Initial clinical study with pyrazofurin.
Twenty-five patients with inoperable carcinoma and lymphoma were given pyrazofurin (pf) by iv bolus at a dose level ranging from 100 to 300 mg/m2 of estimated body surface area. In addition, five patients with acute leukemia were given PF by infusion at doses ranging from 250 mg/m2/24 hours to 1500 mg/m2/144 hours. PF was well tolerated by most patients at doses of 100 mg/m2 given as an iv bolus weekly or 250 mg/m2 given every 2-3 weeks. However, an infusion of 750 mg/m2 given over a period of 72-120 hours to leukemic patients resulted in severe but reversible toxicity; 1500 mg/m2 of PF given over a 144-hour period to one patient resulted in the development of severe mucocutaneous toxicity and leukopenia. The patient died of hemorrhagic pneumonitis. The major toxic effects observed were mucosal (oral pain, cheilosis, redness, and oral and lip ulcers), cutaneous (erythema, erosion, and bullae), and hematologic (anemia, leukopenia, and thrombocytopenia). The mucosal manifestations appear to be the dose-limiting toxic factors in most patients. Toxic reactions were more pronounced in patients who had previously received radiotherapy; dose-limiting hematologic toxic reactions occurred in four. After treatment with PF, one of the four patients with breast carcinoma had a partial response (greater than 50% regression) lasting 5 weeks. Another patient with breast carcinoma improved for about 1 month.[1]References
- Initial clinical study with pyrazofurin. Ohnuma, T., Holland, J.F. Cancer treatment reports. (1977) [Pubmed]
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