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Among 106 patients treated with conventional-dose methotrexate (MTX) following prior therapy with cis-diamminedichloride platinum (CDDP), six died with clinical manifestations of MTX toxicity. Death occurred 6-13 days after the administration of 20-50 mg/m2 MTX. Toxicity included severe stomatitis and myelosuppression, which appeared in all six patients, skin rash in five, and diarrhea in four. Renal failure appeared in five cases and hepatic toxicity in four. All these patients had received MTX earlier without developing any serious toxicity. At the time of the last MTX administration, all had normal blood counts and also normal kidney and liver function tests. Prior therapy with CDDP may be responsible for this relatively high incidence of MTX-related deaths.
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