3A4), but dexamethasone dosage did not change the incidence of hand-foot syndrome or facial edema. 

Cardiovascular Heart failure (New York Heart Association classes II-IV) has been observed in patients receiving trastuzumab, alone or in combination with paclitaxel or docetaxel, particularly after chemotherapy containing an anthracycline (doxorubicin or epirubicin) [303, 304, 305, 306. It can be moderate or severe and can be fatal. The results of many randomized trials have shown that the degree of cardiotoxicity is generally acceptable the incidence of cardiac damage caused by trastuzumab was 0.4-4.1% [307 ]. Older age, lower left ventricular ejection fraction, and antihypertensive medications are associated with an increased risk of cardiac dysfunction in patients receiving trastuzumab [308 "]. The cardiac dysfunction associated with trastuzumab is usually reversible on withdrawal and standard medical therapy [309 ]. In one case, trastuzumab-associated cardiomyopathy presented with complete left bundle-branch block mimicking acute coronary syndrome [310" ]. 

Palmar-plantar erythrodysesthesia syndrome (commonly called hand-foot syndrome) has been reported to be associated with docetaxel, although various patterns of spread, from solitary erythematous plaques to widespread involvement of the trunk, have been observed [139, 140 ]. 

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