Phase I evaluation of anguidine (diacetoxyscirpenol, NSC-141537)

A toxicologic evaluation of anguidine (diacetoxyscirpenol) was completed for a 5 day schedule. At 4.5 mg/M2 and 6 mg/M2 iv push CNS symptoms and hypotension were dose limiting but only mild to moderate myelosuppression was observed. At the 6 mg/M2 dose level on a 5 day schedule given by 8 hour infusion, myelosuppression was unacceptable while other toxic manifestations were minimal. An infusion of 4.5 mg/M2 over 4-8 hours appears to be an acceptable compromise between CNS, cardiovascular, and GI toxicity and myelosuppression. For patients with liver dysfunction or prior nitrosourea therapy, the starting dose should be 3.0 mg/M2.