Phase I trial of Indicine-N-Oxide on two dose schedules

Indicine-N-Oxide is the water soluble N-oxide of the pyrolizidine alkaloid indicine recently evaluated in Phase I trials. Initially in a weekly times four schedule, twenty-nine patients were treated with a dose range of 1.0 to 7.5 g/m2 per week. Fifteen of 40 of the courses of four doses were interrupted by myelosuppression which prohibited completion of the course. Therefore, an intermittent schedule was evaluated utilizing single doses repeated every 3-4 weeks. Twenty-six patients were treated at doses of 5 to 10 g/m2. Myelosuppression is the dose limiting toxicity of both schedules with thrombocytopenia being more severe than leukopenia. Myelosuppression is predictable and reversible on the intermittent schedule. It is more severe in patients with heavy prior treatment. Partial responses were seen in four patients, one with a mucoepidermoid carcinoma of the salivary gland and three with adenocarcinoma of the colon. Phase II studies are planned at a starting dose of 7.5 g/m2 every 3-4 weeks in patients with no prior treatment and 5 g/m2 in patients with prior treatment.