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

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.