The Effect of Diabetes on Oxaliplatin-Induced Peripheral Neuropathy
ABSTRACT INTRODUCTION: Chemotherapy-induced neurotoxicity is a significant source of morbidity for cancer patients. This study aimed to assess the relationship between preexisting diabetes and clinically significant (National Cancer Institute Common Toxicity Criteria grades 2 and 3) OXIPN; between diabetes, and the cumulative dose at onset of OXIPN; and between other preexisting medical conditions and the development of OXIPN. MATERIALS AND METHODS: We reviewed medical records of all patients with stage II-IV colon cancer treated in the Albert Einstein Cancer Center, Philadelphia, with oxaliplatin from 2005 to 2009. Exclusion criteria included preexisting neuropathy, previous neurotoxic chemotherapy exposure, and incomplete medical records. The NCI Common Toxicity Criteria was used to grade sensory neuropathy. Univariate analysis was used to estimate odds ratios and confidence limits for prevalence of OXIPN in patients with and without diabetes. The mean level and cumulative doses were compared using the t test. RESULTS: Sixty-two patients met the study criteria; 23 oxaliplatin-treated patients were excluded. The crude incidence of any OXIPN was 65%. There was no relationship found between development of OXIPN and the presence of diabetes, smoking, hypertension, or statin use. However, the mean cumulative dose of oxaliplatin was significantly lower for patients with diabetes who developed neuropathy, compared with those without diabetes (388 vs. 610 mg/m(2); P = .021). CONCLUSION: Although the presence of diabetes did not appear to affect the severity of OXIPN, patients with diabetes developed OXIPN at a lower cumulative dose of oxaliplatin (P < .05). The results may have implications for treatment of patients with diabetes and colon cancer.
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ABSTRACT: Prolonged neurotoxicity after systemic chemotherapy has the potential to impact on quality of life. We explored the frequency of persistent peripheral neuropathy in patients who received oxaliplatin for colorectal cancer at two local centres. Questionnaires were sent to patients who completed treatment with oxaliplatin for colorectal cancer at least 20 months prior to entering the study. Neuropathy questions were adapted from the FACT/GOG-Ntx (V.4) questionnaire. Of the 56 eligible patients, 27 returned the questionnaire. Twenty-five patients (93 %) experienced neuropathic symptoms during their treatment; 11 had grade-2, and two had grade-3 symptoms. At the time of completing the questionnaire, 17 patients (63.0 %; 95%CI 43.9-79.4 %) were still symptomatic with 12 patients (44.4 %; 95%CI 26.8-63.3) having grade-2 or grade-3 symptoms and three patients (11.1 %; 95%CI 2.9-27.3) having grade-3 neuropathic symptoms. Participants who received more than 900 mg/m(2) oxaliplatin had a significantly higher risk of persistent grade-2 or grade-3 neuropathy (p = 0.031, RR = 8.3 95%CI = 1.2-57.4). There was a trend toward increased risk of persistent neuropathy of any grade among participants with a history of regular alcohol use (p = 0.051; RR = 1.7 95%CI 1.0-2.8). Persistent oxaliplatin-induced neuropathy is not as uncommon as previously suggested, and the rate of grade-2 and grade-3 symptoms could be considerably higher than previous reports.Supportive Care in Cancer 10/2013; 22(2). DOI:10.1007/s00520-013-2004-3 · 2.09 Impact Factor
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ABSTRACT: Chemotherapy-induced peripheral neuropathy is frequently a dose-limiting factor in cancer treatment and may cause pain and irreversible function loss in cancer survivors. We tested whether alpha-lipoic acid (ALA) could decrease the severity of peripheral neuropathy symptoms in patients undergoing platinum-based chemotherapy. Cancer patients 18 years or older were randomly selected to receive either 600 mg ALA or a placebo three times a day orally for 24 weeks while receiving chemotherapy regimens including cisplatin or oxaliplatin. Neuropathy was measured by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) scale and the NCI Common Toxicity Criteria for Adverse Events neurotoxicity grades. Results from timed functional tests and the Brief Pain Inventory (BPI) were secondary endpoints. Seventy of 243 (29 %) patients completed the study (24 weeks). Both the ALA and the placebo arms had a comparable drop-out rate. No statistically significant differences were found between the ALA and the placebo groups for FACT/GOG-Ntx scores, BPI scores, and patients' functional outcomes. This strategy of oral ALA administration was ineffective at preventing neurotoxicity caused by oxaliplatin or cisplatin. High attrition rates due to poor patient compliance and manner of dosage administration in this trial demonstrated a lack of feasibility for this intervention. Future studies to explore ALA as a neuroprotective agent should take heed of the barriers confronted in this study.Supportive Care in Cancer 12/2013; 22(5). DOI:10.1007/s00520-013-2075-1 · 2.09 Impact Factor
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ABSTRACT: Purpose of review This review focuses on the newest data on mechanistic aspects of chemotherapy-induced peripheral neuropathy (CIPN), its assessment and the current status of neuroprotection and treatment options. Recent findings Several anticancer drugs are associated with CIPN. Rodent models showed that axons, dorsal root ganglia and terminal trees are affected, whereas myelin remains unaffected. Oxidative stress and mitochondrial damage, as well as the role of nerve growth factor, have been highlighted in CIPN. Candidate genes, single nucleotide polymorphisms, were correlated with a higher incidence of CIPN in patients receiving a combination of chemotherapies. CIPN assessment mainly relies on patient-oriented questionnaires, nevertheless an international effort is ongoing to access reliable and objective means to assess small and large fiber impairment. To date, dose modification is the most effective strategy to prevent CIPN, whereas duloxetine is recommended for patients with painful CIPN. Summary CIPN is a common, potentially severe and dose-limiting adverse effect of cancer treatment. Chemotherapies mainly target axons, dorsal root ganglia and terminal trees of intraepidermal nerve fibers. A quick and noninvasive method allowing the assessment of CIPN should be developed, although no treatment prevents CIPN or improves its long-term course. Furthermore, symptomatic therapy is often largely ineffective in reducing CIPN symptoms.Current Opinion in Oncology 09/2014; 26(6). DOI:10.1097/CCO.0000000000000139 · 3.76 Impact Factor