Results of phase I clinical trials of Coramsine in patients with advanced solid tumors

2070 Background: Coramsine (C) is a 1:1 mixture of solasonine and solamargine, plant glycoalkaloids found in the species Solanum Linneanum, with single agent and synergistic combination in vitro and in vivo preclinical efficacy in various tumor models through interaction with rhamnose-containing cell membrane glycoproteins and subsequent internalization. Methods: C initially as a 2-hr IV infusion daily × 5 every 2 weeks to define the MTD, recommended Phase II dose, toxicity and pharmacokinetics. Based on preclinical toxicology the infusion duration was increased to 4 hours and 24 hours (120 hr continuous infusion). Doses studied range from 0.75 mg/kg/day to 3.0 mg/kg/day. Results: 27 pts were treated. DLT occurred in 2/2 pts at 1.5 mg/kg/day (2 hr) and 2/2 pts each at 3.0 mg/kg/day (4 hr and 24 hr). Preceding dose levels 1.0 mg/kg (2 hr) and 1.5 mg/kg (4 hr) produced DLT in 2/6 pts each with no grade IV. Over 24 hr, 2.25 mg/kg/day produced DLT in 4/6 patients. Limiting toxicity at all schedules was grade ...