Phase I Study of a Five-Day Intermittent Schedule for 1,2:5,6-Dianhydrogalactitol (NSC-132313)

Summary

Because 1,2: 5,6-dianhydrogalactitol (NSC-132313 (DAG; the main conversion reaction product of the treatment of dibromodulcitol by mild alkali or human serum) showed considerable antitumor activity in various mouse and rat tumor systems, a phase I study in 50 patients was conducted with five daily iv treatments repeated every 6 weeks. Thrombocytopenia was the dose-limiting toxicity. At a dose of 40 mg/m²/day for 5 days, the median platelet nadir was 31,000/mm³ and occurred on day 20; the platelet count returned to normal within 8 days. At the same dose, the median white blood cell (WBC) nadir was 2,300/mm³ also on day 20; the WBC count returned to normal within 7 days. Anemia, nausea, and vomiting were usually mild to moderate. No renal, hepatic, central nervous system, cardiac, or pulmonary toxicity was identified. Antitumor effects of DAG were observed in patients with renal, bladder, and small-cell lung cancers. An iv dose of 20–30 mg/m²/day for 5 consecutive days, repeated every 5–6 weeks, was recommended for phase II studies.