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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 4/2018

Open Access 01-10-2018 | Original Article

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

Authors: Richard Greil, Sigrun Greil-Ressler, Lukas Weiss, Charlotte Schönlieb, Teresa Magnes, Bianca Radl, Gordon T. Bolger, Brigitta Vcelar, Peter P. Sordillo

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2018

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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.
Literature
1.
Khor TO, Keum YS, Lin W, Kim JH, Hu R, Shen G et al (2006) Combined inhibitory effects of curcumin and phenethyl isothiocyanate on the growth of human PC-3 prostate xenografts in immunodeficient mice. Cancer Res 66:613–621CrossRefPubMed
2.
Meskin MS, Bidlack WR, Davies AJ, Lewis DS, Randolph RK (2003) Phytochemicals: mechanisms of action. CRC Press, Boca RatonCrossRef
3.
Chainani-Wu N (2003) Safety and anti-inflammatory activity of curcumin: a component of turmeric (Curcuma longa). J Altern Complement Med 9:161–168CrossRefPubMed
4.
Di Pierro F, Settembre R (2013) Safety and efficacy of an add-on therapy with curcumin phytosome and piperine and/or lipoic acid in subjects with a diagnosis of peripheral neuropathy treated with dexibuprofen. J Pain Res 6:497–503CrossRefPubMedPubMedCentral
5.
Kanai M, Otsuka Y, Otsuka K, Sato M, Nishimura T, Mori Y et al (2013) A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin®) in cancer patients. Cancer Chemother Pharmacol 71:1521–1530CrossRefPubMed
6.
Kunwar A, Barik A, Mishra B, Rathinasamy K, Pandey R, Priyadarsini KI (2008) Quantitative cellular uptake, localization and cytotoxicity of curcumin in normal and tumor cells. Biochim Biophys Acta Gen Subj 1780:673–679CrossRef
7.
Bolger GT, Licollari A, Tan A, Greil R, Pleyer L, Vcelar B, Majeed M, Sordillo P (2018) Distribution of curcumin and THC in peripheral blood mononuclear cells isolated from healthy individuals and patients with chronic lymphocytic leukemia. Anticancer Res 38:121–130PubMed
8.
Sordillo PP, Helson L (2015) Curcumin and cancer stem cells: curcumin has asymmetrical effects on cancer and normal stem cells. Anticancer Res 35:599–614PubMed
9.
Chen F, Wang H, Xiang X, Yuan J, Chu W, Xue X et al (2014) Curcumin increased the differentiation rate of neurons in neural stem cells via wnt signaling in vitro study. J Surg Res 192:298–304CrossRefPubMed
10.
Tiwari SK, Agarwal S, Seth B, Yadav A, Nair S, Bhatnagar P et al (2013) Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in Alzheimer’s disease model via canonical Wnt/β-catenin pathway. ACS Nano 8:76–103CrossRefPubMed
11.
Chang YC, Chang WC, Hung KH, Yang DM, Cheng YH, Liao YW et al (2014) The generation of induced pluripotent stem cells for macular degeneration as a drug screening platform: identification of curcumin as a protective agent for retinal pigment epithelial cells against oxidative stress. Front Aging Neurosci 6:191CrossRefPubMedPubMedCentral
12.
Aziza SA, Abdel-Aal SA, Mady HA (2014) Chemopreventive effect of curcumin on oxidative stress, antioxidant status, DNA fragmentation and caspase-9 gene expression in 1, 2-dimethylhydrazine-induced colon cancer in rats. Am J Biochem Mol Biol 4:22–34CrossRef
13.
Hua WM, Liang ZQ, Fang Y, Gu ZL, Guo CY (2009) Mechanisms of curcumin protecting endothelial cells against ischemia and reperfusion injury. Chin Pharmacol Bull 8:13
14.
Han J, Pan XY, Xu Y, Xiao Y, An Y, Tie L et al (2012) Curcumin induces autophagy to protect vascular endothelial cell survival from oxidative stress damage. Autophagy 8:812–825CrossRefPubMed
15.
Xu Y, Ku B, Cui L, Li X, Barish PA, Foster TC (2007) Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats. Brain Res 1162:9–18CrossRefPubMed
16.
Wang YJ, Pan MH, Cheng AL, Lin LI, Ho YS, Hsieh CY et al (1997) Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal 15:1867–1876CrossRefPubMed
17.
Sharma RA, Steward WP, Gescher AJ (2007) Pharmacokinetics and pharmacodynamics of curcumin. In: Aggarwal BB, Surh Y, Shishodia S (eds) The molecular targets and therapeutic uses of curcumin in health and disease. Springer, Boston, pp 453–470CrossRef
18.
Li L, Braiteh FS, Kurzrock R (2005) Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis. Cancer 104:1322–1331CrossRefPubMed
19.
Li L, Ahmed B, Mehta K, Kurzrock R (2007) Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer. Mol Cancer Ther 6:1276–1282CrossRefPubMed
20.
Mach CM, Mathew L, Mosley SA, Kurzrock R, Smith JA (2009) Determination of minimum effective dose and optimal dosing schedule for liposomal curcumin in a xenograft human pancreatic cancer model. Anticancer Res 29:1895–1899PubMed
21.
Helson L, Bolger G, Majeed M, Vcelar B, Pucaj K, Matabudul D (2012) Infusion pharmacokinetics of Lipocurc™(liposomal curcumin) and its metabolite tetrahydrocurcumin in Beagle dogs. Anticancer Res 32:4365–4370PubMed
22.
Ranjan AP, Mukerjee A, Helson L, Gupta R, Vishwanatha JK (2013) Efficacy of liposomal curcumin in a human pancreatic tumor xenograft model: inhibition of tumor growth and angiogenesis. Anticancer Res 33:3603–3609PubMed
23.
Storka A, Vcelar B, Klickovic U, Gouya G, Weisshaar S, Aschauer S et al (2015) Safety, tolerability and pharmacokinetics of liposomal curcumin (Lipocurc™) in healthy humans. Int J Clin Pharmacol Ther 53:54–65CrossRefPubMed
24.
Matabudul D, Pucaj K, Bolger G, Vcelar B, Majeed M, Helson L (2012) Tissue distribution of (Lipocurc™) liposomal curcumin and tetrahydrocurcumin following two-and eight-hour infusions in beagle dogs. Anticancer Res 32:4359–4364PubMed
25.
Manrique-Moreno M, Villena F, Sotomayor CP, Edwards AM, Muñoz MA, Garidel P et al (2011) Human cells and cell membrane molecular models are affected in vitro by the nonsteroidal anti-inflammatory drug ibuprofen. Biochim Biophys Acta Biomembr 1808:2656–2664CrossRef
26.
Pierce A, Nester T (2011) Pathology consultation on drug-induced hemolytic anemia. Am J Clin Pathol 136:7–12CrossRefPubMed
27.
28.
Barbaryan A, Iyinagoro C, Nwankwo N, Ali AM, Saba R, Kwatra SG et al (2013) Ibuprofen-induced hemolytic anemia. Case Rep Hematol 142865:1–3
29.
Storka A, Vcelar B, Klickovic U, Gouya G, Weisshaar S, Aschauer S et al (2013) Effect of liposomal curcumin on red blood cells in vitro. Anticancer Res 33:3629–3634PubMed
30.
Vareed SK, Kakarala M, Ruffin MT, Crowell JA, Normolle DP, Djuric Z et al (2008) Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomark Prev 17:1411–1417CrossRef
31.
Pan M-H, Huang T-M, Lin J-K (1999) Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos 27:486–494PubMed
32.
Sordillo LA, Sordillo PP, Helson L (2016) Sphingosine kinase inhibitors as maintenance therapy of glioblastoma after ceramide-induced response. Anticancer Res 36:2085–2095PubMed
Metadata
Title
A phase 1 dose-escalation study on the safety, tolerability and activity of liposomal curcumin (Lipocurc™) in patients with locally advanced or metastatic cancer
Authors
Richard Greil
Sigrun Greil-Ressler
Lukas Weiss
Charlotte Schönlieb
Teresa Magnes
Bianca Radl
Gordon T. Bolger
Brigitta Vcelar
Peter P. Sordillo
Publication date
01-10-2018
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2018
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-018-3654-0

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