Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial

Tannock, I.; Fizazi, Karim; Иванов, С. А.; Karlsson, Camilla; Fléchon, Aude; Skoneczna, Iwona; Orlandi, Francisco F.; Gravis, Gwénaëlle; Matveev, Vsevolod; Bavbek, Sevil; Gil, Thierry; Viana, Luciano L.; Arén, Osvaldo; Karyakin, Oleg; Elliott, Tony; Birtle, Alison; Magherini, E.; Hatteville, Laurence; Petrylak, Daniel; Tombal, Bertrand; Rosenthal, Mark

doi:10.1016/s1470-2045(13)70184-0

Cited by 260 publications

(168 citation statements)

References 25 publications

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“…Although bevacizumab has shown some promise with improved progression-free survival, no significant improvement in overall survival has been achieved even in combination therapies (reviewed by Small & Oh (2012) and Armstrong et al (2013)). A newer anti-angiogenesis agent derived from the extracellular domains of the VEGFR (aflibercept) in combination with docetaxel and prednisone also offered no improvement in overall survival (Tannock et al 2013). Yet given the comparative success of trials of newer agents that target VEGF signaling in other cancer types (Qi et al 2011, Grothey et al 2013, further studies are required of these agents in the PCa setting (Fig.…”

Section: Anti-vegf Signaling Therapies In the Clinical Management Of Pcamentioning

confidence: 99%

Regulation of vascular endothelial growth factor in prostate cancer

Brot¹,

Ntekim²,

Cardenas³

et al. 2015

Endocrine-Related Cancer

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Prostate cancer (PCa) is the most common malignancy affecting men in the western world. Although radical prostatectomy and radiation therapy can successfully treat PCa in the majority of patients, up to w30% will experience local recurrence or metastatic disease. Prostate carcinogenesis and progression is typically an androgen-dependent process. For this reason, therapies for recurrent PCa target androgen biosynthesis and androgen receptor function. Such androgen deprivation therapies (ADT) are effective initially, but the duration of response is typically %24 months. Although ADT and taxane-based chemotherapy have delivered survival benefits, metastatic PCa remains incurable. Therefore, it is essential to establish the cellular and molecular mechanisms that enable localized PCas to invade and disseminate. It has long been accepted that metastases require angiogenesis. In the present review, we examine the essential role for angiogenesis in PCa metastases, and we focus in particular on the current understanding of the regulation of vascular endothelial growth factor (VEGF) in localized and metastatic PCa. We highlight recent advances in understanding the role of VEGF in regulating the interaction of cancer cells with tumor-associated immune cells during the metastatic process of PCa. We summarize the established mechanisms of transcriptional and post-transcriptional regulation of VEGF in PCa cells and outline the molecular insights obtained from preclinical animal models of PCa. Finally, we summarize the current state of anti-angiogenesis therapies for PCa and consider how existing therapies impact VEGF signaling.

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Section: Anti-vegf Signaling Therapies In the Clinical Management Of Pcamentioning

confidence: 99%

Regulation of vascular endothelial growth factor in prostate cancer

Brot¹,

Ntekim²,

Cardenas³

et al. 2015

Endocrine-Related Cancer

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“…Photothermal therapy (PTT) or radiotherapy has been combined with chemotherapy to enhance anticancer efficacy of chemotherapy in a synergistic manner. [7][8][9] Among various combination therapies, the combination of PTT with chemotherapy has showed a superior treatment effect in case of prostate cancer. 10,11 PTT usually utilizes near-infrared (NIR) lightabsorbing photosensitizers to damage tumor cells with laser irradiation by heating.…”

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confidence: 99%

Self-assembled albumin nanoparticles for combination therapy in prostate cancer

Lian

et al. 2017

IJN

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Resistance to regular treatment strategies is a big challenge in the treatment of castration-resistant prostate cancer. Combination of photothermal and photodynamic therapy (PTT/PDT) with chemotherapy offers unique advantages over monotherapy alone. However, free drugs, such as photosensitizers and chemotherapeutic agents, lack tumor-targeted accumulation and can be easily eliminated from the body. Moreover, most of the PTT drugs are hydrophobic and their organic solvents have in vivo toxicity, thereby limiting their potential in clinical translation. Herein, simple multifunctional nanoparticles (NPs) using IR780 (a near-infrared dye) and docetaxel (DTX)-loaded nanoplatform based on human serum albumin (HSA) (HSA@IR780@DTX) was developed for targeted imaging and for PTT/PDT with chemotherapy for the treatment of castration-resistant prostate cancer treatment. In this platform, HSA is a biocompatible nanocarrier that binds to both DTX and IR780. DTX and IR780, as hydrophobic drug, can induce the self-assembly of HSA proteins. Transmission electron microscopic imaging showed that NPs formed by self-assembly are spherical with a smooth surface with a hydrodynamic diameter of 146.5±10.8 nm. The cytotoxicity of HSA@IR780@DTX NPs with or without laser irradiation in prostate cancer cells (22RV1) was determined via CCK-8 assay. The antitumor effect of HSA@IR780@DTX plus laser irradiation was better than either HSA@IR780@DTX without laser exposure or single PTT heating induced by HSA@IR780 NPs under near-infrared laser, suggesting a significant combined effect in comparison to monotherapy. Near-infrared fluorescence imaging showed that HSA@IR780@DTX NPs could preferentially accumulate in tumors. In vivo therapeutic efficacy experiment showed that xenografted prostate tumors on mice treated with HSA@IR780@DTX plus near-infrared laser irradiation were completely inhibited, whereas tumors on mice treated with chemotherapy alone (HSA@DTX and HSA@IR780@DTX without laser) or PTT/PDT alone (HSA@IR780 with laser) showed moderate growth inhibition. Overall, HSA@IR780@DTX NPs showed notable targeting and theranostic potential for the treatment of castration-resistant prostate cancer.

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“…tumor | angiogenesis | VEGF | antiangiogenic therapy | adverse effects A ntiangiogenic therapy is a commonly used therapeutic approach for treatment of various human cancers (1)(2)(3)(4)(5)(6)(7)(8). Since the US Food and Drug Administration approval of the first anti-VEGF-based antiangiogenic drug, bevacizumab, for treatment of metastatic colorectal cancer (CRC) in human patients in 2004 (3), more than 10 years of clinical experiences with this agent and other antiangiogenic drugs have raised many clinically unfulfilled issues, including modest beneficial effects, lack of reliable biomarkers for patient selection, development of drug resistance, adverse effects, long-term therapy, and mechanistic rationale of combination therapy (1).…”

mentioning

confidence: 99%

Endocrine vasculatures are preferable targets of an antitumor ineffective low dose of anti-VEGF therapy

Zhang

Yang

Hosaka

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Anti-VEGF–based antiangiogenic drugs are designed to block tumor angiogenesis for treatment of cancer patients. However, anti-VEGF drugs produce off-tumor target effects on multiple tissues and organs and cause broad adverse effects. Here, we show that vasculatures in endocrine organs were more sensitive to anti-VEGF treatment than tumor vasculatures. In thyroid, adrenal glands, and pancreatic islets, systemic treatment with low doses of an anti-VEGF neutralizing antibody caused marked vascular regression, whereas tumor vessels remained unaffected. Additionally, a low dose of VEGF blockade significantly inhibited the formation of thyroid vascular fenestrae, leaving tumor vascular structures unchanged. Along with vascular structural changes, the low dose of VEGF blockade inhibited vascular perfusion and permeability in thyroid, but not in tumors. Prolonged treatment with the low-dose VEGF blockade caused hypertension and significantly decreased circulating levels of thyroid hormone free-T3 and -T4, leading to functional impairment of thyroid. These findings show that the fenestrated microvasculatures in endocrine organs are more sensitive than tumor vasculatures in response to systemic anti-VEGF drugs. Thus, our data support the notion that clinically nonbeneficial treatments with anti-VEGF drugs could potentially cause adverse effects.

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Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial

Cited by 260 publications

References 25 publications

Regulation of vascular endothelial growth factor in prostate cancer

Regulation of vascular endothelial growth factor in prostate cancer

Self-assembled albumin nanoparticles for combination therapy in prostate cancer

Endocrine vasculatures are preferable targets of an antitumor ineffective low dose of anti-VEGF therapy

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