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

Cancer Chemother Pharmacol. 2018 Oct;82(4):695-706. doi: 10.1007/s00280-018-3654-0. Epub 2018 Aug 3.

Abstract

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/m2 over 8 h and the dose increased to 300 mg/m2 over 6 h.

Results: 32 patients were treated. No dose-limiting toxicity was observed in 26 patients at doses between 100 and 300 mg/m2 over 8 h. Of six patients receiving 300 mg/m2 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/m2 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.

Keywords: Colon carcinoma; Curcumin; Hemolysis; Lipocurc; Phase I cancer trials; Prostate carcinoma.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Colonic Neoplasms* / drug therapy
  • Colonic Neoplasms* / pathology
  • Curcumin* / administration & dosage
  • Curcumin* / adverse effects
  • Curcumin* / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Drug Monitoring / methods
  • Drug Tolerance
  • Drug-Related Side Effects and Adverse Reactions* / blood
  • Drug-Related Side Effects and Adverse Reactions* / diagnosis
  • Drug-Related Side Effects and Adverse Reactions* / etiology
  • Female
  • Hemoglobins / analysis
  • Hemolysis / drug effects
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Metastasis / pathology
  • Neoplasm Staging
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / pathology
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Hemoglobins
  • Curcumin