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Docetaxel-Induced Peripheral Neuropathy in Breast Cancer Survivors

It is well known that chemotherapy-induced symptoms, including peripheral neuropathy, often lead to the reduction or premature discontinuation of drug dosages in a large proportion of patients. This can mean that patients receive significantly less chemotherapy. The taxanes, paclitaxel and docetaxel, are one class of chemotherapeutic drugs with this effect.

Recently, Lise Eckhoff and her colleagues have conducted research on docetaxel-induced neuropathy among 1,725 Danish women with early-stage breast cancer. This study confirmed that those with chemotherapy-induced PN received significantly lower cumulative doses of chemotherapy. In more recent research, Eckhoff et al. have investigated the effect of genetic variants (GSTP1 and ABCB1) on the development of docetaxel-induced PN in a case-control study of 150 women with early-stage breast cancer. They found the GSTP1 Ala114Val polymorphism to be associated with doxetaxel-induced PN, which supports the theory that oxidative stress is involved. The results, if confirmed, may have significant implications for more accurate assessment of risk for this adverse event.

Eckhoff and colleagues have also investigated the persistence of docetaxel-induced neuropathy and its impact on quality of life among more than 1,000 breast cancer survivors, who were surveyed by questionnaire. Patterns of PN varied among these women. About 23% of the women reported PN of grade 2 to 4 upon completion of treatment. In some, it persisted for 1 to 3 years, while in others it regressed to a milder form. About 10% of women who did not have PN upon completing treatment developed PN later. Overall, about 15% of these breast cancer survivors developed docetaxel-induced PN 1 to 3 years after treatment. Risk factors associated with post-treatment PN were older age (> 55), a high grade of PN during treatment, persistent muscle and joint pain, stomatitis, and fatigue. Persistent PN was associated with functional impairment and significantly lower health-related quality of life.

Painful peripheral neuropathy remains a challenging complication of cancer chemotherapy. The work of Eckhoff et al. is important to the improvement of risk prediction and better management of neurotoxicity.

Related Publications
Eckhoff L, Knoop A, Jensen M, Ewertz M. Persistence of docetaxel-induced neuropathy and impact on quality of life among breast cancer survivors. Eur J Cancer. 2015 Feb;51(3):292-300.

Eckhoff L, Feddersen S, Knoop AS, Ewertz M, Bergmann TK. Docetaxel-induced neuropathy: A pharmacogenetic case-control study of 150 women with early-stage breast cancer. Acta Oncol. 2014 Nov 10:1-8.

Eckhoff L, Knoop AS, Jensen MB, Ejlertsen B, Ewertz M. Risk of docetaxel-induced peripheral neuropathy among 1,725 Danish patients with early stage breast cancer. Breast Cancer Res Treat 2013 Nov;142(1):109-18.