Guideline sources The following summarized guidelines for the evaluation and management of chemotherapy-induced peripheral neuropathy (CIPN) are prepared by our editorial team based on guidelines from the European Oncology Nursing Society (EONS/EANO/ESMO 2020), the American Society of Clinical Oncology (ASCO 2020), and the American Cancer Society (ACS 2013). 1 2 3 4 4 4 5 Definition CIPN is a common complication of chemotherapy, that is predominantly characterized by sensory neuropathy and may be accompanied by motor and autonomic changes. 4 Epidemiology CIPN can occur in patients with platinum-based antineoplastic agents (oxaliplatin, cisplatin, carboplatin), epothilones (ixabepilone), taxanes (paclitaxel, docetaxel), immunomodulatory drugs (thalidomide), vinca alkaloids (vincristine, vinblastine, vinorelbine, vindesine), and proteasome inhibitors (bortezomib). 4 Disease course https://web.pathway.md/diseases/recNTriLP0y7f00NE 1/5 6/29/23, 3:50 AM Chemotherapy-induced peripheral neuropathy Pathway CIPN may affect sensory, motor, and/or autonomic functions to varying degrees. Symptoms include numbness, tingling, altered touch sensation, impaired vibration, paresthesias, dysesthesias, spontaneous burning, shooting or electric shock-like pain, allodynia, hyperalgesia, distal weakness, gait and balance disturbances, impaired movements, orthostatic hypotension, constipation, and altered sexual/urinary function. Disease progression may lead to loss of sensation, paresis, complete patient immobilization, severe disability, and reduced quality of life. 4 Prognosis and risk of recurrence CIPN is not independently associated with increased mortality. 5 Calculator Calculator Eastern Cooperative Oncology G Karnofsky performance status s Guidelines 1. Diagnostic investigations Initial assessment: Obtain standardized assessment of CIPN including: baseline assessment and risk profile B long-term follow-up at > 2-3 months after treatment B calculation of Total Neuropathy Score or Total Neuropathy Score clinical version A objective evidence of neurological deficits A patient-reported outcomes, such as FACT/GOG-Ntx, EORTC QLQ-CIPN20, PNQ, CIPN-R- ODS A nerve conduction studies in the clinical trials setting. A Provide education regarding symptoms. Obtain ongoing patient surveillance B and assess the impact on function and quality of life. A 2. Medical management General principles: As per ESMO 2020 guidelines, focus on reduction or relief of neuropathic pain in patients experiencing chronic CIPN. B https://web.pathway.md/diseases/recNTriLP0y7f00NE 2/5 6/29/23, 3:50 AM Chemotherapy-induced peripheral neuropathy Pathway As per ACS 2013 guidelines, provide patient education, offer interventions to mitigate falls and injury risk, and counsel on lifestyle modifications, occupational therapy, and avoidance of neuropathy risk factors in patients with CIPN. B Modification/discontinuation of chemotherapy: as per ASCO 2020 guidelines, assess, and discuss with patients, the appropriateness of dose delaying, dose reduction, or discontinuation chemotherapy (or substituting with agents not causing CIPN) in patients developing intolerable neuropathy and/or functional nerve impairment. B Duloxetine: As per ASCO 2020 guidelines, consider offering duloxetine in patients with cancer experiencing painful CIPN. C As per ESMO 2020 guidelines, offer duloxetine for the treatment of neuropathic pain. B Other systemic agents: As per ASCO 2020 guidelines, insufficient evidence to support the use of the following agents for the treatment of CIPN outside the context of a clinical trial: gabapentin/pregabalin TCAs oral cannabinoids. I As per ESMO 2020 guidelines, consider offering the following agents for the treatment of neuropathic pain: venlafaxine pregabalin amitriptyline tramadol or strong opioids. C Topical agents: As per ASCO 2020 guidelines, insufficient evidence to support the use of a topical gel containing baclofen, amitriptyline hydrochloride, plus/minus ketamine for the treatment of CIPN outside the context of a clinical trial. I As per ESMO 2020 guidelines, consider offering topical low-concentration menthol cream in patients with CIPN. C 3. Nonpharmacologic interventions Physical therapies: As per ASCO 2020 guidelines, insufficient evidence to recommend exercise therapy or scrambler therapy for the treatment of CIPN outside the context of a clinical trial. I As per ESMO 2020 guidelines, offer physical exercise and functional training (such as vibration training) to reduce CIPN symptoms. B Acupuncture: https://web.pathway.md/diseases/recNTriLP0y7f00NE 3/5 6/29/23, 3:50 AM Chemotherapy-induced peripheral neuropathy Pathway As per ASCO 2020 guidelines, insufficient evidence to recommend acupuncture for the treatment of CIPN outside the context of a clinical trial. I As per ESMO 2020 guidelines, consider offering acupuncture for the treatment of CIPN symptoms in selected patients. C 4. Specific circumstances Patients with central neurotoxicity: do not use exogenous albumin for the prevention of ifosfamide-induced acute encephalopathy. Do not use methylene blue, thiamine, and/or glucose 5% for the prevention or treatment of ifosfamide-induced acute encephalopathy. D Show 6 more 5. Preventative measures Primary prevention: As per ASCO 2020 guidelines, assess the risks and benefits of agents known to cause CIPN in patients with underlying neuropathy and with conditions predisposing to neuropathy, such as diabetes and/or a family or personal history of hereditary neuropathy. B Show 3 more As per ESMO 2020 guidelines, obtain regular assessment for CIPN to discover potential symptoms early, before the neuropathy becomes irreversible. B Show 3 more 6. Follow-up and surveillance Monitoring for ototoxicity: Obtain a pure tone audiometry (including the wide spectrum of frequencies 500-8,000 Hz) for early detection of ototoxicity in adult patients receiving platinum agents. B Insufficient evidence to recommend prophylactic treatment with sodium thiosulfate because of the uncertainty regarding a possible tumor protection and lack of evidence in adult patients with cancer. I Clinical findings Symptoms Past medical history Burning sensation Diabetes mellitus Constipation Exposure to chemotherapy Diarrhea Orthostatic hypotension Dizziness Dysesthesia https://web.pathway.md/diseases/recNTriLP0y7f00NE 4/5 6/29/23, 3:50 AM Chemotherapy-induced peripheral neuropathy Pathway Gait disturbance Hearing loss Lightheadedness Loss of sensation Muscle cramps Muscle weakness Numbness Pain Paresthesia Sweating Tingling Tinnitus Vertigo Neurological exam Cutaneous allodynia Hyporeflexia Neuropathy Sensorineural hearing loss Sensory ataxia vibration sensation References 1. B Jordan, A Margulies, F Cardoso et al. Systemic anticancer therapy-induced peripheral and central neurotoxicity: ESMO EONS EANO Clinical Practice Guidelines for diagnosis, prevention, treatment and follow-up. Ann Oncol. 2020 Oct;31 10 1306 1319. Open 2. Susanna B Park, David Goldstein, Arun V Krishnan et al. Chemotherapy-induced peripheral neurotoxicity: a critical analysis. CA Cancer J Clin. 2013 Nov-Dec;63 6 419 37. Open 3. Charles L Loprinzi, Christina Lacchetti, Jonathan Bleeker et al. Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update. J Clin Oncol. 2020 Oct 1;38 28 3325 3348. Open 4. Renata Zaj czkowska, Magdalena Kocot-K pska, Wojciech Leppert et al. Mechanisms of Chemotherapy-Induced Peripheral Neuropathy. Int J Mol Sci. 2019 Mar; 20 6 1451. Open 5. Nathan P Staff, Anna Grisold, Wolfgang Grisold et al. Chemotherapy-induced peripheral neuropathy: A current review. Ann Neurol. 2017 Jun;81 6 772 781.2017 Jun;81 6 772 781. Open 6. Nathan P. Staff, Anna Grisold, Wolfgang Grisold et al. Chemotherapy-Induced Peripheral Neuropathy: A Current Review. Ann Neurol. 2017 Jun; 81 6 772 781. Open https://web.pathway.md/diseases/recNTriLP0y7f00NE 5/5