A Prospective Study of Chronic Oxaliplatin-Induced Neuropathy in Patients with Colon Cancer: Long-Term Outcomes and Predictors of Severe Oxaliplatin-Induced Neuropathy

Abstract

Background and PurposeThe objective of this study was to determine the incidence and long-term outcomes of oxaliplatin-induced peripheral neuropathy (OIPN), as well as predictors of its severe form.MethodsSixty-nine patients who were taking oxaliplatin for colon cancer were prospectively followed prior to starting chemotherapy and after 4, 8, and 12 cycles of chemotherapy. Thirty-six patients completed the follow-up at 1 year after the end of chemotherapy. The patients were assessed using clinical assessment scales and nerve conduction studies (NCS) at each follow-up visit.ResultsBy applying the National Cancer Institute Common Toxicity criteria, OIPN was classified as grade 1 in 30 (44%) patients, grade 2 in 25 (36%), and grade 3 in 10 (14%) at the completion of therapy. At 1 year after the treatment, OIPN of grades 1, 2, and 3 was found in 50, 3, and 11% of the patients, respectively. Multivariate analysis showed that reductions of the amplitude of the sensory action potential of >11.5% in the median nerve between baseline and four cycles of chemotherapy (odds ratio=5.603, p=0.031) and of >22.5% in the sural nerve between four and eight cycles of chemotherapy (odds ratio=5.603, p=0.031) were independently associated with the risk of developing grade-3 OIPN.ConclusionsWhile the severity of OIPN can improve after oxaliplatin discontinuation, more than half of the patients in this study still had OIPN at 1 year after discontinuation. Early changes in the NCS results for sensory nerves can predict the development of severe OIPN during treatment.

Predictive Biomarkers of Oxaliplatin-Induced Peripheral Neurotoxicity

“…Several longitudinal studies, including NCS during OXA therapy, have showed a significant progressive decrease in sensory nerve action potentials (SNAPs) and preservation of motor action compound (CMAPs), in keeping with the presence of an axonal sensory neuropathy, and consistent with the clinical symptoms and signs worsening during the treatment [ 17 , 41 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ]. NCS are capable of objectively assessing the extent of peripheral nerve damage and may also facilitate the identification of patients that manifest subclinical peripheral neuropathy prior to the onset of clinically significant neurotoxicity.…”

Effects of 7?11 cycles adjuvant FOLFOX chemotherapy on the prognosis of patients with stage III colon cancer

“…A prospective study of Korean colorectal cancer patients treated with 12 cycles of adjuvant FOLFOX revealed that 94% showed signs of OIPN after the completion of treatment, and 14% of patients showed grade 3 OIPN. 11) OIPN persisted in 64% of patients 1 year after the end of treatment, with 11% of patients showing grade 3 toxicity, and the frequency and severity of OIPN increased with repeated cycles of chemotherapy. 11) Because there is no specific method to prevent OIPN and treatment entails only conservative management, there is continued concern about how to reduce the use of oxaliplatin.…”

“…11) OIPN persisted in 64% of patients 1 year after the end of treatment, with 11% of patients showing grade 3 toxicity, and the frequency and severity of OIPN increased with repeated cycles of chemotherapy. 11) Because there is no specific method to prevent OIPN and treatment entails only conservative management, there is continued concern about how to reduce the use of oxaliplatin. 12) One way to reduce the frequency and severity of OIPN may be to reduce the number of chemotherapy cycles.…”

Is TRPA1 Burning Down TRPV1 as Druggable Target for the Treatment of Chronic Pain?

“…Indeed, TRPA1 blockers or genetic ablation decreased nociceptive changes observed in animal models of neuropathic pain [60,154,155,156]. Another standard model of neuropathic pain is the one induced by the administration of chemotherapy drugs that may produce, as side effects, intense cold and mechanical hyperalgesia and/or allodynia, limiting administration to patients [157,158]. Similar to nerve injury models, the blockage of TRPA1 counteracted pain in several models of chemotherapy-induced neuropathic pain [159,160].…”