Inflammatory and clinical risk factors for chemotherapy-induced peripheral neuropathy (CIPN): A nationwide longitudinal study in 143 cancer patients during chemotherapy.

Abstract

12099 Background: CIPN is a common dose-limiting side effect of taxane and platinum chemotherapy. It is difficult for clinicians to predict who will experience CIPN before initiating chemotherapy, partly because the etiology of CIPN is poorly understood. Specifically, although inflammation putatively plays a role in CIPN, there is limited evidence of the role of inflammation in CIPN in humans. Here, we identified the strongest predictors of CIPN using variables measured before taxane or platinum chemotherapy, including serum inflammation. Methods: 143 sedentary patients with cancer (81% breast, 7% colon, 5% lung; 7% other; mean age 56 years) receiving taxane or platinum chemotherapy rated the severity of (a) numbness and tingling, and (b) hot/coldness in hands/feet on 0-10 point scales before and after their first 6 weeks of chemotherapy. Linear regression models were fit to predict CIPN symptom severity at 6 weeks using variables related to inflammation (serum IL-1β, IL-6, IL-8, IL-10, IFN-γ, sTNFR1; 69 patients who gave blood), clinical factors (cancer stage, baseline neuropathy, fatigue, anxiety, depression, using diabetes medications), behavior (daily pedometer steps), and demographics (age, race) measured before chemotherapy. The final model was identified by the smallest AIC goodness of fit. Results: The strongest pre-chemotherapy predictors of numbness and tingling after 6 weeks of taxane and/or platinum chemotherapy were worse patient-reported fatigue/anxiety/depression (explaining 25% of variance), platinum chemotherapy (7%), and older age (5%). The strongest predictors of hot/coldness in hands/feet included worse baseline neuropathy (13%), platinum chemotherapy (8%), and fatigue/anxiety/depression (6%). In the 69 patients with serum data, a more pro-inflammatory state was a risk factor for CIPN as higher levels of pro-inflammatory IL-1β (7%) predicted numbness/tingling, and lower levels of anti-inflammatory IL-10 (7%) predicted hot/coldness in hands/feet. Conclusions: The strongest pre-chemotherapy predictors of CIPN included worse fatigue/anxiety/depression and platinum chemotherapy in this sedentary population of cancer patients (mostly breast). A pro-inflammatory state before chemotherapy may also increase risk for CIPN, suggesting that inflammation may underlie the etiology of CIPN in humans. Clinicians should consider assessing these factors to inform the patient’s risk for CIPN. Funding: NCI UG1CA189961, NCI K07 K07CA221931, T32CA102618. Clinical trial information: NCT00924651 .