PMID: 6970753Apr 1, 1981Paper

Long-duration intracavitary infusion of methotrexate with systemic leucovorin protection in patients with malignant effusions

The Journal of Clinical Investigation
S B HowellJ Mendelsohn

Abstract

18 patients with malignant effusions were treated with continuous intraperitoneal, intrapleural, or intrapericardial infusion of methotrexate (MTX) 30 mg/m2 per d combined with simultaneous intravenous administration of leucovorin at a dose rate calculated to yield an equimolar concentration in the serum. In the serum the geometric mean steady-state MTX concentration was 0.95 microM, whereas it was 24 microM in the peritoneal, 213 microM in the pleural, and 434 microM in the pericardial cavities. Mean clearance was 6.6 ml/min from the peritoneal cavity, 2.6 ml/min from the pleural cavity, and 0.14 ml/min from the pericardial cavity. Leucovorin provided sufficient protection to allow the duration of infusion to be escalated from 24 to 120 h before myelosuppression was encountered. Marrow thymidylate synthetase activity was inhibited by an average of 46% compared to 86% inhibition in malignant cells in the effusions. Flow cytometric analysis showed no perturbation of the cell cycle phase distribution of marrow cells. All eight of the evaluable patients have responded: three received no other form of therapy, five also received systemic hormonal or chemotherapy. This study demonstrated that tumors confined to third space body flui...Continue Reading

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Citations

Jan 1, 1990·Cancer Chemotherapy and Pharmacology·P Y HoloyeR A Newman
Mar 1, 1987·Current Problems in Cancer·R F Ozols, R C Young
Jan 1, 1984·Cancer Drug Delivery·M MarkmanM R Green
Jan 1, 1985·Cancer Drug Delivery·H J Keizer, H M Pinedo
Jan 1, 1985·Cancer Drug Delivery·M MarkmanW E Lucas
Jan 1, 1986·Cancer Drug Delivery·S B Howell, C E Pfeifle
Apr 11, 2008·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·S B Howell
Jan 1, 1983·Cancer Investigation·C E Myers, J M Collins
Mar 1, 1986·The American Journal of the Medical Sciences·M Markman
Mar 1, 1987·European Journal of Cancer & Clinical Oncology·H S Hochster, M Piccart
Jan 1, 1990·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·G Los, J G McVie
Mar 1, 1983·Cancer Treatment Reviews·J H Schornagel, J G McVie
Aug 1, 1986·Current Problems in Cancer·M Markman
Nov 22, 2012·Asian Pacific Journal of Cancer Prevention : APJCP·Jin-Yu HuangHui-Mian Xu
Apr 22, 2000·Cancer Treatment Reviews·L S HofstraP H Willemse
Oct 15, 1988·Cancer·K R GeisingerH D Homesley
Jul 1, 1986·European Journal of Cancer & Clinical Oncology·P CanalH Roche

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