Intraveneus curcumine in combinatie met chemo (paclitaxel) bij borstkankerpatienten met uitgezaaide borstkanker geeft betere respons (plus 23 procent) en lichamelijk welbevinden in vergelijking met een placebo na 12 weken chemokuren copy 1

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Overall, treatment with curcumin in combination with paclitaxel was superior to the paclitaxel-placebo combination with respect to ORR and physical performance after 12 weeks of treatment. Intravenously administered curcumin caused no major safety issues and no reduction in quality of life, and it may be beneficial in reducing fatigue.

https://doi.org/10.1016/j.phymed.2020.153218 Get rights and content

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Highlights

•: This is the first clinical study to explore the efficacy and safety of administering curcumin intravenously in combination with chemotherapy in the treatment of cancer patients.

Abstract

Background

: The clinical efficacy of curcumin has not yet been established for the treatment of cancer, despite a large body of evidence from numerous preclinical studies suggesting the therapeutic potential of curcumin, particularly in a synergistic combination with paclitaxel. The main obstacle in using curcumin for adjunctive cancer therapy is its low bioavailability via oral administration.

Purpose

: We assessed the efficacy and safety of intravenous curcumin infusion in combination with paclitaxel in patients with metastatic and advanced breast cancer.

Study Design

: A randomized, double-blind, placebo-controlled, parallel-group comparative clinical study was conducted.

Methods

: A total of 150 women with advanced and metastatic breast cancer were randomly assigned to receive either paclitaxel (80 mg/m2) plus placebo or paclitaxel plus curcumin (CUC-1®, 300 mg solution, once per week) intravenously for 12 weeks with 3 months of follow-up. The primary outcome was determined based on the objective response rate (ORR), as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). The secondary outcomes were progression-free survival (PFS), time to tumor progression (TTP), time to tumor treatment failure (TTTF), safety, and quality of life.

Results

: The intention-to-treat (ITT) analysis revealed that the ORR of curcumin was significantly higher than that of the placebo (51% vs. 33%, p < 0.01) at 4 weeks of follow-up. The difference between the groups was even greater when only patients who had completed the treatment (61% vs. 38%, odds ratio ==2.64, p < 0.01) were included. A superior effect of curcumin vs placebo was observed in both patients who had completed the treatment and all patients included in the ITT analysis, 3 months after termination of the treatment. No other significant differences were observed between the curcumin and the placebo groups, except for fatigue (3 vs. 10 patients, respectively; odds ratio ==3.7, p = 0.05). However, the patients’ self-assessed overall physical performance was significantly higher with curcumin than the placebo during the treatment and at the end of the follow-up, suggesting better tolerance in the curcumin group.

Conclusions

: Overall, treatment with curcumin in combination with paclitaxel was superior to the paclitaxel-placebo combination with respect to ORR and physical performance after 12 weeks of treatment. Intravenously administered curcumin caused no major safety issues and no reduction in quality of life, and it may be beneficial in reducing fatigue.

Advances in knowledge

: This is the first clinical study to explore the efficacy and safety of administering curcumin intravenously in combination with chemotherapy in the treatment of cancer patients.

Graphical abstract

Intravenous administration of curcumin in combination with paclitaxel was superior to that of the paclitaxel-placebo combination with respect to ORR and physical performance after 12 weeks of treatment in patients with advanced and metastatic breast cancer. Intravenous administration of curcumin yielded no major safety concerns and no reduction in the quality of life but may be beneficial in reducing fatigue.

References

Abouzeid et al., 2014a: A.H. Abouzeid, N.R. Patel, C. Sarisozen, V.P. TorchilinTransferrin-targeted polymeric micelles co-loaded with curcumin and paclitaxel: efficient killing of paclitaxel-resistant cancer cells

Pharm Res, 31 (2014), pp. 1938-1945

CrossRef View Record in Scopus Google Scholar
Abouzeid et al., 2014b: A.H. Abouzeid, N.R. Patel, V.P. TorchilinPolyethylene glycol-phosphatidylethanolamine (PEG-PE)/vitamin E micelles for co-delivery of paclitaxel and curcumin to overcome multi-drug resistance in ovarian cancer

Int J Pharm, 464 (2014), pp. 178-184

Article Download PDF View Record in Scopus Google Scholar
Aggarwal et al., 2013: B.B. Aggarwal, S.C. Gupta, B. SungCurcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers

Br J Pharmacol, 169 (2013), pp. 1672-1692

CrossRef View Record in Scopus Google Scholar
Aggarwal et al., 2005: B.B. Aggarwal, S. Shishodia, Y. Takada, S. Banerjee, R.A. Newman, C.E. Bueso-Ramos, JE. PriceCurcumin suppresses the paclitaxel-induced nuclear factor-kappa pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice

Clin Cancer Res., 11 (2005), pp. 7490-7498

CrossRef View Record in Scopus Google Scholar
Alemi et al., 2018: A. Alemi, Zavar Reza, Haghiralsadat J., Zarei Jaliani F., Haghi Karamallah M. H., S.A. Hosseini, S. Haghi KaramallahPaclitaxel and curcumin coadministration in novel cationic PEGylated niosomal formulations exhibit enhanced synergistic antitumor efficacy

J Nanobiotechnology, 16 (2018), p. 28, 10.1186/s12951-018-0351-4

Google Scholar
Anand et al., 2007: P. Anand, A.B. Kunnumakkara, R.A. Newman, B.B. AggarwalBioavailability of curcumin: problems and promises

Molecular Pharmaceutics, 4 (2007), pp. 807-818

CrossRef View Record in Scopus Google Scholar
Bava et al., 2011: S.V. Bava, C.N. Sreekanth, A.K.T. Thulasidasan, N.P. Anto, V.T. Cheriyan, V.T. Puliyappadamba, S.G. Menon, S.D. Ravichandran, R.J. AntoAkt is upstream and MAPKs are downstream of NF-kappa B in paclitaxel-induced survival signaling events, which are down-regulated by curcumin contributing to their synergism

Int. J. Biochem. Cell Biol., 43 (2011), pp. 331-341

Article Download PDF View Record in Scopus Google Scholar
Bharti and Aggarwal, 2002: A.C. Bharti, B.B. AggarwalNuclear factor-kappa B and cancer: its role in prevention and therapy

BiochemPharmacol, 64 (2002), pp. 883-888

Article Download PDF View Record in Scopus Google Scholar
Boztas et al., 2013: A.O. Boztas, O. Karakuzu, G. Galante, Z. Ugur, F. Kocabas, C.Z. Altuntas, A.O. YazaydinSynergistic interaction of paclitaxel and curcumin with cyclodextrin polymercomplexation in human cancer cells

Mol Pharm, 10 (2013), pp. 2676-2683

CrossRef View Record in Scopus Google Scholar
Calaf et al., 2018: G.M. Calaf, R. Ponce-Cusi, F. CarriónCurcumin and paclitaxel induce cell deathin breast cancer cell lines

Oncol Rep, 40 (2018), pp. 2381-2388

View Record in Scopus Google Scholar
Campbell and Collett, 2005: F.C. Campbell, G.P. CollettChemopreventive properties of curcumin

Future Oncol, 1 (2005), pp. 405-414

CrossRef View Record in Scopus Google Scholar
Cardoso et al., 2014: F. Cardoso, A. Costa, L. Norton, E. Senkus, M. Aapro, F. André, C.H. Barrios, J. Bergh, L., Biganzoli, K.L. Blackwell, M.J. Cardoso, T. Cufer, N. El Saghir, L. Fallowfield, D. Fenech, P. Francis, K. Gelmon, S.H. Giordano, J. Gligorov, A. Goldhirsch, N. Harbeck, N. Houssami, C. Hudis, B. Kaufman, I. Krop, S. Kyriakides, U.N. Lin, M. Mayer, S.D. Merjaver, E.B. Nordström, O. Pagani, A. Partridge, F. Penault-Llorca, M.J. Piccart, H. Rugo, G. Sledge, C. Thomssen, L. Van't Veer, D. Vorobiof, C. Vrieling, N. West, B. Xu, E. WinerESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2) dagger

Ann Oncol, 25 (2014), pp. 1871-1888

Article Download PDF CrossRef View Record in Scopus Google Scholar
Chen et al., 2014: B. Chen, Y. Zhang, Y. Wang, J. Rao, X. Jiang, Z. XuCurcumin inhibits proliferation of breast cancer cells through Nrf2-mediated down-regulation of Fen1 expression

J Steroid Biochem Mol Biol, 143 (2014), pp. 11-18

Article Download PDF View Record in Scopus Google Scholar
Cheng et al., 2001: A.L. Cheng, C.H. Hsu, J.K. Lin, M.M. Hsu, Y.F. Ho, T.S. Shen, J.Y. Ko, J.T. Lin, B.R. Lin, W. Ming-Shiang, H.S. Yu, S.H. Jee, G.S. Chen, T.M. Chen, C.A. Chen, M.K. Lai, Y.S. Pu, M.H. Pan, Y.J. Wang, C.C. TsaiPhase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions

Anticancer Res, 21 (2001), pp. 2895-2900

Google Scholar
Chia et al., 2007: S.K. Chia, C.H. Speers, Y. D'Yachkova, A. Kang, S. Malfair-Taylor, J. Barnett, A. Coldman, K.A. Gelmon, S.E. O'Reilly, I.A. OlivottoThe impact of new chemotherapeuticand hormone agents on survival in a population-based cohort of women withmetastatic breast cancer

Cancer, 110 (2007), pp. 973-979

CrossRef View Record in Scopus Google Scholar
Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics. Guidance for Industry 2007: Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics. Guidance for Industry2007. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER). pp. 1-19.
Google Scholar
Curcuma Longa 2002: Curcuma LongaIndian Herbal Pharmacopoeia, Revised new edition

Indian Drug Manufacturers Association, Mumbai (2002), pp. 169-180

Google Scholar
Curcumae Longae Rhizoma 2010: Curcumae Longae RhizomaPharmacopoeia of the People's Republic of China

(English ed. X) (2010), pp. 139-140

Google Scholar
Decker et al., 2017: T Decker, F. Overkamp, S. Rösel, A. Nusch, T. Göhler, M. Indorf, J. Sahlmann, T. TrarbachA randomized phase II study of paclitaxel alone versus paclitaxel plus sorafenib in second- and third-line treatment of patients with HER2-negative metastatic breast cancer (PASO)

BMC Cancer, 17 (1) (2017), p. 499, 10.1186/s12885-017-3492-1

doi: ker

Google Scholar
Devassy et al., 2015: J.G. Devassy, I.D. Nwachukwu, P.J. JonesCurcumin and cancer: barriers to obtaininga health claim

Nutr Rev, 73 (2015), pp. 155-165

CrossRef View Record in Scopus Google Scholar
Di Leo et al., 2008: A. Di Leo, H.L. Gomez, Z. Aziz, Z. Zvirbule, J. Bines, M.C. Arbushites, S.F. Guerrera, M. Koehler, C. Oliva, S.H. Stein, L.S. Williams, J. Dering, R.S. Finn, M.F. PressPhase III, double-blind, randomized study comparing lapatinib plus paclitaxel with placebo plus paclitaxel as first-line treatment for metastatic breast cancer

J Clin Oncol, 26 (2008), pp. 5544-5552, 10.1200/JCO.2008.16.2578

View Record in Scopus Google Scholar
Duvoix et al., 2005: A. Duvoix, R. Blasius, S. Delhalle, M. Schnekenburger, F. Morceau, E. Henry, M. Dicato, M. DiederichChemopreventive and therapeutic effects of curcumin

Cancer Lett, 223 (2005), pp. 181-190

Article Download PDF View Record in Scopus Google Scholar
Duvoix et al., 2005: A. Duvoix, R. Blasius, S. Delhalle, M. Schnekenburger, F. Morceau, E. Henry, M. Dicato, M. DiederichChemopreventive and therapeutic effects of curcumin

Cancer Lett, 223 (2005), pp. 181-190

Article Download PDF View Record in Scopus Google Scholar
Eisenhauera et al., 2009: E.A. Eisenhauera, P. Therasse, J. Bogaerts, L.H. Schwartz, D. Sargent, R. Ford, J. Dancey, S. Arbuck, S. Gwyther, M. Mooney, L. Rubinstein, L. Shankar, L. Dodd, R. Kaplan, D. Lacombe, J. VerweijNew response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)

Eur J Cancer., 45 (2009), pp. 228-247

Google Scholar
FDA 2017: FDAAn FDA Investigation into Two Serious Adverse Events Associated with ImprimisRx's Compounded Curcumin Emulsion Product for Injection

FDA (2017)

8 August 2017

https://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/pharmacycompounding/ucm570192.htm

Google Scholar
Fruijtier-Pölloth, 2005: C. Fruijtier-PöllothSafety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products

Toxicology, 214 (2005), pp. 1-38

Article Download PDF View Record in Scopus Google Scholar
Ganta and Amiji, 2009: S. Ganta, M. AmijiCoadministration of Paclitaxel and curcumin in nanoemulsionformulations to overcome multidrug resistance in tumor cells

Mol Pharm, 26 (2009), pp. 928-939

CrossRef View Record in Scopus Google Scholar
Gradishar et al., 2013: W.J. Gradishar, V. Kaklamani, T.P. Sahoo, D. Lokanatha, V. Raina, S. Bondarde, M. Jain, S.K. Ro, N.A. Lokker, L. SchwartzbergA double-blind, randomised, placebocontrolled,phase 2b study evaluating sorafenib in combination with paclitaxelas a first-line therapy in patients with HER2-negative advanced breast cancer

Eur J Cancer, 49 (2013), pp. 312-322

Article Download PDF View Record in Scopus Google Scholar
Hesari et al., 2019: A. Hesari, M. Azizian, A. Sheikhi, A. Nesaei, S. Sanaei, N. Mahinparvar, M. Derakhshani, P. Hedayt, F. Ghasemi, H. MirzaeiChemopreventive and therapeutic potential of curcumin in esophageal cancer: Current and future status

Int J Cancer, 144 (2019), pp. 1215-1226

CrossRef View Record in Scopus Google Scholar
Huang et al., 2011: H.C. Huang, C.L. Lin, J.K. Lin1,2,3,4,6-penta-O-galloyl-β-D-glucose, quercetin, curcumin and lycopene induce cell-cycle arrest in MDA-MB-231 and BT474 cells through downregulation of Skp2 protein

J Agric Food Chem, 59 (2011), pp. 6765-6775

CrossRef View Record in Scopus Google Scholar
Jang et al., 2001: S.H. Jang, M.G. Wientjes, J.L. AuKinetics of P-glycoprotein-mediated efflux of paclitaxel

J. Pharmacol. Exp. Ther., 298 (2001), pp. 1236-1242

View Record in Scopus Google Scholar
Johnson and Mukhtar, 2007: J.J. Johnson, H. MukhtarCurcumin for chemoprevention of colon cancer

Cancer Lett, 255 (2007), pp. 170-181

Article Download PDF View Record in Scopus Google Scholar
Kang et al., 2009: H.J. Kang, S.H. Lee, J.E. Price, L.S. KimCurcumin suppresses the paclitaxel-induced nuclear factor-kappaB in breast cancer cells and potentiates the growth inhibitory effect of paclitaxel in a breast cancer nude mice model

Breast J, 15 (2009), pp. 223-229

CrossRef View Record in Scopus Google Scholar
Karnofsky and Burchenal, 1949: D. Karnofsky, J. BurchenalThe clinical evaluation of chemotherapeutic agents in cancer

C. MacLeod (Ed.), Evaluation of Chemotherapeutic Agents, Columbia University Press, New York (1949), pp. 191-205

View Record in Scopus Google Scholar
Kim et al., 2001: M.S. Kim, H.J. Kang, A. MoonInhibition of invasion and induction of apoptosis by curcumin in H-ras-transformed MCF10A human breast epithelial cells

Arch Pharm Res, 24 (2001), pp. 349-354

View Record in Scopus Google Scholar
Kizhakkayil et al., 2010: J. Kizhakkayil, F. Thayyullathil, S. Chathoth, A. Hago, M. Patel, S. GaladariModulation of curcumin-induced Akt phosphorylation and apoptosis by PI3K inhibitor in MCF-7 cells

BiochemBiophys Res Commun, 394 (2010), pp. 476-481

Article Download PDF View Record in Scopus Google Scholar
Kumar et al., 2015: P. Kumar, A. Kadakol, P.K. Shasthrula, N.A. Mundhe, V.S. Jamdade, C.C. Barua, A.B. GaikwadCurcumin as an adjuvant to breast cancer treatment

Anticancer Agents Med Chem, 15 (2015), pp. 647-656

CrossRef View Record in Scopus Google Scholar
Kunnumakkara et al., 2008: A.B. Kunnumakkara, P. Anand, B.B. AggarwalCurcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interactionwith multiple cell signaling proteins

Cancer Lett, 269 (2008), pp. 199-225

Article Download PDF View Record in Scopus Google Scholar
Lasoff et al., 2018: D.R. Lasoff, F.L. Cantrell, B.T. LyDeath associated with intravenous turmeric (Curcumin) preparation

Clin Toxicol (Phila), 56 (2018), pp. 384-385

CrossRef View Record in Scopus Google Scholar
Li et al., 2014: X. Li, W. Xie, C. Xie, C. Huang, J. Zhu, Z. Liang, F. Deng, M. Zhu, W. Zhu, R. Wu, J. Wu, S. Geng, C.. ZhongCurcumin modulates miR-19/PTEN/AKT/p53 axis to suppress bisphenol A-induced MCF-7 breast cancer cell proliferation

Phytother Res, 28 (2014), pp. 1553-1560

View Record in Scopus Google Scholar
Lin et al., 2012: L. Lin, P. Wang, X.L. ZhaoStudy on curcumin-induced apoptosis in ovarian cancer resistant cell lines COC1/DDP

Sichuan Da XueXue Bao Yi Xue Ban, 43 (2012), pp. 335-339

Chinese. PubMed PMID: 22812232

View Record in Scopus Google Scholar
Liu and Chen, 2013: D. Liu, Z. ChenThe effect of curcumin on breast cancer cells

J Breast Cancer, 16 (2013), pp. 133-137

CrossRef View Record in Scopus Google Scholar
Lowe and Lin, 2000: S.W. Lowe, A.W. LinApoptosis in cancer

Carcinogenesis, 21 (2000), pp. 485-495

View Record in Scopus Google Scholar
Lv et al., 2014: Z.D. Lv, X.P. Liu, W.J. Zhao, Q. Dong, F.N. Li, H.B. Wang, B. KongCurcumin induces apoptosis in breast cancer cells and inhibits tumor growth in vitro and in vivo

Int J Clin Exp Pathol, 7 (2014), pp. 2818-2824

View Record in Scopus Google Scholar
Menon and Sudheer, 2007: V.P. Menon, A.R. SudheerAntioxidant and anti-inflammatory properties of curcumin

Adv Exp Med Biol, 595 (2007), pp. 105-125

CrossRef View Record in Scopus Google Scholar
Park and Conteas, 2010: J. Park, C.N. ConteasAnti-carcinogenic properties of curcumin on colorectal cancer

World J Gastrointest Oncol, 2 (2010), pp. 169-176

View Record in Scopus Google Scholar
Quispe-Soto and Calaf, 2016: E.T. Quispe-Soto, G.M. CalafEffect of curcumin and paclitaxel on breast carcinogenesis

Int J Oncol, 49 (2016), pp. 2569-2577

CrossRef View Record in Scopus Google Scholar
Rhizoma Curcumae Longae 1999: Rhizoma Curcumae Longae, in: WHO monographs on selected medicinal plants. — World Health Organization. 1999, Vol. 1, 115-124.
Google Scholar
Rose, 2014: Rose, U-B., 2014. PharmazeutischeFormulierungenhaltened Curcumin,Patent DE 10 2012 2019 291 A1, 2014.05.28.
Google Scholar
Sharma et al., 2004: R.A. Sharma, S.A. Euden, S.L. Platton, D.N. Cooke, A. Shafayat, H.R. Hewitt, T.H. Marczylo, B. Morgan, D. Hemingway, S.M. Plummer, M. Pirmohamed, A.J. Gescher, W.P. StewardPhase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance

Clin Cancer Res, 10 (2004), pp. 6847-6854

CrossRef View Record in Scopus Google Scholar
Sharma et al., 2007: R.A. Sharma, W.P. Steward, A.J. GescherPharmacokinetics and pharmacodynamics of curcumin

Adv Exp Med Biol, 595 (2007), pp. 453-470

CrossRef View Record in Scopus Google Scholar
Sreekanth et al., 2011: C.N. Sreekanth, S.V. Bava, E. Sreekumar, R.J. AntoMolecular evidences for the chemosensitizing efficacy of liposomal curcumin in paclitaxel chemotherapy in mouse models of cervical cancer

Oncogene, 30 (2011), pp. 3139-3152

CrossRef View Record in Scopus Google Scholar
Storka et al., 2015: A. Storka, B. Vcelar, U. Klickovic, G. Gouya, S. Weisshaar, S. Aschauer, G. Bolger, L. Helson, M. WolztSafety, tolerability and pharmacokinetics of liposomalcurcumin in healthy humans

Int J Clin Pharmacol Ther., 53 (1) (2015), pp. 54-65

CrossRef View Record in Scopus Google Scholar
Sugimura et al., 2004: M. Sugimura, S. Sagae, S. Ishioka, Y. Nishioka, K. Tsukada, R. KudoMechanisms of paclitaxel-induced apoptosis in an ovarian cancer cell line and its paclitaxel-resistant clone

Oncology, 66 (2004), pp. 53-61

View Record in Scopus Google Scholar
Vareed et al., 2008: S.K. Vareed, M. Kakarala, M.T. Ruffin, J.A. Crowell, D.P. Normolle, Z. Djuric, D.E. BrennerPharmacokinetics of curcumin conjugate metabolites in healthy human subjects

Cancer Epidemiol Biomarkers Prev, 17 (2008), pp. 1411-1417

CrossRef View Record in Scopus Google Scholar
Wei et al., 2017: Y. Wei, X. Pu, L. ZhaoPreclinical studies for the combination of paclitaxel andcurcumin in cancer therapy (Review)

Oncol Rep, 37 (2017), pp. 3159-3166

CrossRef View Record in Scopus Google Scholar
Zhan et al., 2014: Y. Zhan, Y. Chen, R. Liu, H. Zhang, Y. ZhangPotentiation of paclitaxel activity by curcumin in human breast cancer cell by modulating apoptosis and inhibiting EGFR signaling

Arch Pharm Res, 37 (2014), pp. 1086-1095

CrossRef View Record in Scopus Google Scholar