Longitudinal study of inflammatory, behavioral, clinical, and psychosocial risk factors for chemotherapy-induced peripheral neuropathy

Abstract

Purpose. 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. Methods. 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 six 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. Results. 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. Conclusions. 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. Trial Registration . NCT00924651

Mechanisms, Mediators, and Moderators of the Effects of Exercise on Chemotherapy-Induced Peripheral Neuropathy

“…Proinflammatory cytokine upregulation and inflammatory cascade activation are implicated in the development of CIPN [ 31 , 32 ]. Because exercise has been shown to have anti-inflammatory effects, it may have the potential to ameliorate CIPN via anti-inflammatory cascades.…”

“…Current understanding of the psychosocial mechanisms behind the impact of exercise on CIPN is limited, and is primarily based on the relationship between exercise and mental health (e.g., mood, well-being, anxiety, and depression), which is related to CIPN [ 32 , 59 ]. Despite the fact that the psychosocial benefits of exercise are well-established, we believe it is prudent to include this discussion to (1) emphasize the importance of these mechanisms in the specific context of CIPN, (2) bridge cross-disciplinary knowledge gaps across CIPN research, and (3) promote future research in this area.…”

“…CIPN symptoms can limit activities of daily living and contribute to fatigue, anxiety, and depression [ 32 , 59 , 60 ]. Exercise may treat CIPN through known mechanisms for improving mood and reducing distress.…”

“…For example, moderate-intensity aerobic exercise (e.g., walking) can offer time away from stress, expose patients to greenspace, and provide opportunity for socialization [ 61 , 62 ]. Meta-analytical studies suggest that this kind of exercise can have a positive anxiolytic and depression-reducing effect, potentially involving neurological mechanisms such as the interoceptive brain system [ 32 , 63 ]. In addition, aerobic, resistance, and anaerobic exercise have shown efficacy in improving cancer-related fatigue during and after primary treatment, possibly by way of improving oxygen circulation in the body and increasing energy efficiency [ 32 , 64 ].…”

“…One commonly suggested neurophysiological mediator of exercise and CIPN is inflammation. Because inflammation has been implicated in CIPN [ 31 , 32 ] and exercise has been shown to have anti-inflammatory effects [ 33 , 36 ], exercise is a promising treatment for inflammation-related CIPN. If a patient is known to have high levels of inflammation, then it will likely be beneficial to prescribe an exercise program that is targeted towards anti-inflammation.…”