A phase 1 dose-escalation study on the safety, tolerability and activity of liposomal curcumin (Lipocurc(™)) in patients with locally advanced or metastatic cancer

PURPOSE: This study was conducted to investigate the safety and tolerability of increasing doses of liposomal curcumin in patients with metastatic cancer. Investigations of anti-tumor activity and of the pharmacokinetics of curcumin were secondary objectives. METHODS: In this phase I, single-center, open-label study in patients with metastatic tumors, liposomal curcumin was administered as a weekly intravenous infusion for 8 weeks. Dose escalation was started at 100 mg/m(2) over 8 h and the dose increased to 300 mg/m(2) over 6 h. RESULTS: 32 patients were treated. No dose-limiting toxicity was observed in 26 patients at doses between 100 and 300 mg/m(2) over 8 h. Of six patients receiving 300 mg/m(2) over 6 h, one patient developed hemolysis, and three other patients experienced hemoglobin decreases > 2 g/dL without signs of hemolysis. Pharmacokinetic analyses revealed stable curcumin plasma concentrations during infusion followed by rapid declines to undetectable levels after the infusion. Anti-tumor activity by RECIST V1.1 was not detected. Significant tumor marker responses and transient clinical benefit were observed in two patients. CONCLUSION: 300 mg/m(2) liposomal curcumin over 6 h was the maximum tolerated dose in these heavily pretreated patients, and is the recommended starting dose for anti-cancer trials.