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.[1]References
- Sequential combination of pyrazofurin and 5-azacytidine in patients with acute myelocytic leukemia and carcinoma. Chahinian, A.P., Ohnuma, T., Greenfield, D.S., Holland, J.F. Oncology (1981) [Pubmed]
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