nsc-141537 and Hypotension

Thirty-three patients with advanced colorectal adenocarcinoma were treated with daily Anguidine i.v. 5 mg/m2 X 5 for 3 weeks. The patients were stratified into two groups: prior chemotherapy and no prior chemotherapy. No responses were noted. Major toxicities were hypotension and fever.

Topics: Antineoplastic Agents, Phytogenic; Colonic Neoplasms; Drug Evaluation; Fever; Humans; Hypotension; Rectal Neoplasms; Sesquiterpenes; Trichothecenes

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.

Topics: Bone Marrow; Central Nervous System; Digestive System; Drug Evaluation; Humans; Hypotension; Infusions, Parenteral; Injections, Intravenous; Liver Neoplasms; Mycotoxins; Neoplasms; Sesquiterpenes; Trichothecenes

Anguidine was administered in a dose of 5.0 mg/m2 (3.5 mg/m2 for patients with hepatic dysfunction) intravenously daily for 5 days in a phase II evaluation of 19 patients with metastatic adenocarcinoma of the colon or rectum. Courses were repeated every 3 weeks. No responses were observed but five patients had disease stabilization. Toxicity was marked, causing discontinuation of therapy in several patients. Anguidine appears ineffective in patients with metastatic colon or rectal cancer in the dose and schedule used in this study.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Bone Marrow; Colonic Neoplasms; Drug Evaluation; Female; Fever; Humans; Hypotension; Male; Middle Aged; Rectal Neoplasms; Sesquiterpenes; Trichothecenes