Clinical and pharmacologic evaluation of split-dose intermittent therapy with dianhydrogalactitol

Dianhydrogalactitol was administered as two 1-hr infusions separated by a 4-hr period once every 5 weeks to 21 patients with advanced solid tumors. Total doses ranged from 100 mg/m2 (50 mg/m2 twice on a single day) to 160 mg/m2 (80 mg/m2 twice on a single day). Peak concentrations of drug at the end of a 1-hr infusion ranged from 1.9 to 5.6 microgram/ml. Plasma elimination of dianhydrogalactitol was approximated best by a two-compartment open model. The alpha-half-life was 3.9 +/- 1.9 mins and the beta-half-life was 31.3 +/- 2.7 mins. Dose-limiting hematologic toxicity was encountered at a total dose of 160 mg/m2, with leukopenia occurring more frequently than thrombocytopenia. Other toxic effects included mild to moderate nausea in most patients and two instances of moderate alopecia. One patient with large cell cancer of the lung had a partial regression lasting 2 months and one patient with a carcinoid in the thymus had a partial regression lasting 7 1/2 months. A third patient with a mixed adenocarcinoma-squamous cell carcinoma of the lung had improvement (30% decrease) in his pulmonary tumor for greater than 2 months.