Phase I Study of Elliptinium (2-N-Methyl-9-Hydroxyellipticinium)

Abstract

Elliptinium (2-N-methyl-9-hydroxyellipticinium), a chemotherapeutic agent whose mechanism of action has not been completely elucidated, intercalates into DNA. In this Phase I clinical trial, the schedule of drug administration consisted of weekly intravenous infusions. Twenty-nine patients were evaluable for toxicity. The initial dose level was 40 mg/m² and was escalated to 150 mg/m² through six levels. The dose-limiting side effects were emesis, xerostomia, and azotemia. The lack of myelosuppression was the most striking feature. Objective responses (partial remission, minor response) were seen in one patient each with Hodgkin's disease, non-Hodgkin's lymphoma, breast cancer, and nasopharyngeal carcinoma. We recommend a Phase II evaluation of elliptinium at a dose of 100 mg/m² on a weekly schedule.