A new study has identified the first genetic biomarkers for taxane-induced peripheral neuropathy, a potentially severe complication of taxane chemotherapy that affects nerves in about one-third of patients with cancer receiving such treatment.

The finding may eventually lead to a simple blood test to determine whether a patient is at high risk for neuropathy.

"If these findings can be replicated, this may allow physicians to know prior to recommending therapy whether the patient is at an inordinate risk for developing taxane-induced neuropathy," said Bryan P. Schneider, MD, lead author and a physician/researcher at the Indiana University Melvin and Bren Simon Cancer Center and Associate Director for the Indiana Institute for Personalized Medicine.

"This may allow for better counseling, use of alternative drugs or schedules, or omission of taxanes in the appropriate settings. These genetic findings might also provide insight into the mechanism of this side
effect and help develop drugs to prevent this toxicity altogether."

Such damage to the nerves can cause pain and numbness and limit the dose of chemotherapy a patient can receive. While only a few factors seem to predict which patients are likely to get peripheral neuropathy, including a history of diabetes and advanced age, genetic variations may explain why some patients are more sensitive to taxanes.

The authors conducted a genome wide association study on 2,204 patients enrolled in an Eastern Cooperative Oncology Group clinical trial (E5103) in which all patients received taxane-based chemotherapy. The study looked for variations in DNA called single nucleotide polymorphisms, or SNPs, evaluating more than 1.2 million SNPs in each patient. With a median follow-up of 15 months, the study identified genetic subgroups that were markedly more likely to develop peripheral neuropathy.

Those who carried two normal nucleotides in a specific regulatory gene had a 27 percent chance of experiencing neuropathy. But those who carried one normal nucleotide and one SNP had a 40 percent chance and those who carried two SNPs had a 60 percent chance. The study also found that older patients and African Americans were much more likely to have peripheral neuropathy, and further analysis of SNPs in these groups is underway.

The authors plan to continue their work in additional trials to validate these findings and to determine whether a different type or schedule of taxane therapy would result in less neuropathy in the more susceptible genetic groups. The authors also are collaborating with neurobiologists to understand why these genetic variations might make the nerves more sensitive to these drugs.


Source: ASCO

ASCO 2011 Abstract 1000: Genetic associations with taxane-induced neuropathy by genome wide association study (GWAS) in E5103. Authors: B. P. Schneider, L. Li, K. Miller, D. Flockhart, M. Radovich, B. A. Hancock, N. Kassem, T. Foroud, D. L. Koller, S. S.
Badve, Z. Li, A. H. Partridge, A. M. O'Neill, J. A. Sparano, C. T. Dang, D. W. Northfelt, M. L. Smith, E. Railey, G. W. Sledge