Cisplatin and Methotrexate
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The risk of fatal methotrexate toxictty appears to be markedly increased by previous treatment with cisplatin.
Six out of 106 patients died with clinical signs of methotrexate toxicity 6-13 days after receiving 20-50 mg/m2 in the absence of the usual signs of renal dysfunction and despite having previously been treated with methotrexate without serious toxicity All had had prior treatment with cisplatin Four of the patients were regarded as good-risk. A study in children and adolescents suggested that the cumulative dose of asplatin received appears to increase the risk of methotrexate toxicity. Another study indicated that the sequential use of cisplatin and high-dose methotrexate was nephrotoxic and decreased the amount of methotrexate which could be given. A report on 14 patients on high dose methotrexate indicated that prior treatment with one course of cisplatin sharply increased their serum levels of methotrexate, and after two courses the increase was even more marked (an eightfold rise).
The picture is not totally clear but it seems possible that prior treatment with cisplatin causes kidney damage which may not necessarily be detectable with the usual creatinine clearance tests The effect is to cause a marked reduction in the clearance of the methotrexate The serum methotrexate levels of these patients should be closely monitored so that any delay in its clearance is detected early and appropriate measures taken.
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