A phase 2 study of <scp>SRT</scp>501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma

Popat, Rakesh; Plesner, Torben; Davies, Faith E.; Cook, Gordon; Cook, Mark; Elliott, Peter J.; Jacobson, Eric; Gumbleton, Todd; Oakervee, Heather; Cavenagh, Jamie

doi:10.1111/bjh.12154

Cited by 183 publications

(126 citation statements)

References 8 publications

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“…The predominant study finding was an unexpected renal toxicity and low efficacy of SRT501 with nausea and vomiting which could have resulted in disease progression and dehydration. This study has demonstrated an unacceptable safety profile and minimal efficacy in patients with relapsed/refractory multiple myeloma (Popat et al, 2013). At least two more clinical trials on colorectal cancer were completed but no published data was noted on the outcome.…”

Section: Natural Phytochemicals As Mtor Inhibitorsmentioning

confidence: 96%

“…Unfortunately, a Phase II study of SRT501 (resveratrol) with bortezomib in patients w i t h r e l a p s e d a n d / o r refractory multiple myeloma has to be terminated recently (Popat et al, 2013). Out of 24 patients, 9 patients receiving SRT501 and bortezomib were withdrawn from the study, mainly due to serious adverse reactions.…”

Section: Natural Phytochemicals As Mtor Inhibitorsmentioning

confidence: 99%

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The mTOR Signalling Pathway in Cancer and the Potential mTOR Inhibitory Activities of Natural Phytochemicals

Tan¹,

Moad²,

Tan³

2014

Asian Pacific Journal of Cancer Prevention

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The mammalian target of rapamycin (mTOR) kinase plays an important role in regulating cell growth and cell cycle progression in response to cellular signals. It is a key regulator of cell proliferation and many upstream activators and downstream effectors of mTOR are known to be deregulated in various types of cancers. Since the mTOR signalling pathway is commonly activated in human cancers, many researchers are actively developing inhibitors that target key components in the pathway and some of these drugs are already on the market. Numerous preclinical investigations have also suggested that some herbs and natural phytochemicals, such as curcumin, resveratrol, timosaponin III, gallic acid, diosgenin, pomegranate, epigallocatechin gallate (EGCC), genistein and 3,3'-diindolylmethane inhibit the mTOR pathway either directly or indirectly. Some of these natural compounds are also in the clinical trial stage. In this review, the potential anti-cancer and chemopreventive activities and the current status of clinical trials of these phytochemicals are discussed.

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Section: Natural Phytochemicals As Mtor Inhibitorsmentioning

confidence: 96%

Section: Natural Phytochemicals As Mtor Inhibitorsmentioning

confidence: 99%

The mTOR Signalling Pathway in Cancer and the Potential mTOR Inhibitory Activities of Natural Phytochemicals

Tan¹,

Moad²,

Tan³

2014

Asian Pacific Journal of Cancer Prevention

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“…It is important to note that there is some evidence that resveratrol may have adverse effects in certain cancer patients. In a phase II clinical trial involving relapsed or refractory multiple myeloma patients, resveratrol at a dose of 5 g per day caused adverse events (including nausea, diarrhea, fatigue, and renal toxicity), which may have contributed to the death of one patient and caused the investigators to prematurely end the study (Popat et al 2013). The authors note that this high dose has been shown to be safe in other clinical trials in healthy patients.…”

Section: Clinical Studiesmentioning

confidence: 99%

Resveratrol and cancer: focus on in vivo evidence

Carter¹,

D’Orazio²,

Pearson³

2014

Endocrine-Related Cancer

448

281

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Resveratrol is a naturally occurring polyphenol that provides a number of anti-aging health benefits including improved metabolism, cardioprotection, and cancer prevention. Much of the work on resveratrol and cancer comes from in vitro studies looking at resveratrol actions on cancer cells and pathways. There are, however, comparatively fewer studies that have investigated resveratrol treatment and cancer outcomes in vivo, perhaps limited by its poor bioavailability when taken orally. Although research in cell culture has shown promising and positive effects of resveratrol, evidence from rodents and humans is inconsistent. This review highlights the in vivo effects of resveratrol treatment on breast, colorectal, liver, pancreatic, and prostate cancers. Resveratrol supplementation in animal models of cancer has shown positive, neutral as well as negative outcomes depending on resveratrol route of administration, dose, tumor model, species, and other factors. Within a specific cancer type, there is variability between studies with respect to strain, age, and sex of animal used, timing and method of resveratrol supplementation, and dose of resveratrol used to study cancer endpoints. Together, the data suggest that many factors need to be considered before resveratrol can be used for human cancer prevention or therapy.

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“…Subsequent clinical trials are currently investigating this dose limit [307,310]. Resveratrol's poor bioavailability is a significant issue with regard to extrapolating its effects to humans, and various approaches have been created to enhance its bioavailability [311], including consuming it with various foods [312], using it in combination with an additional phytochemical piperine [313], and using a prodrug approach [314], micronized powders [315,316], or nanotechnological formulations [317][318][319].…”

Section: Clinical Trials With Resveratrolmentioning

confidence: 99%

Chemically-Induced DNA Damage, Mutagenesis, and Cancer

2018

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A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma

Abstract: Additional Supporting Information may be found in the online version of this article:Fig S1. CD4 + T cells are highly effective inducers of CLL cell proliferation. Fig S2. Analysis of proliferative potential of CLL cells in in vitro cultures with respect to common risk factors.

Cited by 183 publications

References 8 publications

The mTOR Signalling Pathway in Cancer and the Potential mTOR Inhibitory Activities of Natural Phytochemicals

The mTOR Signalling Pathway in Cancer and the Potential mTOR Inhibitory Activities of Natural Phytochemicals

Resveratrol and cancer: focus on in vivo evidence

Chemically-Induced DNA Damage, Mutagenesis, and Cancer

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