PMID: 3770040Jul 1, 1986Paper

Altered pharmacokinetics and clinical consequences of low dose methotrexate plus cisplatin in the treatment of advanced head and neck cancer

European Journal of Cancer & Clinical Oncology
G A MilanoF Demard

Abstract

Thirty-two patients with head and neck carcinoma received a multidrug chemotherapy protocol including low dose methotrexate (LDMTX) (30 mg/m2) and cisplatin as their initial treatment. A sensitive immunoenzymatic technique was used for systematic MTX blood monitoring (0-56 hr) in all patients. The MTX-related side effects observed in 15 patients (47%) were significantly associated with an increase in systemic drug exposure occurring early during drug infusion. The average end-of-infusion concentration varied from 8 X 10(-7) M for nontoxic patients to 1.45 and 3.12 10(-6) M for moderately and severely toxic patients respectively. The area under the curve (AUC) (0-56 hr) was also directly related to the increase in side-effects. Total body clearance was reduced in an inverse manner. Volumes of distribution and terminal elimination half-lives were not related to the presence or intensity of MTX side-effects. Based on these data, the institution of folinic acid rescue adapted to the MTX blood concentration, a measure previously not suggested for LDMTX, completely prevented severe toxicity in a subsequent series of 26 patients without modification of the response rate.

References

Jan 1, 1985·Cancer Chemotherapy and Pharmacology·A L StewartS B Lucas
Jan 13, 1983·The New England Journal of Medicine·W K Hong, R Bromer
May 1, 1983·Clinical Pharmacokinetics·F M BalisW A Bleyer
Jan 1, 1984·Cancer Chemotherapy and Pharmacology·N HaimE Robinson
Feb 21, 1981·British Medical Journal·R L WoodsM H Tattersall
Jan 1, 1983·Cancer Chemotherapy and Pharmacology·G MilanoC M Lalanne

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Citations

Jun 13, 1998·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M C EtienneG Milano
Feb 7, 2003·Fundamental & Clinical Pharmacology·Annick Rousseau, Pierre Marquet

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