A Phase II Trial of Oral Trimethylcolchicinic Acid in Patients with Hormone Refractory Prostate Cancer

Hormone refractory prostate cancer (HRPC) will affect more than 40,000 men in the United States in 1999, and only a few drugs have activity in this disease. We studied trimethylcolchicinic acid (TMCA), an oral colchicine derivative, in a Phase II trial involving 18 chemotherapy-naive men with HRPC. TMCA, 5 mg/m2/day, was given orally for 4 or 5 days with cycles repeated every 3 weeks. No patients showed an objective response by clinical or prostate specific antigen criteria. Neutropenia and stomatitis were common on this schedule. One fatal episode of neutropenic fever occurred. Pharmacokinetics suggested drug accumulation on Days 4 and 5. The cumulative area under the curve (AUC) of concentration × time correlated with the log neutrophil nadir, the log platelet nadir, and the severity of stomatitis. We conclude that TMCA has no clinical effect on HRPC despite severe hematologic toxicity and stomatitis, and that its hematologic toxicity is related to the AUC.