Helping your cancer patients with their neuropathy

By Naveed Saleh, MD, MS | Medically reviewed by Jeffrey A. Bubis, DO, FACOI, FACP
Published March 29, 2023

Key Takeaways

  • Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition that can occur at any time during chemotherapy treatment and persist for years or for life.

  • The symptoms of CIPN vary by cytotoxic agent, with some similarities and differences only recently being elucidated.

  • There’s a dearth of effective treatment and preventive options for CIPD, although measures such as dose adjustment of chemotherapeutic agents can be discussed with patients whose CIPD is severe.

Chemotherapy of various types can damage the peripheral nerves. These nerves coordinate movement of the extremities and detect sensation in the hands and feet. This iatrogenic condition is referred to as chemotherapy-induced peripheral neuropathy (CIPN).

CIPN can present at any time during chemotherapy, and symptoms can persist long-term. Unfortunately, there are few effective interventions for CIPN, making prevention of further injury an important consideration.

How common is CIPN?

The incidence of CIPN is high in patients receiving neurotoxic therapy—especially during the first 2 years following exposure. 

Results from a US study published in the Journal of Neurology, Neurosurgery & Psychiatry indicated that, of the 509 patients in the study, 52.7% developed CIPN following incident exposure, with a median time to first-documented symptoms of 71 days (n=509).[] Only 13.8% of the patients with CIPN received a formal ICD-9 diagnosis.

In other findings, pain symptoms and the use of pain medications were higher in patients with CIPN. The 5-year survival in those with CIPN was higher than those without the condition (55.2% v. 36.1%). Among those with CIPN who survived 5 or more years, substantial impairments were common, and these patients were more likely to receive opioids (OR: 2.0).

What are the symptoms?

Many cytotoxic drugs can cause CIPN, including taxanes, platinums, proteosome inhibitors like bortezomib, vinca alkaloids, epothilones, and eribulin. As discussed in an ASCO guideline update on CIPN,[] these drugs damage peripheral nerves via different pathologic means, although they share some similarities. 

Depending on the cytotoxic agent used and the peripheral nerves affected, sensory, autonomic, or motor deficits can result.

Specific clinical presentations of CIPN associated with the different agents are ill-defined, as studies of CIPN have used inconsistent measurement methods. Recently, however, there have been studies that employed the same validated neuropathy measurement tools. These studies have elucidated the clinical manifestations secondary to two of the most common chemotherapy offenders: paclitaxel and oxaliplatin.

The chronic neuropathies due to paclitaxel and oxaliplatin are primarily sensory, as opposed to motor or autonomic. 

Numbness, tingling, and pain are all common. 

Numbness and tingling are the more prominent symptoms, and they occur before pain. The stocking-glove pattern of symptoms usually starts at the level of the fingers and toes and progresses proximally as the condition becomes more severe.

The neuropathy symptoms differ between the two drugs in that paclitaxel-induced chronic neuropathy symptoms occur more frequently in the lower extremities than the upper extremities during treatment, whereas the converse is true with oxaliplatin.

Following the completion of chemotherapy, paclitaxel-induced neuropathy tends to improve over several months, but the neuropathy  from oxaliplatin worsens for 2 to 3 months (the coasting phenomenon) and then usually improves.

What are the treatments?

For the ASCO update, an Expert Panel analyzed the literature on the prevention and treatment of CIPN in adult cancer patients.

The ASCO recommendations are evidence-based and enlightened by clinical experience.

  • Oncologists should review the risks and benefits of CIPN-inducing agents in patients who have an underlying neuropathy or predisposing comorbidities such as diabetes or hereditary neuropathy.

  • Clinicians should not promote the use of acetyl-l-carnitine to prevent CIPN.

  • No recommendations could be made on various other potentially preventive interventions, including exercise, acupuncture, compression therapy, ganglioside-monosialic acid (GM-1), or cryotherapy.

  • Various agents—including antidepressants, antiseizure medications, metformin, calcium-channel blockers, and cannabinoids—should not be offered to patients with CIPN as preventive therapy.

  • In patients with intolerable CIPN or functional nerve impairment, physicians should confer with their patients regarding dose delay, dose reduction, dose cessation, or substitution with another drug that does not induce CIPN.

  • In patients experiencing painful CIPN, oncologists can offer duloxetine.

  • As treatment, no recommendations can be made regarding exercise, tricyclic antidepressants, acupuncture, cannabinoids, gabapentin/pregabalin, scrambler therapy, or topical agents containing baclofen, amitriptyline HCL, or ketamine. 

Scrambler therapy is a non-invasive pain-modifying technique that uses transcutaneous electrical stimulation of pain fibers to re-organize maladaptive signaling pathways. Currently, only limited evidence supports its use.[]

The National Cancer Institute offers advice on how to prevent and manage problems related to CIPN.[] These include protecting the hands and feet (proper shoes; proper cold-weather wear), preventing falls,  slowing down or asking for help when completing difficult tasks, and taking care in the shower. The risk of falls is substantially increased in women with CIPN, which underscores the importance of safety precautions.[] 

What this means for you

CIPN is a disabling condition that erodes quality of life in those affected. The presentation and severity of CIPN varies by cytotoxic agent used, the duration of therapy, comorbidities, and specific nerves affected. Patients should be encouraged to share their symptoms with their physician so that these issues can be factored into the treatment plan. Physicians should keep themselves apprised of effective mitigation strategies to reduce further nerve injury and to moderate the associated functional limitations and safety risks to the patient. 

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