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Phase I clinical trial and pharmacology of 2,4-diamino-5-(3′,4′-dichlorophenyl)-6-methylpyrimidine (metoprine) (DDMP) and folinic acid (CF)

par De Jager, Robert ;Dupont, Daniel;Rodzynek, Jean-Jacques ;Dorlet, Colette ;Lagrange, Gaston
Référence Cancer chemotherapy and pharmacology, 6, 1, page (75-80)
Publication Publié, 1981-07

Article révisé par les pairs

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Résumé :

Escalating doses of DDMP (metoprine) (15-280 mg/m2) were administered as single oral doses 24 h before a fixed leucovorin (CF) rescue (15 mg IM every 6 h for 72 h). CNS toxicity was dose-limiting and cumulative when the drug was given more frequently than at 3-week intervals. DDMP has a very long half-life (150 h) and is extensively bound to serum proteins (88%). It diffuses into the CSF and concentrates in brain tumours and normal brain tissue (brainserum ratio 3.8-5.3). DDMP is a potentially useful drug against brain tumors. Tumor regressions were seen in two patients with epidermoid carcinomas. © 1981 Springer-Verlag.