New guidelines on managing chemotherapy-induced neurotoxicity

  • Ann Oncol

  • Oncology guidelines update
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The European Society for Medical Oncology (ESMO) has partnered with the European Oncology Nursing Society (EONS) and the European Association of Neuro-Oncology (EANO) to produce clinical practice guidelines on the management of chemotherapy-induced peripheral neurotoxicity (CIPN) and central neurotoxicity. A summary of the key recommendations is provided below.

Assessment of CIPN

  • Evaluate for symptoms of CIPN before every treatment cycle. A practical assessment approach for CIPN is provided in the guidelines.
  • Serum neurofilament light (NfL) determination is not currently recommended for assessment in routine practice.
  • Electromyography (EMG) with nerve conduction may identify pre-existing, sometimes still subclinical, neuropathy.
  • Conventional nerve conduction parameters are not suitable to monitor the severity of CIPN during therapy.
  • In small fibre neuropathies (eg, bortezomib), skin biopsy may demonstrate degeneration of small C (Heat) and Aδ (Cold) fibres.

Treatment of CIPN

SSRIs:

  • Duloxetine (the only agent recommended with level I evidence for treatment of neuropathic pain - 30 mg/day for one week, then 60 mg/day [I, B].
  • Venlafaxine 50 mg initially, followed by 37.5 mg twice/day [II, C].

Anticonvulsants:

  • Gabapentin targeted dose: 2700 mg/day [II, D].
  • Pregabalin targeted dose: 300 mg twice/day [II, C].         
  • Lamotrigine starting dose: 25 mg/day, targeted dose: 300 mg/day [II, E].

Tricyclic antidepressants:

  • Amitriptyline starting dose: 10 or 25 mg/day targeted dose: 50 mg/day [II, C].
  • Nortriptyline targeted dose: 100 mg/day [II, D].

Opioids:

  • Tramadol 200-400 mg in 2 (extended release) or 3 doses [II, C].
  • Stronger opioids as salvage treatment.

Other oral therapy

  • Glutamine: Modest evidence for efficacy in children; so far, no recommendation in adults.
  • There is no evidence supporting the use of NSAIDs or glucocorticoids.

Topical treatments:

  • Topical 1% menthol creme should be considered as it is a low-cost intervention with no reported harmful effects. Apply to affected area and corresponding dermatomal region of spine twice/day. [III, B].
  • Topical baclofen, amitriptyline, ketamine gel may be considered [II, C].  
  • Topical 2% ketamine and 4% amitriptyline is not recommended. [I, D].
  • Capsaicin 8%-containing patches can be considered [III, C].

Other treatments

  • Acupuncture may be considered in selected patients [II, C].
  • Scrambler therapy (noninvasive cutaneous electrostimulation) is not recommended [II, D].
  • Spinal cord stimulation (SCS) may be discussed only for patients with truly refractory neuropathic pain [V, C].
  • Weak recommendation in favour of electroencephalogram (EEG)-based neurofeedback [II, C].
  • Otoprotective treatment with sodium thiosulfate cannot currently be recommended as standard treatment [I, C].
  • Cryotherapy with frozen socks or gloves can be considered [II, C].
  • Compression therapy using surgical gloves can be considered as a preventive measure [III, C]. 

Management of central neurotoxicity

  • Methylene blue and/or thiamine and/or glucose 5% cannot be recommended as prophylactic or therapeutic measures [V, D].
  • Prophylactic exogenous albumin is not recommended [V, D].
  • Treatment of ifosfamide-induced acute encephalopathy includes discontinuation of ifosfamide, correction of electrolytes (if deranged), and symptom control [V, B].
  • Very stringent control of blood pressure is crucial, especially when posterior reversible leukoencephalopathy syndrome (PRES) is present [V, B].
  • PRES requires cessation of anticancer therapy and antiepileptic treatment for seizures [V, B].
  • Considered steroids for myelopathy or high-dose folate metabolites in patients with MTX-induced myelopathy [V, C].
  • No recommendation is made on the prevention or treatment of progressive multifocal leukoencephalopathy (PML).

The complete guidelines and the new CIPN assessment tool are available here.