Approach to chemotherapy-induced peripheral neuropathy

Introduction

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common side effects of cytotoxic chemotherapy and presents as a distal, symmetric polyneuropathy ( Table 28.1 ). Rates of CIPN depend on the agent being used but tend to occur in 60–70% of patients who receive neurotoxic agents. ^, According to one metaanalysis, the aggregate prevalence of CIPN is estimated to be 48%. Incidence is highest among patients receiving platinum-based drugs and taxanes, and slightly lower for bortezomib and vinca alkaloids. ^,

Clinical presentation

CIPN is generally a small fiber, sensory predominant polyneuropathy that is dose-dependent. Patients develop neuropathic symptoms in a distal, symmetric distribution, which typically include numbness, tingling, cramping, and at times weakness or burning pain in the feet and hands. When large fiber proprioceptive afferents are involved, patients may also develop impaired balance and falls, which can further impair quality of life. If CIPN is not recognized and chemotherapy doses not adjusted, delayed, or discontinued, permanent disability will occur. Most patients develop numbness first in the feet and hands. Neuropathic pain, motor weakness, or autonomic dysfunction are uncommon but may be seen with continued treatment as symptoms progress.

Clinical manifestations vary with the type of neurotoxic agent. For example, taxane chemotherapies, commonly used in treating breast, gynecologic, head/neck, and thoracic malignancies, tend to cause a sensory neuropathy with prominent numbness and tingling. Burning neuropathic pain occurs in only about 30–40% of taxane-induced CIPN. Neuropathy starts in the mid-to-late portion of the treatment and persists after patients complete their chemotherapy, often for weeks to months after the final dose. In contrast, oxaliplatin, which is commonly employed in regimens for gastrointestinal cancers, causes immediate cold hypersensitivity that occurs after each infusion as well as neuropathic pain, numbness, and tingling that worsens over time.

CIPN frequently persists after completion of cytotoxic therapy in about half of patients where it becomes a significant source of survivorship morbidity. In one study, CIPN was present in 68.1% of individuals when measured in the first month after chemotherapy, 60% at 3 months, and 30% at 6 months or more. Some patients even report neuropathic symptoms that persist for years after their last dose of chemotherapy. In rare cases, patients with no symptoms or only mild neuropathy during treatment go on to develop CIPN or experience paradoxical intensification of symptoms following the cessation of chemotherapy, often referred to as “coasting.” Thus, predicting who is at risk for CIPN is a priority.