Chemotherapy-induced peripheral neuropathy (CIPN) is a nerve-damaging side effect of antineoplastic agents in the common cancer treatment, chemotherapy.
Antineoplastic agents in chemotherapy are designed to eliminate rapidly dividing cancer cells, but they can also damage healthy structures, including the peripheral nervous system.
Researchers have conducted clinical trials and studies to uncover the various symptoms, causes, pathogenesis, diagnoses, risk factors, and treatments of CIPN.
Patients may experience numbness, tingling, altered touch sensation, gait and balance disturbances, burning pain, thermal allodynia or hyperalgesia, impaired vibration sense, extreme temperature sensitivity, paresthesia, and/or dysesthesia as part of sensory damage.
Motor symptoms of CIPN can include cramping, distal weakness, difficulty handling small objects, and impaired movements.
[3] A patient experiencing CIPN symptoms may have difficulty performing daily functionalities like walking, dressing themselves, writing, typing, and other activities related to the hands and feet.
[3] There are six main agent groups found in chemotherapy treatment that damage the sensory, motor, and autonomic neurons and therefore cause CIPN: 1) platinum-based compounds 2) taxanes 3) vinca alkaloids 4) epothilones 5) proteasome inhibitors 6) immunomodulatory drugs.
Additionally, functional neuronal deficits have been identified, independent of structural damage, e.g. ion channelopathy, impaired spike encoding in the central[5] and peripheral nervous system.
[3] 2) Taxanes, including paclitaxel (and protein-bound pactiltaxel e.g. abraxane), docetaxel, and cabazitaxel, are used to treat ovarian, breast, non-small cell lung, and prostate cancers.
Sensory side effects include paresthesias, dysesthesias, numbness, altered proprioception, and loss of dexterity in fingers and toes.
[3] Epothilones cause microtubule disruption (like taxane-based drugs), which impairs axonal transport and leads to hyperexcitability of peripheral neurons.
Bortezomib increases the production of sphingosine-1 phosphate, tumor necrosis factor α, and interleukin-1β, which ultimately leads to the development of neuropathic pain.
The side effects of receiving bortezomib include chronic, distal, and symmetrical sensory peripheral neuropathy and neuropathic pain syndrome which may last for weeks, months, or years after treatment completion.
Side effects of thalidomide-induced peripheral neuropathy include sensory symptoms, possible motor impairment, and gastrointestinal and cardiovascular autonomic manifestations.
[9] 2) A diagnosis of current or previous infectious disease such as Human Immunodeficiency Virus, Poliomyelitis, and Hepatitis B or C may increase a patient's risk.
The results provide clinicians with critical information on a patient's functional limitations in relation to their exposure to potentially neurotoxic chemotherapeutic agents.
[13][14] Physical examination to assess motor function, reflexes, gait and balance, and sensation also plays a key role in the diagnosis of CIPN.
[11] First, motor testing involves assessment of muscle tone and bulk, which may be decreased in patients with CIPN due to atrophy and hypotonia.
[1] In CIPN, sudomotor function, through electrochemical skin conductance allows for an objective quantification of small fiber impairment and is easy to implement in the clinic.
[15][16] A 2020 American Society of Clinical Oncology (ASCO) report provided an updated list of drugs tested and NOT recommended for prevention of CIPN.
[2] There are promising and safe behavioral interventions for CIPN that have been suggested to be helpful based on randomized clinical trials: 1) stretching 2) walking 3) resistance (strength) training 4) balance exercises 5) yoga 6) meditation.
[17] Walking can be effective in alleviating CIPN symptoms by boosting muscle power, increasing blood circulation, and improving balance.
[18] Resistance (strength) training has been tested in various clinical settings, and it has been shown to be helpful in treating CIPN symptoms such as temperature sensitivity, numbness, and tingling.
Somatic yoga is often used by cancer survivors for symptom management, and it has been found to improve physical and mental health for patients with CIPN.
Yoga's emphasis on dynamic movement can lead to improvement in flexibility, strength, balance, and stability, all of which may be negatively impacted by CIPN.
Cryotherapy for patients with CIPN involves wearing frozen gloves and socks or ice packs to prevent and relieve symptoms.
These studies are not conclusive, and additional randomized trials investigating the efficacy of cryotherapy and compression therapy for prevention and treatment of CIPN are ongoing.
[23] One randomized trial evaluating the success of scrambler therapy in alleviating CIPN symptoms found no significant differences between treatment and control groups (Smith et al.
[24] Another trial testing scrambler therapy with patients with CIPN found patient-reported neuropathy symptoms and quality-of-life to be improved from baseline status.
Overall, more research is needed to advance understanding of CIPN etiology, risk assessment, development, and treatment (e.g. duloxetine, genetic targets, and exercise).