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Pharmacol Res. 2018 Jun;132:72-79. doi: 10.1016/j.phrs.2018.03.013. Epub 2018 Mar 31.

Phytosome complex of curcumin as complementary therapy of advanced pancreatic cancer improves safety and efficacy of gemcitabine: Results of a prospective phase II trial.

Author information

1
Rare Tumors Unit, Veneto Institute of Oncology IOV - IRCCS, Via Gattamelata 64, 35128 Padua (PD), Italy; Department of Oncology, S. Maria del Prato Hospital, Via Bagnols sur Ceze 3, 3203 Feltre (BL), Italy. Electronic address: davide.pastorelli@aulss1.veneto.it.
2
Regional Center for Biomarkers, Department of Clinical Pathology and Transfusion Medicine, Azienda ULSS 3 Serenissima, Regional Hospital, Campo SS Giovanni e Paolo 6777, 30122 Venice (VE), Italy. Electronic address: aline.fabricio@aulss3.veneto.it.
3
Department of Oncology, S. Maria del Prato Hospital, Via Bagnols sur Ceze 3, 3203 Feltre (BL), Italy. Electronic address: petros.giovanis@aulss1.veneto.it.
4
Department of Oncology, S. Maria del Prato Hospital, Via Bagnols sur Ceze 3, 3203 Feltre (BL), Italy. Electronic address: sd.simonadippolito@gmail.com.
5
Clinical Trials and Biostatistics Unit, Veneto Institute of Oncology IOV - IRCCS, Via Gattamelata 64, 35128 Padua (PD), Italy. Electronic address: pasquale.fiduccia@iov.veneto.it.
6
Medical Oncology Azienda ULSS 3 Serenissima, Ospedale dell'Angelo, Via Paccagnella 11, 30174 Mestre (VE), Italy. Electronic address: caterina.solda@aulss3.veneto.it.
7
Gastroenterology Unit, S. Maria del Prato Hospital, Via Bagnols sur Ceze 3, 32032 Feltre (BL), Italy. Electronic address: andrea.buda@aulss1.veneto.it.
8
Department of Surgery, Oncological and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35128 Padua (PD), Italy. Electronic address: cosimo.sperti@unipd.it.
9
Department of Surgery, Oncological and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35128 Padua (PD), Italy. Electronic address: romeo.bardini@unipd.it.
10
Department of Surgery, Oncological and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35128 Padua (PD), Italy. Electronic address: gianfranco.dadalt@aopd.veneto.it.
11
Veneto Institute of Oncology IOV - IRCCS, Via Gattamelata 64, 35128 Padua (PD), Italy. Electronic address: giulia.rainato@gmail.com.
12
Regional Center for Biomarkers, Department of Clinical Pathology and Transfusion Medicine, Azienda ULSS 3 Serenissima, Regional Hospital, Campo SS Giovanni e Paolo 6777, 30122 Venice (VE), Italy. Electronic address: massimo.gion@aulss3.veneto.it.
13
Department of Molecular Medicine, University of Padua, Viale C. Colombo, 3, 35121 Padua (PD), Italy. Electronic address: fulvio.ursini@unipd.it.

Abstract

A large body of biomedical evidence indicates that activation of Nrf2 by curcumin increases the nucleophilic tone and damps inflammation cumulatively supporting the malignant phenotype. Conversely, genetic analyses suggest a possible oncogenic nature of constitutive Nrf2 activation since an increased nucleophilic tone is alleged increasing chemoresistance of cancer cells. Aiming to contribute to solve this paradox, this study addressed the issue of safety and efficacy of curcumin as complementary therapy of gemcitabine on pancreatic cancer. This was a single centre, single arm prospective phase II trial. Patients received gemcitabine and Meriva®, a patented preparation of curcumin complexed with phospholipids. Primary endpoint was response rate, secondary endpoints were progression free survival, overall survival, tolerability and quality of life. Analysis of inflammatory biomarkers was also carried out. Fifty-two consecutive patients were enrolled. Forty-four (13 locally advanced and 31 metastatic) were suitable for primary endpoint evaluation. Median age was 66 years (range 42-87); 42 patients had Eastern Cooperative Oncology Group performance status 0-1. The median number of treatment cycle was 4.5 (range 2-14). We observed 27.3% of response rate and 34.1% of cases with stable disease, totalizing a disease control rate of 61.4%. The median progression free survival and overall survival were 8.4 and 10.2 months, respectively. Higher IL-6 and sCD40L levels before treatment were associated to a worse overall survival (p < 0.01). Increases in sCD40L levels after 1 cycle of chemotherapy were associated with a reduced response to the therapy. Grade 3/4 toxicity was observed (neutropenia, 38.6%; anemia, 6.8%). There were no significant changes in quality of life during therapy. In conclusion, the complementary therapy to gemcitabine with phytosome complex of curcumin is not only safe but also efficiently translate in a good response rate in first line therapy of advanced pancreatic cancer.

KEYWORDS:

Biomarker; Curcumin; Gemcitabine; Pancreatic cancer; Phase II trial; Response rate

PMID:
29614381
DOI:
10.1016/j.phrs.2018.03.013
[Indexed for MEDLINE]

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