RISK FACTORS FOR CHEMOTHERAPY INDUCED NEUROPATHY

NEW YORK (Reuters Health) - In cancer patients, age and a history of diabetes are among factors associated with chemotherapy-induced peripheral neuropathy (CIPN), according to researchers.

As Dr. Dawn L. Hershman told Reuters Health by email, "Since we don't have any way at this point to prevent CIPN, knowing which patients may be at greatest risk for developing CIPN may help us personalize our treatments to avoid agents or combinations of agents that are associated with increased risk when other options exist."

In a June 20 online paper in the Journal of Clinical Oncology, Dr. Hershman, of Columbia University, New York, and colleagues note that to identify risk factors, they examined data from 23 phase 2 and 3 clinical studies involving cancer therapy.

The number of patients per study ranged from 11 to 408 and, in all, more than 1,400 patients treated with taxane-based chemotherapy were included in the analysis. Their mean age was around 73 years.

Patients receiving paclitaxel were significantly more likely to experience grade 2 to 4 neuropathy compared to those on docetaxel (odds ratio 2.20). The inclusion of a platinum agent was also associated with greater neuropathy (OR 1.68). For each increase in age of one year, the odds of neuropathy increased by 4%.

The most common comorbid disease conditions were hypertension (68%), hypercholesterolemia (48%), and diabetes (26%).

Compared to patients without diabetes, those with complications from the disease had more than twice the odds of having neuropathy (OR 2.13). However, patients with autoimmune disease were half as likely to experience grade 2 to 4 neuropathy (OR 0.49) and one-third as likely to experience grade 3 to 4 neuropathy (OR 0.32).

There was no evidence that other conditions including hypothyroidism, peripheral vascular disease, and varicella zoster were associated with neuropathy.

The researchers conclude, "Future studies should be performed to understand the role of the immune system and cytokine activation in the development and prevention of CIPN."

"In the meantime," they point out, "patients with diabetic complications should consider avoiding paclitaxel or taxane plus platinum combination therapies, if other options exist."

Commenting on the findings by email, Dr. Bryan P. Schneider of Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, told Reuters Health, "This is an interesting addition to the medical literature by a group of investigators with a strong reputation in the field."

Among the most important findings are "confirmation that paclitaxel causes more neuropathy compared with the other commonly used taxane, docetaxel. It also helps to confirm and quantify the incremental increased risk with the addition of platinum agents (which are commonly used with taxanes)."

The analysis also provides additional support to the idea "that older age and diabetes are important medical comorbidities that contribute to an increased risk." Thus, he added, "great caution should be taken or consideration of alternative therapeutics when appropriate options exist should be made when administering drugs to these populations of patients."

"This analysis," Dr. Schneider concluded, "provides novel insight into the potential protective effect of having an autoimmune condition. This finding might help experts understand more about the underlying mechanism of neuropathy and why it happens (or doesn't happen) to some patients. This type of insight can stimulate ideas for designing novel drugs to treat or prevent the neuropathy."

The National Cancer Institute, the American Society of Clinical Oncology, and the Breast Cancer Research Foundation supported this research. One coauthor reported research funding from Genentech.

SOURCE: http://bit.ly/290j7av

J Clin Oncol 2016.