Summary
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bleyer WA (1978) The clinical pharmacology of methotrexate. Cancer 41: 36–51
Chabner BA, Donehower RC, Schilsky RL (1981) Clinical pharmacology of methotrexate. Cancer Treat Rep [Suppl 1] 65: 51–54
Dentino M, Luft FC, Yum MN, Williams SD, Einhorn CH (1978) Long-term effects of cis-diamminedichloride platinum (CDDP) on renal function and structure in man. Cancer 41: 1274–1281
Djerassi I, Kim JS, Nayak N, Dhanissian H, Adler S, Hsieh S (1977) New “rescue” with massive doses of citrovorum factor for potentially lethal methotrexate toxicity. Cancer Treat Rep 61: 749–750
Greenspan EM (1975) Clinical cancer chemotherapy. Raven Press, New York, p 49
Keefe DA, Capizzi RL, Rudnick SA (1982) Methotrexate cytotoxicity for L5178Y/Asn lymphoblasts: relationship of dose and duration of exposure to tumor cell viability. Cancer Res 42: 1641–1645
Mandel MA (1976) The synergistic effect of salicylates on methotrexate toxicity. Plast Reconstr Surg 57: 733–737
Murphy WK, Valdivieso M, Bodey GP et al (1980) cis-dichlorodiammine platinum-II (DDP), methotrexate (MTX) and bleomycin (BLM) chemotherapy for patients with advanced squamous cell carcinoma of the head and neck. Proc AACR/ASCO 21: 166
Pitman SW, Mino DR, Papac R et al. (1979) Sequential methotrexate-leucovorin (MTX-LCV) and cis-platinum (CDDP) in head and neck cancer. Proc AACR/ASCO 20: 419
Von Hoff DD, Penta JS, Helman LJ, Slavik M (1977) Incidence of drug-related deaths secondary to high-dose methotrexate and citrovorum factor administration. Cancer Treat Rep 61: 745–748
Zaharko DS (1974) Pharmacokinetics and drug effect. Biochem Pharmacol [Suppl 2] 23: 1–8
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Haim, N., Kedar, A. & Robinson, E. Methotrexate-related deaths in patients previously treated with cis-diamminedichloride platinum. Cancer Chemother. Pharmacol. 13, 223–225 (1984). https://doi.org/10.1007/BF00269034
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00269034