Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of taxane and platinum chemotherapy for breast cancer. Clinicians cannot accurately predict CIPN severity partly because its pathophysiology is poorly… Click to show full abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of taxane and platinum chemotherapy for breast cancer. Clinicians cannot accurately predict CIPN severity partly because its pathophysiology is poorly understood. Although inflammation may play a role in CIPN, there are limited human studies. Here, we identified the strongest predictors of CIPN using variables measured before taxane- or platinum-based chemotherapy, including serum inflammatory markers. 116 sedentary women with breast cancer (mean age 55 years) rated (1) numbness and tingling and (2) hot/coldness in hands/feet on 0–10 scales before and after 6 weeks of taxane- or platinum-based chemotherapy. A sub-study was added to collect cytokine data in the final 55 patients. We examined all linear models to predict CIPN severity at 6 weeks using pre-chemotherapy assessments of inflammatory, behavioral, clinical, and psychosocial factors. The final model was selected via goodness of fit. The strongest pre-chemotherapy predictors of numbness and tingling were worse fatigue/anxiety/depression (explaining 27% of variance), older age (9%), and baseline neuropathy (5%). The strongest predictors of hot/coldness in hands/feet were worse baseline neuropathy (11%) and fatigue/anxiety/depression (6%). Inflammation was a risk for CIPN, per more pro-inflammatory IFN-γ (12%) and IL-1β (6%) and less anti-inflammatory IL-10 (6%) predicting numbness/tingling and more IFN-γ (17%) and less IL-10 (9%) predicting hot/coldness in hands/feet. The strongest pre-chemotherapy predictors of CIPN included worse fatigue/anxiety/depression and baseline neuropathy. A pro-inflammatory state also predicted CIPN. Because this is an exploratory study, these results suggest specific outcomes (e.g., IL-1β) and effect size estimates for designing replication and extension studies. Clinical trial registration: NCT00924651.
               
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