Long‐term course of oxaliplatin‐induced polyneuropathy: a prospective 2‐year follow‐up study

Briani, Chiara; Argyriou, Andreas A.; Izquierdo, Cristina; Velasco, Roser; Campagnolo, Marta; Alberti, Paola; Frigeni, Barbara; Cacciavillani, Mario; Bergamo, Francesca; Cortinovis, Diego; Cazzaniga, M.; Bruna, Jordi; Cavaletti, Guido

doi:10.1111/jns.12097

Cited by 80 publications

(58 citation statements)

References 34 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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“…Whereas treatment with, for example, the third generation platinum compound oxaliplatin (OX) can achieve high rates of disease free survival from colorectral cancer (Andre et al, 2009), OX treatment is often accompanied by severe and persistent neurotoxic symptoms, which grow more prevalent with the increasing long-term survival of the cancer patient population (Aaronson et al, 2014; Fehrenbacher, 2015). Accumulating doses of OX can result in numbness, and tingling in toes and feet (Argyriou et al, 2012; Avan et al, 2015), as well as sensory ataxia with imbalance and falls (Bennett et al, 2012; Tofthagen et al, 2012), some or all of which can persist in a substantial number of patients for years after the cessation of chemotherapy (Kiernan, 2007; Park et al, 2011b; Briani et al, 2014). Finding a solution to this urgent and growing problem is hindered by inadequate understanding of the pathogenesis of neurotoxic symptoms.…”

Section: Introductionmentioning

confidence: 99%

A novel path to chronic proprioceptive disability with oxaliplatin: Distortion of sensory encoding

Vincent

Wieczerzak

Gabriel

et al. 2016

Neurobiology of Disease

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Persistent neurotoxic side effects of Oxaliplatin (OX) chemotherapy, including sensory ataxia, limit the efficacy of treatment and significantly diminish patient quality of life. The common explanation for neurotoxicity is neuropathy, however the degree of neuropathy varies greatly among patients and appears insufficient in some cases to fully account for disability. We recently identified an additional mechanism that might contribute to sensory ataxia following OX treatment. In the present study, we tested whether that mechanism, selective modification of sensory signaling by muscle proprioceptors might result in behavioral deficits in rats. OX was administered once per week for seven weeks (cumulative dose i.p. 70 mg/kg) to adult female Wistar rats. Throughout and for three weeks following treatment, behavioral analysis was performed daily on OX and sham control rats. Compared to controls, OX rats demonstrated errors in placing their hind feet securely and/or correctly during a horizontal ladder rung task. These behavioral deficits occurred together with modification of proprioceptor signaling that eliminated sensory encoding of static muscle position while having little effect on encoding of dynamic changes in muscle length. Selective inability to sustain repetitive firing in response to static muscle stretch led us to hypothesize that OX treatment impairs specific ionic currents, possibly the persistent inward Na currents (NaPIC) that are known to support repetitive firing during static stimulation in several neuron types, including the class of large diameter dorsal root ganglion cells that includes muscle proprioceptors. We tested this hypothesis by determining whether the chronic effects of OX on the firing behavior of muscle proprioceptors in vivo were mimicked by acute injection of NaPIC antagonists. Both riluzole and phenytoin, each having multiple drug actions but having only antagonist action on NaPIC in common, reproduced selective modification of proprioceptor signaling observed in OX rats. Taken together, these findings lead us to propose that OX chemotherapy contributes to movement disability by modifying sensory encoding, possibly via a chronic neurotoxic effect on NaPIC in the sensory terminals of muscle proprioceptors.

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“…OIPN has been reported as dose-dependent, with symptoms more likely to occur as the cumulative dose exceeds 780–850mg/m 2 . Unlike acute OIPN that is transient, chronic OIPN can persist for months or years 12,13 and includes pain, numbness, and dysesthesias that lead to reduced quality of life and function 14 . Little is known about how individual symptoms are related and whether they co-occur, which limits the management options and early identification of OIPN.…”

Section: Introductionmentioning

confidence: 99%

Oxaliplatin-Induced Peripheral Neuropathy and Identification of Unique Severity Groups in Colorectal Cancer

Griffith

Zhu

Johantgen

et al. 2017

Journal of Pain and Symptom Management

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Context Oxaliplatin-induced peripheral neuropathy (OIPN) is a dose limiting toxicity of oxaliplatin and affects most colorectal cancer (CRC) patients. OIPN is commonly evaluated by patient symptom report, using scales to reflect impairment. They do not discriminate between unique grouping of symptoms and signs, which impedes prompt identification of OIPN. Objective Our study objective was to identify clusters of symptoms and signs that differentiated underlying clinical severity and segregated patients within our population into OIPN subgroups. Methods Chemotherapy naïve CRC patients (N=148) receiving oxaliplatin were administered the Total Neuropathy Score clinical (TNSc©), which includes symptom report (sensory, motor, autonomic) and sensory examination (pin sense, vibration, reflexes). The TNSc© was administered prior to chemotherapy initiation (T0), and following cumulative doses of oxaliplatin 510-520 mg/m2 (T1) and 1020-1040 mg/m2 of oxaliplain (T2). Using mean T2 TNSc© scores, latent class analysis (LCA) grouped patients into OIPN severity cohorts. Results LCA categorized patients into 4 distinct OIPN groups: low symptoms and low signs (N=54); low symptoms and intermediate signs (n=44); low symptoms and high signs (n=21); and high symptoms and high signs (n=29). No differences were noted among OIPN groups on age, sex, chemotherapy regimen, or cumulative oxaliplatin dose. Conclusion We identified OIPN patient groups with distinct symptoms/signs, demonstrating variability of OIPN presentation regardless of cumulative oxaliplatin dose. Over half of the sample had positive findings on OIPN examination despite little or no symptoms. Sensory examination of all patients receiving oxaliplatin is indicated for timely identification of OIPN, which will allow earlier symptom management.

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Long‐term course of oxaliplatin‐induced polyneuropathy: a prospective 2‐year follow‐up study

Cited by 80 publications

References 34 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

A novel path to chronic proprioceptive disability with oxaliplatin: Distortion of sensory encoding

Oxaliplatin-Induced Peripheral Neuropathy and Identification of Unique Severity Groups in Colorectal Cancer

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