Comorbidities and Risk of Chemotherapy-Induced Peripheral Neuropathy Among Participants 65 Years or Older in Southwest Oncology Group Clinical Trials

Abstract

Listen to the podcast by Dr Paice at www.jco.org/podcastsNeuropathy is a debilitating toxicity associated with various chemotherapy agents. We evaluated the association between common comorbid conditions and the development of peripheral neuropathy in patients treated with taxane-based chemotherapy. MethodsWe examined the Southwest Oncology Group database to identify phase II and III trials that included taxane therapy from 1999 to 2011. We linked the Southwest Oncology Group clinical records to Medicare claims data according to Social Security number, sex, and date of birth. The following disease conditions potentially associated with peripheral neuropathy were evaluated: diabetes, hypothyroidism, hypercholesterolemia, hypertension, varicella zoster, peripheral vascular disease, and autoimmune diseases. Multivariate logistic regression was used to model the odds of experiencing grade 2 to 4 neuropathy. ResultsA total of 1,401 patients from 23 studies were included in the analysis. Patients receiving paclitaxel were more likely to experience grade 2 to 4 neuropathy compared with docetaxel (25% v 12%, respectively; OR, 2.20; 95% CI, 1.52 to 3.18; P , .001). The inclusion of a platinum agent was also associated with greater neuropathy (OR, 1.68; 95% CI, 1.18 to 2.40; P = .004). For each increase in age of 1 year, the odds of neuropathy increased 4% (P = .006). Patients with complications from diabetes had more than twice the odds of having neuropathy (OR, 2.13; 95% CI, 1.31 to 3.46; P = .002) compared with patients with no diabetes. In contrast, patients with autoimmune disease were half as likely to experience neuropathy (OR, 0.49; 95% CI, 0.24 to 1.02; P = .06). The other conditions were not associated with neuropathy. ConclusionWe found that in addition to drug-related factors, age and history of diabetes were independent predictors of the development of chemotherapy-induced peripheral neuropathy. Interestingly, we also observed that a history of autoimmune disease was associated with reduced odds of neuropathy. Patients with diabetic complications may choose to avoid paclitaxel or taxane plus platinum combination therapies if other efficacious options exist.

Clinical and Genome-Wide Analysis of Cisplatin-Induced Peripheral Neuropathy in Survivors of Adult-Onset Cancer

“…The relationship with age is consistent with several previous reports of taxane-induced neuropathy, including ECOG 5103 (4, 8, 36). In contrast, a number of studies of oxaliplatin-treated patients did not find an association with age (6, 7).…”

“…Unlike taxane-related CIPN, which can be reversible (2), cisplatin-induced peripheral neuropathy (CisIPN) can be cumulative and progressive and cause long-term effects on overall quality of life (QoL) and physical function (3). Studies have suggested that age, race, diabetes and obesity may be risk factors for CIPN (4, 5), but results have been conflicting (6–11). …”

Prevention and Management of Chemotherapy-Induced Polyneuropathy

“…Strong independent individual risk factors for developing CIPN are diabetes mellitus, age [5], and concurrent exposure to other neurotoxic agents as well as pre-existing neuropathy. Furthermore, alcohol abuse, metabolic diseases such as renal insufficiency, hypothyroidism, vitamin deficiency (e.g., B 1 , B 6 , B 12 ), and pre-existing hereditary neuropathies like CMT1A are considered to be risk factors [6].…”

Partial Protection of Paclitaxel-induced Neurotoxicity by Antioxidants

“…thrombocytopenia, neutropenia and fatigue (4) and anorexia and constipation (5). Patients who received platinum treatment with a taxane were more likely to experience grade 2 to 4 neuropathy (6). Paclitaxel has been reported to induce oxidative stress in liver (slight, but no significant decrease in glutathione in liver) (7).…”