Τόμος 4 (1986) – Τεύχος 2 – Άρθρο 5 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 4 (1986) – Issue 2 – Article 5 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

High Dose Methotrexate: Pharmacology and Clinical Use

Ν. TSAVARIS, D. TSIGALAKIS, A. LAFI, K. VONORTA, D. PAPAIOANNOU, N. KARVOUNIS, P. KARAGIAOURIS, A. KARABELIS, P. KOSMIDES

4: 43-50 (1986)

PHARMAKON-Press: Epitheorese Klin. Farmakol. Farmakokinet.

4: 43-50 (1986)

The use of high doses of methotrexate with citrovorum factor rescue has considerably improved the prognosis of some malignancies, such as osteosarcoma. Massive doses of methotrexate may lead to severe or even lethal toxicity. Safe administration of this regiment requires a wide spectrum of labora­tory tests as well as clinical supervision. Through pharmacologic research we better un­derstand the basic steps in the action of me­thotrexate, including its transport across cell membranes, its intracellular conversion, its si­tes of action. In this article we review the important new concepts of methotrexate action and our experience in the use of high doses of methotrexate clinically.

1. Kotz, R., Krisch, K., Lack, W.: Hochdosierte methotre­xate – Be handlung bei osteogenem sarkom. Arzneim. Forsch 30 (11): 1953 (1980)
2. Frei, Ε., Jaffe, N., Tatersall, M.H.N., Pitman, S., Parker, L.: New approaches to cancer chemotherapy with metho­trexate. N. Engl. J. Med. 292: 846 (1975)
3. Jeffrey, J.E., Silber, F.R., Grant, T.T., Mirra, J.M., Wei­senberg, T.H., Dorey, F.J.: Management of stage II Β osteogenic Sarcoma: Experience at the University of California Los Angeles. Cancer Treat. Symp. 3: 117 (1985)
4. Jϋrgens, Η., Rosen, G.: Kombinations – Chemotherapie beim osteogenen sarcom. Erfahrungen am memorial sloan – kettering cancer. Center. Klin. Padiat. 192: 123 (1980)
5. Rosenblatt, D.S., Whitehead, V.M., Vera, N., Pottier, A., Dupont, M., Vuchich, M.J.: Prolong inhibition of DNA synthesis associated with accumulation of methotrexate polyglutamates by cultured human cells. Mol. Pharmacol. 14: 1143 (1978)