Genetic Marker Predicts Taxane-Induced Neuropathy

[Hopeful]

Elsevier Global Medical News. 2011 May 20, J Smith

EXPERT COMMENTARY

Isabel Cunningham, MD, Associate Editor

Optimism for a Genetic Predictor of Taxane Neurotoxicity

The first potential biomarker useful in predicting taxane neurotoxicity may be near. A marker in the RWDD3 gene was identified in an ECOG study of 2204 patients with early-stage breast cancer after 12 weeks of weekly paclitaxel. Results are to be presented at ASCO. Divided into 3 genetic subgroups, neuropathy occurred in 27%, 40%, and 60% of patients at 15 months. A subset analysis is underway for African American patients, who had a twofold increase in neuropathy.


News Article

Researchers have identified a genetic biomarker that can predict a patient's likelihood of experiencing taxane-induced peripheral neuropathy.

Older people and blacks, the same study found, are at elevated risk of developing neuropathy, which affects up to a third of people receiving chemotherapy with taxane drugs such as paclitaxel.

The marker in the RWDD3 gene, if developed into a blood test, would allow clinicians to identify patients vulnerable to peripheral neuropathy, which is characterized by a pain and numbness in fingers and toes and can keep patients from receiving the intended amount of their therapy, complicating treatment.

The findings, released at a press briefing in advance of the American Society of Clinical Oncology's annual meeting, came from a large genome-wide association study of 2,204 early-stage breast cancer patients enrolled in a clinical trial that used weekly paclitaxel for 12 weeks in all arms. This marked the first time a genetic predictive biomarker has been reported for taxane-induced neuropathy.

For their research, Dr. Bryan P. Schneider of the Simon Cancer Center at Indiana University, Indianapolis, and his colleagues, looked for variations in DNA called single nucleotide polymorphisms (SNPs) in each patient. During the study and follow-up period, 613 of the patients reported experiencing grade 2-4 neuropathy.

By looking at more than 1.2 million SNPs in each patient, Dr. Schneider and his colleagues were able to identify genetic subgroups most likely to develop neuropathy. "Those who carried two normal nucleotides in a specific regulatory gene had a 27% chance of experiencing neuropathy," the investigators wrote in their abstract. "But those who carried one normal nucleotide and one SNP had a 40% chance and those who carried two SNPs had a 60% chance."

Dr. Schneider and his colleagues also found that older patients and blacks were much more likely to have peripheral neuropathy. The likelihood of neuropathy increased 12.9% with every decade of age. Blacks saw a twofold increase in the likelihood of developing neuropathy.

Dr. Schneider and his colleagues' data came from a study funded by the Eastern Cooperative Oncology Group under the National Cancer Institute. Dr. Schneider disclosed a consulting relationship with Genentech, and several of his coauthors reported consulting relationships with, or having received research funding or honoraria from Genentech.

Hopeful