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?

 

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).

Shah A, Hoffman EM, Mauermann ML, et al. Incidence and disease burden of chemotherapy-induced peripheral neuropathy in a population-based cohort. J Neurol Neurosurg Psychiatry. 2018 Jun;89(6):636–641.

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,

Loprinzi CL, Lacchetti C, Bleeker J, 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

these drugs damage peripheral nerves via different pathologic means, although they share some similarities. 

 

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 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.

• 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.

Majithia N, Smith TJ, Coyne PJ, et al. Scrambler Therapy for the management of chronic pain. 2016 Jun;24(6):2807–2814.

 

The National Cancer Institute offers advice on how to prevent and manage problems related to CIPN.

Nerve Problems (Peripheral Neuropathy) and Cancer Treatment. National Cancer Institute. January 15, 2020.

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.

Persistent Peripheral Neuropathy Increases Fall Risk among Cancer Survivors. National Cancer Institute. February 5, 2016.