As an oncologist who frequently avoids taxanes, largely due to concerns about neuropathy, Steven Vogl, MD, of the Bronx, New York, was asked to comment on the study. He observed that while the Indiana University study has no immediate applicability, it is “a good first look.”

“I typically don’t use taxanes for patients at low risk for recurrence because it’s been difficult to consistently show they add much,” he told The ASCO Post. “But if I knew my low-risk patient had little risk of developing neuropathy, I might be more willing to give a taxane.”

The Schneider study is “the Taxol franchise” of the emerging business of “SNP neurotoxicity searches,” Dr. Vogl quipped. A similar study recently identified SNPs associated with chemotherapy-induced neuropathy in multiple myeloma,^1,2 he noted. Specifically, ATP-binding cassette gene family SNPs were linked to thalidomide (Thalomid)-induced neuropathy, whereas the SNPs involved in vincristine-induced neuropathy were in different genes. The discrepancies point to different pathogenic mechanisms for nerve damage from the two agents, the authors suggested.

Interpreting the Data

In the current study, the findings of two relevant SNPs among 1.2 million possibilities might be due to chance, or the SNPs could be artifacts (linked by heredity to the real genetic causes), according to Dr. Vogl. “But if they were the same as those found in these myeloma studies, that would be interesting,” he suggested. Ideally, the biomarkers should discriminate those who develop mild neuropathy from those who develop severe neuropathy. “While transient grade 2 neuropathy can be miserable, it’s more important to identify patients whose neuropathy does not resolve,” he noted.

A genetic risk profile would help justify the withholding of taxanes in patients at low risk for recurrence but high risk for neuropathy, and would support the decision to use a different drug or a toxicity-modifying agent or schedule in patients at risk for both recurrence and neuropathy, he said. ■

Financial Disclosure: Dr. Vogl reported no potential conflicts of interest.

References

1. Johnson DC, Corthals SL, Walter BA, et al: Genetic factors underlying the risk of thalidomide-related neuropathy in patients with multiple myeloma. J Clin Oncol 29:797-804, 2011.

2. Becker P: Genetic Predisposition for Chemotherapy-Induced Neuropathy in Multiple Myeloma. J Clin Oncol 29:783-786, 2011.