Peripheral neuropathy paclitaxel

Paclitaxel Peripheral neuropathy (DLT), nausea/vomiting, alopecia, hypersensitivity reactions Use caution with any elevation in AST (SGOT). Give proper dosing for liver dysfunction. Premedicate dexamethasone, diphenhydramine, and cimetidine. 

Paclitaxel -natural taxane inhibits depolymerization of tubulin in mitotic spindle apparatus -bone marrow suppression -nausea and vomiting—mild -mucocutaneous effects (mucositis, stomatitis, diarrhea) -hypersensitivity reactions -peripheral neuropathy -myalgias, arthralgias -mild vesicant... 

Sissung, T. M., Mross, K., Steinberg, S. M., et al. (2006) Association of ABCBl genotypes with paclitaxel-mediated peripheral neuropathy and neutropenia. Eur. J. Cancer. 42, 2893-2896. 

Myelosuppression is the major side effect of paclitaxel. Alopecia is common, as is reversible dose-related peripheral neuropathy. Most patients have mild numbness and tingling of the fingers and toes beginning a few days after treatment. Mild muscle and joint aching also may begin 2 or 3 days after initiation of therapy. Nausea is usually mild or absent. Severe hypersensitivity reactions may occur. Cardiovascular side effects, consisting of mild hypotension and bradycardia, have been noted in up to 25% of patients. 

Paclitaxel Taxol Carcinoma of the breast, ovaries Kaposi sarcoma nonsmall cell lung cancer Blood disorders (anemia, leukopenia, neutropenia, thrombocytopenia] hypersensitivity reaction (skin rash/itching, shortness of breath] joint/muscle pain peripheral neuropathies Gl distress (nausea, vomiting, diarrhea]... 

Flatters, S. J., and Bennett, G. J. (2004). Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy. Pain 109, 150—161. 

The plant alkaloids (vincristine, vinblastine, vindesine and vinorelbine) and taxoids (paclitaxel, docetaxel) inhibit microtubule assembly and cause cell cycle arrest in mitosis. They particularly cause bone marrow depression, peripheral neuropathy (vincristine) and alopecia. Etoposide blocks the cell cycle before mitosis. 

The most common nervous system effect is peripheral neuropathy, although one patient developed tonic-clonic seizures whilst receiving paclitaxel and required treatment with benzodiazepines and barbiturates (14). Motor weakness has occasionally been reported (24). 

Peripheral neuropathy presents as numbness, burning, and tingling in a glove-and-stocking distribution. Symptoms usually begin 24-72 hours after treatment with paclitaxel, with a symmetrical distal loss of sensation. Most cases occur at doses over 200 mg/m and particularly after multiple courses (24—26). Mild to moderate sensory neuropathy has occurred in 52% of patients treated with doses of 175 mg/m, while only 36% experienced neuropathy at doses of at least 135 mg/m (17,24,28,29). At the lower dose of 135 mg/m, the effects are usually limited to a mild sensory neuropathy (17,29). 

Tricyclic antidepressants, in particular amitriptyline, and venlafaxine are helpful in relieving symptoms of paclitaxel-induced peripheral neuropathy (1,26,33,34). 

In 21 patients with advanced non-small cell lung cancer carboplatin had no effect on the pharmacokinetics of paclitaxel 135-200 mg/m as a 24-hour intravenous infusion (58). Peripheral neuropathy occurred in 13 of 37 patients treated with paclitaxel 175 mg/m and carboplatin (59). The authors concluded that clinically important neurotoxicity increases with every cycle of chemotherapy. The peripheral neuropathy mainly affected sensory fibers without involving motor nerves. The same paclitaxeP carboplatin chemotherapy in 28 women caused no signs of acute central neurotoxicity or neuropsychological deterioration however, 11 patients had a peripheral neuropathy (60). 

The concomitant or previous use of potentially neurotoxic drugs (for example paclitaxel, vinca alkaloids, or hexam-ethylmelamine) can increase the risk of peripheral neuropathy due to platinum compounds (68,69). 

Mielke S, Sparreboom A, Steinberg SM et al (2005) Association of paclitaxel pharmacokinetics with the development of peripheral neuropathy in patients with advanced cancer. Clin Cancer Res 11 4843M850... 

Argyriou AA, Chroni E, Koutras A et al (2006) Preventing paclitaxel-induced peripheral neuropathy a phase II trial of vitamin E supplementation. J Pain Symptom Manage 32 237-244... 

Baldwin RM, Owzar K, Zembutsu H et al (2012) A genome-wide association study identifies novel loci for paclitaxel-induced sensory peripheral neuropathy in CALGB 40101. Clin Cancer Res 18 5099-5109... 

Adverse effects of paclitaxel and docetaxel are similar, being hypersensitivity reactions, bone marrow suppression, peripheral neuropathy, hair loss and cardiac arrhythmias. 

Toxicity Paclitaxel causes neutropenia, thrombocytopenia, a high incidence of peripheral neuropathy, and possible hypersensitivity reactions during infusion. Docetaxel causes neurotoxicity and bone marrow depression. 

Paclitaxel Bone marrow suppression, peripheral neuropathy, alopecia... 

Certain drugs, such as paclitaxel and vincristine, could cause peripheral neuropathy [92]. Similarly, anthracyclines are known for rare but serious cardiotoxicity [93, 94]. 

Siau C, Xiao W, Bennett GJ. Paclitaxel- and vincristine-evoked painful peripheral neuropathies loss of epidermal innervation and activation of Langerhans cells. Exp Neurol 2006 201 507-514. 

The rate of infusion also has an effect on the adverse reactions profile of paclitaxel. Shorter infusions are associated with less myelotoxicity but more acute hypersensitivity and peripheral neuropathy [22 ]. 

Nervous system Neurotoxicity associated with paclitaxel b dose-related, cumulative, and characterized principally by a sensory peripheral neuropathy, although motor weakness has occasionally been reported [4H]. In patienb treated with paclitaxel 135... 

Peripheral neuropathy presents as numbness, burning, and tingling in a glove-and-stocking distribution. Symptoms usually begin 24-72 hours after treatment with paclitaxel, with a symmetrical distal loss of sensation. Once treatment is stopped, the symptoms generally subside within several weeks to months [34 =]. 

Previous exposure to potentially neurotoxic chemotherapeutic agents, such as platinum compounds and vinca alkaloids, does not appear to increase the risk of neurotoxicity with paclitaxel [5 ]. However, patients with co-existing medical illnesses associated with peripheral neuropathy, such as diabetes mellitus and alcohol abuse, may be more likely to develop a peripheral neuropathy. 

A pre-existing neuropathy as a result of prior therapy is not a contraindication to paclitaxel, but in severe cases of peripheral neuropathy a dosage reduction of 20% is recommended for subsequent courses. 

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