Sequential combination of pyrazofurin and 5-azacytidine in patients with acute myelocytic leukemia and carcinoma.
The combination of pyrazofurin (PF) and 5-azacytidine (5-aza-CR) was evaluated in 12 patients with neoplastic diseases who had failed conventional therapies. They included 6 patients with acute myelocytic leukemia (AML) and 6 with various carcinomas. PF was given by i.v. bolus at doses ranging from 25 to 200 mg/m2 followed by 5-aza-CR given by continuous 24-hour infusion at doses ranging from 30 to 120 mg/m2/24 h during 40-ic diseases who had failed conventional therapies. They included 6 patients with acute myelocytic leukemia (AML) and 6 with various carcinomas. PF was given by i.v. bolus at doses ranging from 25 to 200 mg/m2 followed by 5-aza-CR given by continuous 24-hour infusion at doses ranging from 30 to 120 mg/m2/24 h during 40-ic diseases who had failed conventional therapies. They included 6 patients with acute myelocytic leukemia (AML) and 6 with various carcinomas. PF was given by i.v. bolus at doses ranging from 25 to 200 mg/m2 followed by 5-aza-CR given by continuous 24-hour infusion at doses ranging from 30 to 120 mg/m2/24 h during 40--120 h. Dose-limiting toxicity was mucocutaneous, which appeared in 11/17 courses. Skin rash was similar to that produced by PF alone, but was present after much lower doses of PF when followed by 5-aza-CR. Moderate and reversible thrombocytopenia and leukopenia occurred in 3/6 patients with carcinoma. No objective response was seen in patients with carcinoma, and no marrow remission occurred in patients with AML. 24-Hour urinary excretion of orotidine and oroticacid were measured during 11 courses in 8 patients, and were not much different than those obtained previously with PF alone. The occurrence of mucocutaneous toxicity precluded the use of higher doses of PF and 5-aza-CR, which might have been therapeutically more active.
D000230:Adenocarcinoma / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000577:Amides; D001374:Azacitidine / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles; D012263:Ribonucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D012266:Ribose
D000577:Amides; D011720:Pyrazoles; D012263:Ribonucleosides; C002997:pyrazofurin; D012266:Ribose; D001374:Azacitidine