A Phase 2 Cancer Chemoprevention Biomarker Trial of Isoflavone G-2535 (Genistein) in Presurgical Bladder Cancer Patients

Messing, Edward M.; Gee, Jason; Saltzstein, Daniel R.; Kim, KyungMann; diSant’Agnese, P. Anthony; Kolesar, Jill; Harris, Linda S.; Faerber, Adrienne; Havighurst, Thomas C.; Young, Jay M.; Efros, Michael; Getzenberg, Robert H.; Wheeler, Marcia A.; Tangrea, Joseph A.; Parnes, Howard L.; House, Margaret G.; Busby, J. Erik; Hohl, Raymond J.; Bailey, Howard

doi:10.1158/1940-6207.capr-11-0455

Cited by 81 publications

(46 citation statements)

References 43 publications

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“…A significant reduction in bladder cancer tissue p-EGFR staining was observed in low dose treatment group as compared with placebo. However, there were no significant differences in tumor tissue staining between treatment groups for COX-2, Ki-67, activated caspase-3, Akt, p-Akt and MAPK (Messing et al, 2012).…”

Section: Natural Phytochemicals As Mtor Inhibitorsmentioning

confidence: 74%

“…Other clinical trials of genistein include Phase II study in patients who are undergoing surgery for bladder cancer, Phase II study in patients with prostate cancer as well as Phase I study of genistein in preventing breast or endometrial cancer in healthy postmenopausal women (Table 1). A Phase II randomized, placebo-controlled trial was carried out to investigate whether daily, oral genistein (300 or 600 mg/d) as purified soy extract for 14 to 21 days before surgery alters molecular pathways in bladder epithelial tissue in 59 subjects diagnosed with urothelial bladder cancer (Messing et al, 2012). Overall, genistein treatment was well tolerated and the observed toxicities were primarily mild to moderate.…”

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: 74%

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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“…Treatment was administered for 14-21 days before surgery. A detailed report about trial design, patient inclusion criteria, study agent G-2535 and trial conclusions can be found in the published Phase 2 Chemoprevention trial (4). …”

Section: Methodsmentioning

confidence: 99%

“…Genistein and daidzein pharmacokinetics were evaluated in plasma and urine samples by a validated reversed phase HPLC with UV detection with a lower limit of quantitation of 14.4 nMol for genistein, and 12.2 nMol for daidzein, converted from previously described limits of 3.9 ng/mL for genistein, and 3.1 ng/mL for daidzein (4,6). …”

Section: Methodsmentioning

confidence: 99%

Soy food frequency questionnaire does not correlate with baseline isoflavone levels in patients with bladder cancer

Kolesar

Pomplun

Havighurst

et al. 2014

J Oncol Pharm Pract

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Background The isoflavone genistein, a natural soy product with receptor tyrosine kinase inhibiting activity, as well as phytoestrogenic and other potential anticarcinogenic effects is being studied as an anticancer agent. Since isoflavones are commonly consumed in food products containing soy proteins, a method to control for baseline isoflavone consumption is needed. Methods HPLC was used to evaluate baseline plasma and urine concentrations of isoflavone in fifty-four participants with bladder cancer enrolled on a phase II chemoprevention study of G-2535. The soy food frequency questionnaire (Soy FFQ) was used to assess participant's baseline soy intake. The association between baseline isoflavone concentrations and intakes for genistein and daidzein was assessed by the Spearman's rank correlation coefficient. Results The majority of participants had no detectable genistein or daidzein in plasma at baseline. The median and range of values were 0 (0-1,480) nmol/L for genistein, and 0 (0-1,260) nmol/L for daidzein. In urine, the median and range of values were 91.0 (0-9,030) nmol/L for genistein and 623 (0-100,000) nmol/L for daidzein. The median and range of weekly estimated genistein intake was 0 (0-236) mg/wk; the median and range of weekly estimated daidzein intake was 0 (0-114) mg/wk. There was no relationship to soy intake as measured by the FFQ and baseline isoflavone levels in plasma or urine and the Spearman's rank correlation coefficients were not significant. Conclusion The Soy FFQ did not correlate with plasma or urine concentrations of either isoflavone. Impact Alternative methods for controlling for soy consumption, including measuring plasma and urine concentrations, in isoflavone chemoprevention trials should be considered.

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“…Our own experience in preoperative chemoprevention trials for prostate and bladder cancer has observed approximately 10% of screened participants were subsequently enrolled in the trial. 16 Several breast cancer window-of-opportunity trials have been conducted with novel chemopreventive agents. 10,[17][18][19] In these trials, the main factors that contribute to nonparticipation seem to be primarily related to protocol requirements or exclusions.…”

mentioning

confidence: 99%

Predictors of Willingness to Participate in Window-of-Opportunity Breast Trials

Wisinski

Faerber

Wagner

et al. 2013

Clinical Medicine & Research

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Objective: We conducted a pilot survey to evaluate breast cancer patients' willingness to participate in a preoperative chemoprevention (ie, window-of-opportunity) study. Design:A 27-question written survey was developed and administered to participants. Setting:A breast cancer specialty clinic at the University of Wisconsin Hospital and Clinics.Participants: 30 adult patients with newly diagnosed operable breast cancer participated after signing informed consent.Methods: A convenience sample of 30 participants was recruited from July 2005 through January 2006. Participants were administered the survey in clinic. Univariate ordinal logistic regression models were used to identify predictors of willingness to participate in window-of-opportunity trials.Results: Overall, 26.7% of respondents were willing to participate in a research trial between the time of breast cancer diagnosis and surgery. Univariate ordinal logistic regression models identified that women with a prior history of breast cancer (P=0.060), prior research participation (P=0.006), more education (P=0.034), and self-reported breast cancer knowledge (P=0.043) were more willing to participate. On average, women preferred to have surgery 7 days (range 1-14) after their diagnosis, but the actual average wait time between diagnostic biopsy and surgery was 37.5 days (standard deviation = 23.4 days). Conclusion:There is ample time before breast surgery to conduct preoperative window-ofopportunity trials. Interventions aimed at expanding patients' breast cancer knowledge may improve accrual to window-of-opportunity studies.

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A Phase 2 Cancer Chemoprevention Biomarker Trial of Isoflavone G-2535 (Genistein) in Presurgical Bladder Cancer Patients

Cited by 81 publications

References 43 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

Soy food frequency questionnaire does not correlate with baseline isoflavone levels in patients with bladder cancer

Predictors of Willingness to Participate in Window-of-Opportunity Breast Trials

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