Indicine-N-oxide: a new antitumor agent

Indicine-N-oxide, a pyrrolizidine derivative, was selected for development because of activity in the murine P388 leukemia model. Route and schedule dependency have been demonstrated. It is believed that the antitumor activity of the drug is mediated via antimitotic effects and chromosomal damage. However, the active metabolic species responsible for these antitumor properties is not yet known. The major toxic effect was myelosuppression. Phase I clinical trials have arrived at recommended doses for further study. Colon carcinoma has been found to be possibly responsive, and several tumor types were reported stable during phase I testing. In a single phase II study in refractory leukemia, there were three responses, including one complete response, among seven patients. Phase II studies in all panel tumors are indicated, especially colon carcinoma and leukemias.