Phase I clinical evaluation of anguidine

Anguidine, one of a new class of agents derived from fungi, was given to 39 patients in a phase I study. The drug was administered by rapid iv infusion daily for 5 days at 2-week intervals, starting at a dose of 0.1 mg/m ²/day. At ≥2.4 mg/m ², this toxicity included nausea, vomiting, hypotension, central nervous system symptoms (including somnolence, confusion, and ataxia), diarrhea, chills and fever, generalized burning erythema, stomatitis, shortness of breath, moderate myelosuppression, and other toxicity of minor significance. An association of life-threatening toxicity with the presence of liver metastases or impairment of liver function was recognized at doses ≥ 5mg/m ². Subsequently, patients with known liver disease were initially given a lower dose. None of the 35 patients with solid tumors nor the four patients with acute leukemia had complete or partial remission, but only 15 patients were considered to have treatment at adequate dose levels. The recommended dosage for phase II trials is 3.0 mg/m ²/day for 5 days for patients with liver metastases or impairment of liver function and 5.0 mg/m ²/day for 5 days for patients with normal livers; courses should be given by rapid (30-60 minutes) i.v. infusion every 3 weeks. Close observation should be made of renal and liver functions and hematologic parameters. For the present, patients with cardiovascular instability, jaundice, or ileostomy should be excluded from study with this drug.