Phase I study of 5-azacytidine (NSC-102816) using 24-hour continuous infusion for 5 days

The biologic and antitumor activity of 5-azacytidine has been well demonstrated in the past. The drug at present is thought to be primarily cell cycle phase specific. This study was designed to eliminate undesirable side effects (mainly nausea and vomiting) occurring with a bolus dose and to confirm the recent findings of the relative stability of 5-azacytidine's solution with preserved biologic and antitumor activity. In the study we determined that a dose of 150 mg/m2/day given as a 120-hour continuous iv infusion and repeated at 28-day intervals produced safe, manageable, and reproducible toxicity. The drug was freshly prepared at 4-hour intervals. Eleven courses were administered to seven patients at this dose level and no patient experienced nausea or vomiting. Leukopenia was the major toxic effect. Antitumor activity was shown in one patient with colon cancer and another with American Burkitt's lymphoma.