Chloroquinoxoline sulfonamide is a halogenated heterocyclic sulfanilamide that demonstrated antineoplastic activity in the human tumor stem cell clonogenic assay. Since this agent is not related to previously known families of chemotherapeutic agents, it is a particularly interesting compound for study. Earlier clinical studies using bolus administration were limited by dose-limiting hypoglycemia. Since hypoglycemia appeared to be related to peak level rather than overall exposure, we proposed this Phase I study using a 7-day continuous infusion to attempt to ameliorate this toxicity while maintaining full dose treatment. Pharmacokinetics of the infusional regimen were also studied, and serial glucose measurements were compared to matched determinations of serum insulin level. The study has now been completed. Doses as high as 4400 mg/m2 over 7 days were administered to 19 patients, with the maximum tolerated dose determined to be 3300 mg/m2. Derived pharmacokinetic parameters were consistent with those from other studies. Mild dose-related hypoglycemia with matched hyperinsulinemia was seen on Day 1 but was not dose-limiting and did not recur during the week-long infusion. The dose limiting toxicity was instead determined to be myelosuppression. Several patients achieved minor response or stabilization of disease. Discussions with NCI concerning the possibility of Phase II studies are continuing.
Showing the most recent 10 out of 94 publications
