Initial clinical experience with a simultaneous combination of 2,4-diamino-5(3',4'-dichlorophenyl)-6-methylpyrimidine (DDMP) with folinic acid.
DDMP, a diaminopyrimidine folate antagonist, was given to 26 tumor patients in a dosage of 50 mg/m2 per week orally, simultaneously with 3 mg CF i.m. or i.v. The CF dose was increased to 30 mg in patients showing evidence of toxicity, and withdrawn in the absence of toxicity. The dose-limiting toxicity was seen in myelosuppression, particularly thrombopenia and skin rashes. At the 3 mg CF level, 18 out of 26 patients developed toxicity. No toxicity was seen at the 30 mg CF level in 11 patients. After cessation of CF, toxicity occurred in five out of seven patients. After the onset of toxicity, CF was added as a delayed rescue, in a dosage of 15 mg every 8 h or 30-60 mg daily. One patient died of sepsis with agranulocytosis. All other patients recovered from myelosuppression within 1 or 2 weeks. Objective responses were observed in seven patients, four of the ten with epidermoid cancer of the head and neck, two out of eight with epidermoid cancer of the lung, and one out of three with melanoma.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011739:Pyrimethamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000970:Antineoplastic Agents; C006308:metoprine; D002955:Leucovorin; D011739:Pyrimethamine