Treatment of Paclitaxel-Related Neuropathy?

Harold J. Burstein, MD, PhD

Disclosures

November 09, 2000

Question

Is there any effective treatment for paclitaxel-induced sensory neuropathy?

D.J. Montgomery, MD

Response from Harold J. Burstein, MD, PhD

Peripheral neuropathy is a common side effect of paclitaxel therapy.[1] Typically, this is a "stocking-and-glove" type of peripheral neuropathy that may be associated with numbness, paresthesias, and loss of sensory function. A less common motor neuropathy has also been reported.[2] Mild symptoms (grade 1 or 2) are reported by many patients, especially with repetitive dosing. Up to two-thirds or more of treated patients may report some symptoms. Severe, disabling neuropathy is less common. Grade 3 or 4 peripheral neuropathy is reported in 5% to 10% of patients treated at 175 mg/m2 every 3 weeks,[3] and with greater frequency at higher treatment doses.[4] Weekly administration of "dose-dense" paclitaxel can also cause neurotoxicity, especially at doses in excess of 100 mg/m2 per week and with sustained treatment.[5] Patients with pre-existing neuropathy from diabetes, other medical conditions, or prior chemotherapy exposure are at greater risk for paclitaxel-related neuropathy.

There are no established treatments for paclitaxel-related neuropathy.[6] Cessation of therapy generally leads to symptom improvement over weeks to months. Most treatment protocols call for dose reduction of paclitaxel (typically, 25%) for mild neuropathy symptoms and interrupting paclitaxel therapy for more severe symptoms. If severe symptoms fail to resolve with temporary cessation of therapy, paclitaxel should be discontinued.

Recently, there has been interest in the use of the amino acid glutamine as a possible treatment for paclitaxel-related neuropathy. To my knowledge, based on a literature search using PUBMED and discussion with colleagues, there are no published data on the clinical efficacy of glutamine for this purpose in cancer patients. In an in vivo rat model, glutamine therapy has been shown to prevent paclitaxel-related neuropathy.[7] Anecdotal clinical evidence suggests that glutamine may ameliorate paclitaxel-related myalgias.[8] Glutamine is being prospectively evaluated as a treatment for paclitaxel-related neuropathy and paclitaxel-related arthralgias/myalgias at several cancer centers. The treatment dose in most human clinical trials is 10 g orally 3 times a day, starting the day of or the day after paclitaxel administration, for a duration of between 1 and 5 days. Glutamine is sold as a nutritional supplement, and most preparations are not subject to FDA approval. Some preparations may contain additional nutritional supplements or vitamins, including antioxidants. It is not known what effect, if any, these compounds might have on the clinical efficacy of paclitaxel.

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