Multicenter randomized phase II study comparing docetaxel plus curcumin versus docetaxel plus placebo in first‐line treatment of metastatic castration‐resistant prostate cancer

Passildas, Judith; Eymard, Jean‐Christophe; Pouget, Mélanie; Kwiatkowski, Fabrice; Praagh, Isabelle Van; Savareux, L.; Atger, Marc; Durando, Xavier; Abrial, Catherine; Richard, Damien; Ginzac, Angeline; Thivat, Émilie; Monange, Brigitte; Chollet, Philippe; Mahammedi, Hakim

doi:10.1002/cam4.3806

Cited by 41 publications

(36 citation statements)

References 28 publications

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“…Abundant evidence indicates a potent role of phytochemicals in both -mitochondrial health quality support on the one hand and on the other hand significantly enhanced response of cancer cells towards anti-cancer therapies including radiotherapy and chemotherapy; also an evident mitigation of negative side-effects frequently observed for conventional anti-cancer therapies have been reported [21][22][23][24][25][26].…”

Section: Plant-based Anti-cancer Interventionthe General Viewmentioning

confidence: 99%

“…However, current clinical evidence on the effects of phytochemical in palliative PCa care is lacking. The search on medical database provided only the evidence of phytochemicals affecting the adverse events associated with conventional PCa treatment modalities [22][23][24][25][26] -therefore potentially improving the quality of life during therapy.…”

Section: Milk Thistle (Silibinin)mentioning

confidence: 99%

“…The study evaluating the combination of docetaxel, prednisone, and curcumin in patients with castration-resistant PCa described good tolerability and patient acceptability [22]. However, a recent study by Passildas-Jahanmohan et al ( 2021) observed no effects of adding curcumin to treatment strategies (docetaxel) for patients with castration-resistant PCa in improving patient outcome and prognosis [23]. On the contrary, lycopene plus docetaxel exerted favourable effects in metastatic castrate-resistant PCa patients.…”

Section: B Stimulating Effects Of Phytochemicals On Anti-cancer Chemo...mentioning

confidence: 99%

“…By evaluating randomly selected clinical trials (29 studies in total), almost 70% were identified as demonstrating positive effects of phytosubstances in reducing risks of PCa progression such as listed by references [35,76]. Moreover, several studies included in our review highlighted supportive and stimulating effects of conventional anti-cancer therapy as well as an evident mitigation of their adverse effects [21][22][23][24][25][26].…”

Section: Secondary Carementioning

confidence: 99%

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Anti-prostate cancer protection and therapy in the framework of predictive, preventive and personalised medicine — comprehensive effects of phytochemicals in primary, secondary and tertiary care

et al. 2022

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According to the GLOBOCAN 2020, prostate cancer (PCa) is the most often diagnosed male cancer in 112 countries and the leading cancer-related death in 48 countries. Moreover, PCa incidence permanently increases in adolescents and young adults. Also, the rates of metastasising PCa continuously grow up in young populations. Corresponding socio-economic burden is enormous: PCa treatment costs increase more rapidly than for any other cancer. In order to reverse current trends in exploding PCa cases and treatment costs, pragmatic decisions should be made, in favour of advanced populational screening programmes and effective anti-PCa protection at the level of the health-to-disease transition (sub-optimal health conditions) demonstrating the highest cost-efficacy of treatments. For doing this, the paradigm change from reactive treatments of the clinically manifested PCa to the predictive approach and personalised prevention is essential.Phytochemicals are associated with potent anti-cancer activity targeting each stage of carcinogenesis including cell apoptosis and proliferation, cancer invasiveness and metastatic disease. For example, their positive effects are demonstrated for stabilising and restoring mitochondrial health quality, which if compromised is strongly associated with sub-optimal health conditions and strong predisposition to aggressive PCa sub-types. Further, phytochemicals significantly enhance response of cancer cells to anti-cancer therapies including radio- and chemotherapy. Evident plant-based mitigation of negative side-effects frequently observed for conventional anti-cancer therapies has been reported. Finally, dual anti-cancer and anti-viral effects of phytochemicals such as these of silibinin have been demonstrated as being highly relevant for improved PCa management at the level of secondary and tertiary care, for example, under pandemic conditions, since PCa-affected individuals per evidence are highly vulnerable towards COVID-19 infection.Here, we present a comprehensive data analysis towards clinically relevant anti-cancer effects of phytochemicals to be considered for personalised anti-PCa protection in primary care as well as for an advanced disease management at the level of secondary and tertiary care in the framework of predictive, preventive and personalised medicine.

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Section: Plant-based Anti-cancer Interventionthe General Viewmentioning

confidence: 99%

Section: Milk Thistle (Silibinin)mentioning

confidence: 99%

Section: B Stimulating Effects Of Phytochemicals On Anti-cancer Chemo...mentioning

confidence: 99%

Section: Secondary Carementioning

confidence: 99%

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Anti-prostate cancer protection and therapy in the framework of predictive, preventive and personalised medicine — comprehensive effects of phytochemicals in primary, secondary and tertiary care

et al. 2022

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“…Although distinct effects have been noted in in vitro approaches, and although curcumin supplementation might have beneficial effects on some parameters related to prostate diseases [ 13 ], the overall clinical potential remains unsatisfactory. In fact, a recent interim analysis clearly showed that adding curcumin to metastatic castration-resistant prostate cancer patients was not effective in terms of progression-free survival [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Growth, Proliferation and Metastasis of Prostate Cancer Cells Is Blocked by Low-Dose Curcumin in Combination with Light Irradiation

Rutz

Benchellal

Kassabra

et al. 2021

IJMS

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Although anti-cancer properties of the natural compound curcumin have been reported, low absorption and rapid metabolisation limit clinical use. The present study investigated whether irradiation with visible light may enhance the inhibitory effects of low-dosed curcumin on prostate cancer cell growth, proliferation, and metastasis in vitro. DU145 and PC3 cells were incubated with low-dosed curcumin (0.1–0.4 µg/mL) and subsequently irradiated with 1.65 J/cm2 visible light for 5 min. Controls remained untreated and/or non-irradiated. Cell growth, proliferation, apoptosis, adhesion, and chemotaxis were evaluated, as was cell cycle regulating protein expression (CDK, Cyclins), and integrins of the α- and β-family. Curcumin or light alone did not cause any significant effects on tumor growth, proliferation, or metastasis. However, curcumin combined with light irradiation significantly suppressed tumor growth, adhesion, and migration. Phosphorylation of CDK1 decreased and expression of the counter-receptors cyclin A and B was diminished. Integrin α and β subtypes were also reduced, compared to controls. Irradiation distinctly enhances the anti-tumor potential of curcumin in vitro and may hold promise in treating prostate cancer.

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A phase I study of docetaxel plus synthetic lycopene in metastatic prostate cancer patients

Lilly,

Wu,

et al. 2024

Clinical & Translational Med

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PurposeOur preclinical studies showed that lycopene enhanced the anti‐prostate cancer efficacy of docetaxel in animal models. A phase I trial (NCT0149519) was conducted to identify an optimum dose of synthetic lycopene in combination with docetaxel (and androgen blockade [androgen deprivation therapy, ADT]), and to evaluate its effect on the safety and pharmacokinetics of docetaxel in men with metastatic prostate cancer.MethodsSubjects were treated with 21‐day cycles of 75 mg/m2 docetaxel (and ADT), plus lycopene at 30, 90 or 150 mg/day. A Bayesian model averaging continual reassessment method was used to guide dose escalation. Pharmacokinetics of docetaxel and multiple correlative studies were carried out.ResultsTwenty‐four participants were enrolled, 18 in a dose escalation cohort to define the maximum tolerated dose (MTD), and six in a pharmacokinetic cohort. Docetaxel/ADT plus 150 mg/day synthetic lycopene resulted in dose‐limiting toxicity (pulmonary embolus) in one out of 12 participants with an estimated probability of .106 and thus was chosen as the MTD. Lycopene increased the AUCinf and Cmax of plasma docetaxel by 9.5% and 15.1%, respectively. Correlative studies showed dose‐related changes in circulating endothelial cells and vascular endothelial growth factor A, and reduction in insulin‐like growth factor 1R phosphorylation, associated with lycopene therapy.ConclusionsThe combination of docetaxel/ADT and synthetic lycopene has low toxicity and favourable pharmacokinetics. The effects of lycopene on biomarkers provide additional support for the toxicity‐dependent MTD definition.Highlights The maximum tolerated dose was identified as 150 mg/day of lycopene in combination with docetaxel/ADT for the treatment of metastatic prostate cancer patients. Small increases in plasma exposure to docetaxel were observed with lycopene co‐administration. Mechanistically significant effects were seen on angiogenesis and insulin‐like growth factor 1 signalling by lycopene co‐administration with docetaxel/ADT.

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Multicenter randomized phase II study comparing docetaxel plus curcumin versus docetaxel plus placebo in first‐line treatment of metastatic castration‐resistant prostate cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 41 publications

References 28 publications

Anti-prostate cancer protection and therapy in the framework of predictive, preventive and personalised medicine — comprehensive effects of phytochemicals in primary, secondary and tertiary care

Anti-prostate cancer protection and therapy in the framework of predictive, preventive and personalised medicine — comprehensive effects of phytochemicals in primary, secondary and tertiary care

Growth, Proliferation and Metastasis of Prostate Cancer Cells Is Blocked by Low-Dose Curcumin in Combination with Light Irradiation

A phase I study of docetaxel plus synthetic lycopene in metastatic prostate cancer patients

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