Neurotoxicity

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Cisplatin has been well documented to cause neuro-toxicity and ototoxicity. The peripheral neuropathy is predominantly sensory, manifested mostly by paresthesia and dysesthesia. These symptoms have been reported to persist beyond 6 years in about 30 to 40% of patients.1419 The long-term toxicity has been confirmed by other investigators.11 Nerve conduction studies have shown that the changes in conduction along peripheral and central pathways after tibial nerve stimulation are compatible with a toxic effect on the sensory root ganglia causing an axonal degeneration of central and peripheral nerve fibers. An increasing cumulative dose of cisplatin and simultaneous development of Raynaud's phenomenon increases the risk of neurotoxicity.15 The presence of abnormal nerve conduction studies in 50% of cases studied in the Royal Prince Alfred Hospital series14 suggests that higher single doses of cisplatin (eg, 100 mg/m2) may be more neurotoxic than are the more standard repeated daily low doses.

The clinical trial that resulted in BEP replacing PVB showed that the former is clearly a better option in the context of neurotoxicity. Specifically, the major toxicity of PVB is neuromuscular toxicity due to vinblastine, and the etoposide-containing regimen caused substantially fewer paresthesias (p = .02), abdominal cramps (p = .0008), and myalgias (p = .00002). These toxicities can impair manual dexterity for life and occupational activities, as well as cause significant discomfort from abdominal cramps, ileus, and myalgias. Thus, the difference in the rates of neuromuscular toxicity was both statistically and clinically significant.23

The ototoxicity associated with cisplatin is high-frequency hearing loss and is related to the cumulative dose and rate of infusion.32,33 It occurs in 20 to 40% of patients.15 Older age, serum creatinine level >1.5 mg/dL, cumulative doses of cisplatin, and preexisting hearing impairment are predictive for oto-toxicity (Figure 28-5). Although there may be some improvement over months to years, recovery to normal hearing is rare if a clinical or symptomatic hearing deficit is noted by a patient. When higher single doses of cisplatin are used, up to 60% of patients may exhibit occult audiometric changes.14

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