nsc-141537 and Colonic-Neoplasms

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

Anguidine is a fungal metabolite with antitumor activity in a murine colon cancer model. Because of disappointing results in clinical trials, we analyzed the lethal and cytokinetic effects of anguidine on cultured human colon cancer cells. The studies revealed a moderate reduction in survival only after prolonged drug exposure. Continuous incubation with anguidine for longer than 48 hr produced a moderate increase in the percentage of S-phase cells and a slight decrease in the proportion of cells in G1/0, by pulse cytophotometry. An immediate reduction in the cumulative labeling index for cells continuously exposed to tritiated thymidine and anguidine and a rapid decrease in the cumulative mitotic index for cells continuously exposed to Colcemid and anguidine indicated a block at the G1 into S and G2 into mitosis transitions. Tumoricidal activity of anguidine in a cultured human colon cancer line is poor and requires prolonged exposure. The kinetic data reflect an almost frozen state of the cell cycle.

Topics: Adenocarcinoma; Cell Cycle; Cell Line; Cell Survival; Colonic Neoplasms; Humans; Kinetics; Neoplasms, Experimental; 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