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

Article Abstract:

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.)

Methods, Cisplatin

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Prolonged response to carboplatin in an infant with brain stem glioma

Article Abstract:

The brain stem controls breathing and the heart rate, as well as other functions critical for life. When a tumor occurs in this region of the brain, it is generally not possible to surgically remove it, and radiation is most often applied. The average survival of patients with gliomas in the brain stem is about 15 months after radiation therapy. The use of radiation therapy is questionable, in the treatment of infants, since the therapy may affect the normal development of the brain. For this reason, a 15-month old child with a glioma in the brain stem was treated with the chemotherapeutic drug carboplatin rather than with radiation. The parents of the patient had noticed crossed eyes at four months of age, and spastic legs at nine months. At one year of age a CT scan showed no abnormalities, but neurological deterioration continued. At 15 months of age, MRI revealed the presence of a brain tumor and showed that the tumor was continuing to grow on the upper surface of the brain stem and the cervical region of the spinal cord. A biopsy confirmed that the patient had a low-grade astrocytoma, a tumor made up of neuroglial tissue. The patient was treated with carboplatin. Clinical improvements were first noticed three moths after the beginning of therapy, and at 10 months the regression of the tumor could be documented on MRI. At the last MRI scan, residual tumor could be seen which had not changed in the previous year. The patient remains alive over 36 months after the initiation of treatment. The patient's intellectual ability is above normal, within the top five percent, indicating that the choice oaf carboplatin achieved its goal of sparing cognitive development. However, there is some impairment in motor development. While there is every reason to be hopeful, the authors caution that there is little data on which to base an estimate of the chances of a sustained remission. For patients with low-grade brainstem tumors treated with radiation, relapses are uncommon after two years, but relapses up to 15 years after diagnosis have been documented. (Consumer Summary produced by Reliance Medical Information, Inc.)

Brain tumors, Carboplatin, Astrocytoma, Astrocytomas

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