Chemotherapy-induced peripheral neuropathy (CIPN) is damage and dysfunction of the peripheral nervous system secondary to chemotherapeutic agents, including platinum agents, taxanes, vinca alkaloids, thalidomide, bortezomib, and ixabepilone (Table 96.1). CIPN commonly occurs in 30% to 40% of patients, but its incidence can vary from 0% to 70% [1]. The degree of neuronal damage is dependent on many factors, such as the chemotherapeutic agent, the frequency and duration of therapy, the cumulative dose, the use of other neurotoxic agents, and the presence of preexisting neuropathies, most commonly from diabetes [1]. The severity of neuropathy generally increases until cessation of treatment. However, symptoms associated with platinum drugs may progress for weeks to months after treatment completion, a phenomenon called the “coasting” effect [2]. Many scales have been proposed to assess CIPN but lack standardization and reproducibility. The most widely used tool is the National Cancer Institute Common Terminology Criteria for Adverse Events (v4.03) (Table 96.2) [3]. Another scale is called the Total Neuropathy Score, which appears to be more sensitive in detecting changes in CIPN [4].

Table 96.1

Most Common Chemotherapeutic Agents Known to Induce Neuropathy

Drug	Mechanism of Action
Platinum compounds (cisplatin, carboplatin, oxaliplatin)	Damages DNA in dorsal root ganglion, causing neuronopathy or ganglionopathy with sensory axonal neuropathy
Vinca alkaloids (vincristine, vinblastine, vinorelbine, vindesine) Taxanes (paclitaxel, paclitaxel albumin-stabilized nanoparticle formulation [Abraxane], docetaxel)	Antimicrotubule agents that inhibit axonal transport, causing sensorimotor axonal neuropathy

Table 96.2

National Cancer Institute Common Terminology Criteria for Adverse Events (v4.03), Motor and Sensory Combined

Grade	Description	Action
0	Normal	No intervention
1	Asymptomatic, clinical or diagnostic observations only, weakness on examination only, loss of deep tendon reflexes or paresthesia	No intervention
2	Moderate symptoms, limiting instrumental activities of daily living	Decrease dosage
3	Severe symptoms, limiting self-care activities of daily living, assistive devices indicated	Decrease dosage or discontinue treatment
4	Life-threatening consequences, disabling	Discontinue treatment, urgent intervention indicated
5	Death

Symptoms

The onset of symptoms can be sudden or slowly progress over time. Symptoms can vary by what types of nerve fibers are affected. Sensory nerves are more commonly affected first because they have small fibers, they have little capacity for regeneration, and their cell bodies are located in dorsal root ganglion, where they are outside the protective blood-brain barrier. The dorsal root ganglion has a high supply of capillaries that are highly permeable to toxic compounds in the blood [5]. Patients can present with symmetric, distal, length-dependent, “stocking-glove” distribution of painful paresthesia, dysesthesia, cold sensitivity, allodynia, tingling, and numbness. The patients also may report muscle cramps and pain described as burning, lancinating, shock-like, or electric. Motor nerve fiber cell bodies located in the spinal cord are less affected as they are protected within the blood-brain barrier and they also have the capacity for distal sprouting and regeneration. Patients usually present with muscle weakness, myalgias, and difficulty in walking. If autonomic nerves are affected, patients can present with orthostatic hypotension, constipation, urinary retention, irregular heart rate, and sexual dysfunction [6].