A recent update to guidelines from the American Society of Clinical Oncology (ASCO) on the prevention and management of chemotherapy-induced peripheral neuropathy (CIPN) in adult survivors of cancer provided a detailed review of the differences between symptoms of oxaliplatin-induced CIPN compared with paclitaxel-induced CIPN, and also revealed the dearth of evidence-based interventions for preventing and treating this adverse event of some cytotoxic therapies. These guidelines were published in the Journal of Clinical Oncology.
Chemotherapy-induced neuropathy has been associated with quality of life detriments in patients with cancer both during and following treatment with chemotherapy and can also lead to early discontinuation of cancer therapy, with adverse clinical outcomes.
Although CIPN has been reported to occur following administration of a variety of cytotoxic drugs and drug classes, including taxanes, platinums, vinca alkaloids, eribulin, epothilones, and bortezomib, the clinical manifestations of acute and chronic neuropathy associated with oxaliplatin, a platinum agent, and paclitaxel, a taxane, have been more thoroughly characterized.
Specifically, the severity of acute neuropathy is typically most severe 2 to 3 days following administration of each dose of either oxaliplatin or paclitaxel. However, characteristics of acute oxaliplatin-related neuropathy often include cold sensitivity and throat discomfort that is more intense with the second/subsequent doses compared with the first dose. In contrast, paclitaxel-related acute neuropathy is more likely to be associated with a pain syndrome that has a truncal/hip distribution and does not become worse with subsequent doses.
Both oxaliplatin and paclitaxel are associated with chronic sensory neuropathy characterized by numbness, tingling, and pain, with the upper extremities more likely to be affected in those treated with oxaliplatin and lower extremity involvement more common in patients receiving paclitaxel. Although chronic neuropathies with both drugs tend to improve over time, chronic oxaliplatin-related CIPN tends to worsen for 2 to 3 months following therapy cessation and then gradually improve while chronic paclitaxel-related CIPN is associated with gradual improvement following completion of cytotoxic therapy. However, chronic CIPN associated with either drug may persist for years in some patients.
Following a systematic review of the literature, with a focus on those studies published since the previous version of the guidelines was issued, the guidelines panel noted that a number of interventions which appeared to be promising when the previous version of these guidelines was published were no longer supportable.
For example, on the basis of new evidence, venlafaxine is no longer recommended for CIPN prevention, nor are tricyclic antidepressants and gabapentinoids considered reasonable to try when treating established CIPN outside the setting of a clinical trial.
Some of the key recommendations made by the guidelines panel with respect to the prevention of CIPN were as follows:
- Prior to administration of chemotherapy, clinicians should assess the risks and benefits of administering cytotoxic agents associated with CIPN to patients with neuropathy and those with conditions, such as diabetes, that predispose them to neuropathy.
- On the basis of high-level evidence, a strong recommendation was made against use of acetyl-L-carnitine.
- Additional research is needed to assess the risks and benefits of acupuncture, cryotherapy, compression therapy, exercise therapy, and ganglioside-monosialic acid (GM-1) before recommendations can be made for or against their use in this setting.
Regarding management of established CIPN, the following recommendations were included:
- Clinician-patient discussions should include the risk and benefits of reducing the dose of the cytotoxic agent associated with CIPN, as well as delays in the administration or termination of such cytotoxic therapy.
- On the basis of intermediate-level evidence, a recommendation of moderate strength was made for use of duloxetine for patients experiencing painful CIPN.
- A number of interventions, including acupuncture, tricyclic antidepressants, gabapentin/pregabalin, oral cannabinoids, and scrambler therapy, an approach involving use of an electroanalgesia device, were considered appropriate only within the context of a clinical trial.
The guidelines panel stressed that better interventions are needed to prevent and treat established CIPN.
Loprinzi CL, Lacchetti C, Bleeker J, et al. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: ASCO guideline update [published online July 14, 2020] J Clin Oncol. doi: 10.1200/JCO.20.01399