Cisplatin-induced peripheral neurotoxicity is dependent on total-dose intensity and single-dose intensity

Cisplatin is one of the most effective chemotherapeutic drugs available for a variety of different solid tumors. Like all anticancer drugs, cisplatin has serious toxic side effects. The most severe toxic side effects involve the kidneys and the brain. However, the administration of excessive amounts of fluids to the patient in combination with diuretics can protect the kidneys from cisplatin toxicity during chemotherapeutic treatment. Therefore, it is cisplatin's neurotoxicity which limits the doses which may be administered. Cisplatin toxicity may cause hearing loss and global metabolic problems of the brain and spinal cord. However, the most likely reason for an individual patient to withdraw from cisplatin chemotherapy is toxic effects on the peripheral nerves. A study was conducted to determine if varying the schedule of cisplatin dose could reduce the likelihood of peripheral neurotoxicity even though the total cisplatin dose remained the same. Sixty women with advanced ovarian cancer were divided into three equal groups. All patients received a total dose of 450 milligrams of cisplatin per square meter of body area. One group received cisplatin in a standard dose protocol: 75 milligrams per square meter given every three weeks for six cycles. The second and third groups received 50 milligrams cisplatin per square meter weekly for nine weeks; the third group received cyclophosphamide in addition to the cisplatin. The effect of the chemotherapeutic treatment on the ovarian cancer was determined by second-look laparotomy, in which the surgeon opens the abdomen and makes direct observations; no differences in treatment effectiveness were observed for the three treatment groups. Measurements of sensory nerve function, however, demonstrated that the first group, the more conventional treatment protocol, resulted in significantly greater abnormal nerve function than the other two schedules. The reduction in measured abnormalities may indicate that the neurotoxic limits were not approached as closely in the two groups receiving the less conventional schedule of treatment. This suggests that alterations in standard treatment protocols may reduce the likelihood of one of the more feared and disabling side effects of cisplatin treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)