Late effects of oxaliplatin-induced peripheral neuropathy (LEON)—cross-sectional cohort study of patients with colorectal cancer surviving at least 2 years

Padman, Sunita; Lee, Jaein; Kumar, Rajiv; Slee, Mark; Hakendorf, Paul; Richards, Alison; Koczwara, Bogda; Kichenadasse, Ganessan; Sukumaran, Shawgi; Roy, Amitesh; Vatandoust, Sina; Karapetis, Christos S.

doi:10.1007/s00520-014-2423-9

Cited by 33 publications

(17 citation statements)

References 29 publications

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“…The post-treatment survivorship can be a distressed period of symptom burden, fatigue and reduced mental well-being [23,24]. The finding that neurotoxicity influences the patients' daily life is a similar result to earlier studies [14,15,[25][26][27][28][29], but those studies had cross-sectional cohorts, other disease stages, and different study designs.…”

Section: Discussionsupporting

confidence: 75%

The trajectory of neurotoxic side effects’ impact on daily life: a qualitative study

Drott

Starkhammar

Kjellgren

et al. 2016

Support Care Cancer

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Purpose To explore the experiences of oxaliplatin-induced neurotoxic side effects among patients with colorectal cancer (CRC), and how these side effects influenced their daily lives over time.Methods To assess neurotoxic side effects, ten patients were repeatedly interviewed. The patients were recruited from two hospitals in south of Sweden, had stage II-III CRC, and had been treated with adjuvant oxaliplatin postoperatively, from November 2013 to October 2015. They had received FOLFOX and XELOX, with a mean total dose of 791 mg oxaliplatin. After completed chemotherapy, at 3, 6 and 12 months into the post-treatment phase, 25 interviews were conducted and thematic analysis was used according to Braun and Clarke.Results Oxaliplatin-induced neurotoxicity affects patients in several ways in the long term. Four themes were identified: Expectation of cure, Dubiety, Normalization and Learn to live with neurotoxity. The findings of this study describe the trajectory of neurotoxicity and its impact on these patients' life situation. The findings confirmed that neurotoxicity is multi-faceted and that the experience of it changes over time. ConclusionThe desire to survive stimulates adaptations and strategies to manage daily life, and patients learn to live with the neurotoxic side effects. This study provides evidence that these patients need individual attention and support during the trajectory of neurotoxic side effects. Current care provision is inadequate due to lack of knowledge of the ways in which neurotoxicity impacts the patient's daily life. This study provides insights that could be used to develop more person-centered care.

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Section: Discussionsupporting

confidence: 75%

The trajectory of neurotoxic side effects’ impact on daily life: a qualitative study

Drott

Starkhammar

Kjellgren

et al. 2016

Support Care Cancer

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“…In terms of the pain characteristics listed in Table 2, it is difficult to compare our findings with previous reports because the majority of the studies of CIN in cancer survivors focused on the determination of occurrence rates using the National Cancer Institute Common Toxicity Criteria 65 or the occurrence rates for common symptoms on the CIPN20 scale. 11,16,19,66 In the one study that reported severity scores, 17 survivors were asked to rate the severity of numbness and tingling as a single item.…”

Section: Discussionmentioning

confidence: 85%

Chemotherapy-Induced Neuropathy in Cancer Survivors

Miaskowski

Mastick

Paul

et al. 2017

Journal of Pain and Symptom Management

100

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Context Evidence suggests that chemotherapy-induced neuropathy (CIN) is a significant problem for cancer survivors. However, a detailed phenotypic characterization of CIN in cancer survivors is not available. Objectives To evaluate between group differences in demographic and clinical characteristics, as well as in measures of sensation, function, and postural control, in a sample of cancer survivors who received a platinum and/or a taxane-based CTX regimen and did (n=426) and did not (n=197) develop CIN. Methods Survivors completed self-report questionnaires and underwent objective testing (i.e., light touch, pain sensation, cold sensation, vibration, muscle strength, grip strength, Purdue Pegboard test, Timed Get Up and Go Test, Fullerton Advanced Balance test). Parametric and non-parametric statistics were used to compare between group differences in study outcomes. Results Of the 426 survivors with CIN, 4.9% had CIN only in their upper extremities, 27.0% only in their lower extremities, and 68.1% in both their upper and lower extremities. Demographic and clinical characteristics associated with CIN included: older age, lower annual income, higher body mass index, a higher level of comorbidity, being born prematurely, receipt of a higher cumulative dose of chemotherapy, and a poorer functional status. Survivors with CIN had worse outcomes for all of the following objective measures: light touch, pain, temperature, vibration, upper and lower extremity function and balance. Conclusions This study is the first to provide a detailed phenotypic characterization of CIN in cancer survivors who received a platinum and/or a taxane compound. These data can serve as a benchmark for future studies of CIN in cancer survivors.

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“…Most patients recover from the neuropathy in a variable period of time, but long-term nerve damage can also occur, compromising the quality of life of these patients [12, 13]. Several studies have tried to explain OXLIN mechanism, but, so far, the molecular bases for it remain unknown.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms of SCN9A are associated with oxaliplatin-induced neuropathy

et al. 2017

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BackgroundOxaliplatin is a chemotherapy agent active against digestive tumors. Peripheral neuropathy is one of the most important dose-limiting toxicity of this drug. It occurs in around 60–80% of the patients, and 15% of them develop severe neuropathy. The pathophysiology of oxaliplatin neurotoxicity remains unclear. SCN9A is a gene codifying for a subtype sodium channel (type IX, subunit α) and mutations in this gene are involved in neuropathic perception. In this study we investigated whether SCN9A genetic variants were associated with risk of neurotoxicity in patients diagnosed of cancer on treatment with oxaliplatin.MethodsBlood samples from 94 patients diagnosed of digestive cancer that had received oxaliplatin in adjuvant or metastatic setting were obtained from three hospitals in Madrid. These patients were classified into two groups: “cases” developed oxaliplatin-induced grade 3–4 neuropathy (n = 48), and “controls” (n = 46) had no neuropathy or grade 1. The neuropathy was evaluated by an expert neurologist and included a clinical examination and classification according to validated neurological scales: National Cancer Institute Common Toxicity Criteria (NCI-CTC), Oxaliplatin-Specific Neurotoxicity Scale (OSNS) and Total Neuropathy score (TNS). Genotyping was performed for 3 SCN9A missense polymorphisms: rs6746030 (R1150W), rs74401238 (R1110Q) and rs41268673 (P610T), and associations between genotypes and neuropathy were evaluated.ResultsWe found that SCN9A rs6746030 was associated with protection for severe neuropathy (OR = 0.39, 95% CI = 0.16–0.96; p = 0.041). Multivariate analysis adjusting for diabetes provided similar results (p = 0.036). No significant differences in neuropathy risk were detected for rs74401238 and rs41268673.Conclusion SCN9A rs6746030 was associated with protection for severe oxaliplatin-induced peripheral neuropathy. The validation of this exploratory study is ongoing in an independent series.

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Late effects of oxaliplatin-induced peripheral neuropathy (LEON)—cross-sectional cohort study of patients with colorectal cancer surviving at least 2 years

Cited by 33 publications

References 29 publications

The trajectory of neurotoxic side effects’ impact on daily life: a qualitative study

The trajectory of neurotoxic side effects’ impact on daily life: a qualitative study

Chemotherapy-Induced Neuropathy in Cancer Survivors

Genetic polymorphisms of SCN9A are associated with oxaliplatin-induced neuropathy

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