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.

Elliptinium Acetate in Metastatic Breast Cancer – a Phase II Study

“…Elliptinium has significant activity in a variety of mu rine tumors, including L-1210 and P-388 leukemias, Lewis lung carcinoma, Gardner's lymphosarcoma, and B-16 melanoma. In European phase II studies in metastatic breast cancer, 27-37% of the patients showed objective response with elliptinium acetate [2][3][4][5], In a phase I study done at our institute, a few patients with breast cancer were included in the trial, and the objective responses were observed in the phase I study [6], Based on these observations, elliptinium was evaluated in patients with metastatic breast can cer in a phase II study.…”

“…Elliptinium (2 N-methyl-9-hydroxyellipticine) is a fully synthesized member of naturally occurring plant alkaloids, ellipticines [1][2][3]. Elliptinium has a high affinity for DNA, intercalating between base pairs.…”