Phase I and II studies of the decitabine–genistein drug combination in advanced solid tumors.

e13556 Background: The combination of epigenetic drug decitabine with genistein, a natural isoflavone, produces synergistic responses in preclinical studies with particular activity shown in lung cancer cell lines. Our phase I dose-escalation study of decitabine with a fixed dose of genistein to treat advanced solid tumor was followed by a phase II study in advanced lung cancer patients. Methods: In phase I, decitabine was administered over 10-hours at increasing doses (60, 120, 240 mg/m2) with continuous administration of genistein 300 mg/day orally. Treatment cycles were repeated every 4 to 6 weeks. The MTD was 120 mg/m2 with neutropenia as DLT. Decitabine at 120 mg/m2 and genistein produced plasma levels of 0.62±0.06 µM and 8.5±5.6 µM, respectively. Results: The drug combination was well tolerated and produced stable disease for more than 6 months (7-14 months) in 5/10 patients. One gastric cancer patient had a 50% reduction in tumor burden after 6 months of therapy. Stable disease was also achieved in...