Genetic Biomarker Predictive of Peripheral Neuropathy in Patients Receiving Docetaxel for Prostate Cancer
Docetaxel-induced neuropathy may be predicted by single nucleotide polymorphisms in VAC14. Docetaxel is a taxane commonly used to treat cancers of the breast, ovary, or prostate; however, significant side effects limit their use.1
A common side effect of taxanes is peripheral neuropathy, which can manifest as weakness, numbness, and pain usually in the hands or feet and occasionally in other areas of the body. Peripheral neuropathy can limit the use of an otherwise effective cancer treatment.
Researchers in this study analyzed the DNA of men with castrate-resistant metastatic prostate cancer who had participated in a randomized phase 3 clinical trial that included docetaxel in the treatment regimen. Of 623 patients with prostate cancer from the study, 50 (8.1%) experienced debilitating peripheral neuropathy.
When the researchers examined the patients' DNA for genetic variations known as single nucleotide polymorphisms (SNPs) to find those associated with peripheral neuropathy, they found a variation in the VAC14 gene. It was highly associated with the incidence of docetaxel-induced peripheral neuropathy.
"The genetic variant of VAC14 identified in this study could be useful for understanding the mechanism of docetaxel-induced neuropathy and may be informative for avoiding docetaxel treatment in patients at elevated neuropathy risk," said Howard McLeod, PharmD, medical director of the DeBartolo Family Personalized Medicine Institute at Moffitt Cancer Center in Tampa, Florida. "This also offers new drug development strategies to improve the outcomes for cancer patients."
1. Hertz DL, Owzar K, Lessans S. Pharmacogenetic discovery in CALGB (Alliance) 90401 and mechanistic validation of a VAC14 polymorphism that increases risk of docetaxel-induced neuropathy [published online ahead of print May 3, 2016]. Clin Cancer Res. doi:10.1158/1078-0432.CCR-15-2823.