Neurologic Complications of Cancer Chemotherapy
Section snippets
Platinum-Based Agents
Neurotoxicity is commonly seen with the platinum agents, more so with cisplatin than oxaliplatin or carboplatin. Although cisplatin has poor penetration through the blood-brain barrier, it has a propensity to enter dorsal root ganglia (DRG) and peripheral nerves where concentrations can be four to five times that found in the brain.1 It has been postulated that once in the DRG, cisplatin causes neuronal apoptosis.2 It produces an axonal neuropathy with secondary demyelination that predominantly
Methotrexate
Methotrexate (MTX) is the most commonly used antifolate agent and has multiple modes of administration including oral, intravenous (IV), IA, and intrathecal (IT). As such, the clinical manifestation of neurotoxicity varies depending on the manner of delivery and cumulative dose, and also is influenced by the concurrent use of additional therapies such as radiation.
Paclitaxel and Docetaxel
Following paclitaxel therapy, approximately 60% of patients develop a peripheral neuropathy, although in only 10% does it become debilitating.4, 42 Both small and large sensory fibers are involved typically, and patients present with paresthesias in the hands and feet with loss of ankle jerks on examination. Concurrent or prior use of cisplatin increases the risk of developing neuropathy.43, 44 Other risk factors include higher cumulative doses as well as higher single doses given over shorter
Thalidomide
Originally designed as a sedative, thalidomide gained notoriety in the 1960s as a result of its teratogenic effects on the fetus causing developmental limb abnormalities. It was reinstated as a treatment for leprosy in 1998 by the US Food and Drug Administration, and has since been found to be useful in a range of malignancies. The most common neurologic side effects are somnolence and lethargy, occurring in 43% to 55% of patients.19 Neuropathy has also been described, and can be a
Antiemetics
Older medications used to treat nausea such as prochlorperazine (Compazine, Glaxo Smith Kline, Philadelphia, PA) and promethazine (Phenergan, Wyeth Pharmaceuticals, Madison, NJ) can cause dystonic reactions. Treatment includes discontinuation of the offending agent and use of anticholinergics in the acute phase. Although the newer generation of 5HT-3 receptor blockers are less likely to cause these symptoms, oculogyric crisis and dystonia have been reported with ondansetron (Zofran, Glaxo Smith
Conclusion
The range of neurologic complications associated with chemotherapeutic treatments for cancer is broad. Multiple agents have similar side effects such as peripheral neuropathy and encephalopathy. The task of distinguishing the cause of various toxicities can be complex and the etiology is often multifactorial. Occasionally, prevention of side effects is possible with appropriate pretreatment screening and careful follow up. For example, patients preparing to begin cisplatin or vincristine should
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