Incidence of neuropathy in 395 patients with ovarian cancer treated with or without cisplatin

Article Abstract:

Cisplatin is a remarkable chemotherapeutic agent that is yielding long-term survival among cancer patients who would not have been likely to survive 15 years ago. In the case of ovarian cancer, even patients with advanced disease may have a 30 percent chance of survival. This success does not come without a cost, however, and cisplatin can produce serious side effects. These side effects include neurotoxicity and kidney damage. The kidney damage may be controlled by the appropriate use of forced hydration and diuretics, making neurotoxicity the most important limiting factor when determining the cisplatin dosage. Cisplatin seems to affect predominantly sensory systems, and may cause deafness, sensations of tingling, loss of vibratory sensation, and the inability to sense the body's movements and position. The damage is cumulative, and in 30 to 50 percent of cases is irreversible. The cases of 387 patients treated over a four-year period for ovarian cancer were tabulated with respect to neurotoxicity. The treatment of 292 patients included cisplatin therapy. Among these patients, 47 percent experienced some sort of neurotoxic effect, compared with 25 percent of the remaining patients. It should be mentioned, however, that the long-term survival of the cisplatin-treated patients was almost 2.5 times that of the patients who did not have cisplatin included in their therapeutic regimens. The neurotoxic effects were more serious among the cisplatin-treated subjects. Four percent of the cisplatin-treated patients experienced severe neurotoxicity in the form of a walking disability. The results indicate that about half of all ovarian cancer patients treated with cisplatin may be expected to develop neurotoxic effects, and that the proportion of neurotoxic effects will probably reach 60 percent among the long-term survivors. The only factor found to positively correlate with the likelihood of neurotoxicity is the dose of cisplatin. (Consumer Summary produced by Reliance Medical Information, Inc.)

Evaluation, Ovarian cancer

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Survival of diffuse large cell lymphoma: a multivariate analysis including dose intensity variables

Article Abstract:

While many factors, such as patient age, play important roles as prognostic indicators in treatment for cancer, chemotherapeutic dose is one of the few that can actually be changed by the oncologist. The effect of chemotherapeutic dosage on survival in 95 cases of a non-Hodgkin's lymphoma (diffuse large-cell lymphoma) was evaluated by calculating the average relative dose intensity. The dose intensity of a drug is calculated by dividing the total dose by the amount of time over which the dose is delivered. The relative dose intensity is the proportion of the specified protocol dosage that is actually delivered to the patient, since treatment is often altered as a result of the changing condition of the patient. In the present study, the average relative dose intensities of cyclophosphamide, doxorubicin, and vincristine were 0.9, 0.86, and 0.79, respectively. The average relative dose intensity is simply the average of the individual intensities of these three drugs for each patient. When the Cox proportional hazards method was used to determine the factors that significantly contribute to the outcomes of the cases, it was found that age over 60 years and average relative dose intensity were significant prognostic factors. This was true both when all patients were considered and when patients achieving complete responses were considered separately. That is, patients who achieved a complete response to chemotherapy were more likely to relapse and die if the dose intensity of the therapy that induced the response was less than the median intensity. The results indicate that deviation from protocol dosage can have profound effects on survival. However, the difficulties in comparing the chemotherapeutic regimens reported in different studies remain, and the means by which the most effective dose ranges may be evaluated is still uncertain. (Consumer Summary produced by Reliance Medical Information, Inc.)

Non-Hodgkin's lymphomas, Dosage and administration, Lymphomas

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Cisplatin-induced peripheral neuropathy: frequent off-therapy deterioration, demyelinating syndromes, and muscle cramps

Article Abstract:

The powerful chemotherapeutic agent cisplatin has several serious side effects, including sensory nerve neuropathy. Little is known, however, about either the extent of nerve damage or the degree to which recovery is possible. Since cisplatin is often used in the treatment of cancers that are potentially curable, serious side effects do not necessarily rule out its use, and it becomes extremely important to have reliable information concerning these side effects. While it might be generally thought that the deterioration of sensory nerves would stop when the cisplatin treatment is discontinued, evidence is accumulating that this is not necessarily the case. In a study of 45 patients treated with cisplatin for a variety of tumors, in 14 cases sensory nerve deterioration continued for 2.5 to 5.5 months after chemotherapy was discontinued. Only four patients showed some signs of improvement during follow-up. Muscle cramps and signs of nerve demyelination presaged symptomatic deterioration among the patients. However, even the asymptomatic patients were found to have signs of neurological damage upon careful examination. Furthermore, in eight patients, signs of demyelination developed during cisplatin administration, but did not progress despite continued chemotherapy. No clinical feature could be identified to distinguish patients whose sensory function deteriorated after chemotherapy from those whose sensory nerves did not deteriorate. The results confirm that cisplatin is toxic to peripheral sensory nerves, and perhaps motor nerves as well. While all patients receiving cisplatin chemotherapy should be neurologically evaluated, the identification of peripheral neuropathy does not mean that the chemotherapy should necessarily be suspended. (Consumer Summary produced by Reliance Medical Information, Inc.)

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