A phase 2 cancer chemoprevention biomarker trial of isoflavone G-2535 (genistein) in presurgical bladder cancer patients

Edward Messing, Jason R. Gee, Daniel R. Saltzstein, Kyung Mann Kim, Anthony DiSant'Agnese, Jill Kolesar, Linda Harris, Adrienne Faerber, Thomas Havighurst, Jay M. Young, Mitchell Efros, Robert H. Getzenberg, Marcia A. Wheeler, Joseph Tangrea, Howard Parnes, Margaret House, J. Erik Busby, Raymond Hohl, Howard Bailey

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The soy compound genistein has been observed preclinically to inhibit bladder cancer growth with one potential mechanism being the inhibition of epidermal growth factor receptor phosphorylation (p-EGFR). A phase 2 randomized, placebo-controlled trial investigated whether daily, oral genistein (300 or 600 mg/d as the purified soy extract G-2535) for 14 to 21 days before surgery alters molecular pathways in bladder epithelial tissue in 59 subjects diagnosed with urothelial bladder cancer (median age, 71 years). G-2535 treatment was well tolerated; observed toxicities were primarily mild to moderate gastrointestinal or metabolic and usually not attributed to study drug. Genistein was detected in plasma and urine of subjects receiving G-2535 at concentrations greater than placebo subjects' but were not dose-dependent. Reduction in bladder cancer tissue p-EGFR staining between the placebo arm and the combined genistein arms was significant at the protocol-specified significance level of 0.10 (P = 0.07). This difference was most prominent when comparing the 300-mg group with placebo (P = 0.015), but there was no significant reduction in p-EGFR staining between the 600-mg group and placebo. No difference in normal bladder epithelium p-EGFR staining was observed between treatment groups. No significant differences in tumor tissue staining between treatment groups were observed for COX-2, Ki-67, activated caspase-3, Akt, p-Akt, mitogen-activated protein kinase (MAPK), or p-MAPK. No significant differences in urinary survivin or BLCA-4 levels between treatment groups were observed. Genistein displayed a possible bimodal effect (more effective at the lower dose) on bladder cancer tissue EGFR phosphorylation that should be evaluated further, possibly in combination with other agents.

Original languageEnglish (US)
Pages (from-to)621-630
Number of pages10
JournalCancer Prevention Research
Volume5
Issue number4
DOIs
StatePublished - Apr 1 2012

Fingerprint

Isoflavones
Genistein
Chemoprevention
Tumor Biomarkers
Urinary Bladder Neoplasms
Placebos
Staining and Labeling
Mitogen-Activated Protein Kinases
Urinary Bladder
Epithelium
Phosphorylation
Therapeutics
Ambulatory Surgical Procedures
Epidermal Growth Factor Receptor
Caspase 3
Randomized Controlled Trials
Urine
Growth
Pharmaceutical Preparations
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Messing, E., Gee, J. R., Saltzstein, D. R., Kim, K. M., DiSant'Agnese, A., Kolesar, J., ... Bailey, H. (2012). A phase 2 cancer chemoprevention biomarker trial of isoflavone G-2535 (genistein) in presurgical bladder cancer patients. Cancer Prevention Research, 5(4), 621-630. https://doi.org/10.1158/1940-6207.CAPR-11-0455
Messing, Edward ; Gee, Jason R. ; Saltzstein, Daniel R. ; Kim, Kyung Mann ; DiSant'Agnese, Anthony ; Kolesar, Jill ; Harris, Linda ; Faerber, Adrienne ; Havighurst, Thomas ; Young, Jay M. ; Efros, Mitchell ; Getzenberg, Robert H. ; Wheeler, Marcia A. ; Tangrea, Joseph ; Parnes, Howard ; House, Margaret ; Busby, J. Erik ; Hohl, Raymond ; Bailey, Howard. / A phase 2 cancer chemoprevention biomarker trial of isoflavone G-2535 (genistein) in presurgical bladder cancer patients. In: Cancer Prevention Research. 2012 ; Vol. 5, No. 4. pp. 621-630.
@article{33ba2bd32a74474d815b3f580e003f8c,
title = "A phase 2 cancer chemoprevention biomarker trial of isoflavone G-2535 (genistein) in presurgical bladder cancer patients",
abstract = "The soy compound genistein has been observed preclinically to inhibit bladder cancer growth with one potential mechanism being the inhibition of epidermal growth factor receptor phosphorylation (p-EGFR). A phase 2 randomized, placebo-controlled trial investigated whether daily, oral genistein (300 or 600 mg/d as the purified soy extract G-2535) for 14 to 21 days before surgery alters molecular pathways in bladder epithelial tissue in 59 subjects diagnosed with urothelial bladder cancer (median age, 71 years). G-2535 treatment was well tolerated; observed toxicities were primarily mild to moderate gastrointestinal or metabolic and usually not attributed to study drug. Genistein was detected in plasma and urine of subjects receiving G-2535 at concentrations greater than placebo subjects' but were not dose-dependent. Reduction in bladder cancer tissue p-EGFR staining between the placebo arm and the combined genistein arms was significant at the protocol-specified significance level of 0.10 (P = 0.07). This difference was most prominent when comparing the 300-mg group with placebo (P = 0.015), but there was no significant reduction in p-EGFR staining between the 600-mg group and placebo. No difference in normal bladder epithelium p-EGFR staining was observed between treatment groups. No significant differences in tumor tissue staining between treatment groups were observed for COX-2, Ki-67, activated caspase-3, Akt, p-Akt, mitogen-activated protein kinase (MAPK), or p-MAPK. No significant differences in urinary survivin or BLCA-4 levels between treatment groups were observed. Genistein displayed a possible bimodal effect (more effective at the lower dose) on bladder cancer tissue EGFR phosphorylation that should be evaluated further, possibly in combination with other agents.",
author = "Edward Messing and Gee, {Jason R.} and Saltzstein, {Daniel R.} and Kim, {Kyung Mann} and Anthony DiSant'Agnese and Jill Kolesar and Linda Harris and Adrienne Faerber and Thomas Havighurst and Young, {Jay M.} and Mitchell Efros and Getzenberg, {Robert H.} and Wheeler, {Marcia A.} and Joseph Tangrea and Howard Parnes and Margaret House and Busby, {J. Erik} and Raymond Hohl and Howard Bailey",
year = "2012",
month = "4",
day = "1",
doi = "10.1158/1940-6207.CAPR-11-0455",
language = "English (US)",
volume = "5",
pages = "621--630",
journal = "Cancer Prevention Research",
issn = "1940-6207",
publisher = "American Association for Cancer Research Inc.",
number = "4",

}

Messing, E, Gee, JR, Saltzstein, DR, Kim, KM, DiSant'Agnese, A, Kolesar, J, Harris, L, Faerber, A, Havighurst, T, Young, JM, Efros, M, Getzenberg, RH, Wheeler, MA, Tangrea, J, Parnes, H, House, M, Busby, JE, Hohl, R & Bailey, H 2012, 'A phase 2 cancer chemoprevention biomarker trial of isoflavone G-2535 (genistein) in presurgical bladder cancer patients', Cancer Prevention Research, vol. 5, no. 4, pp. 621-630. https://doi.org/10.1158/1940-6207.CAPR-11-0455

A phase 2 cancer chemoprevention biomarker trial of isoflavone G-2535 (genistein) in presurgical bladder cancer patients. / Messing, Edward; Gee, Jason R.; Saltzstein, Daniel R.; Kim, Kyung Mann; DiSant'Agnese, Anthony; Kolesar, Jill; Harris, Linda; Faerber, Adrienne; Havighurst, Thomas; Young, Jay M.; Efros, Mitchell; Getzenberg, Robert H.; Wheeler, Marcia A.; Tangrea, Joseph; Parnes, Howard; House, Margaret; Busby, J. Erik; Hohl, Raymond; Bailey, Howard.

In: Cancer Prevention Research, Vol. 5, No. 4, 01.04.2012, p. 621-630.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A phase 2 cancer chemoprevention biomarker trial of isoflavone G-2535 (genistein) in presurgical bladder cancer patients

AU - Messing, Edward

AU - Gee, Jason R.

AU - Saltzstein, Daniel R.

AU - Kim, Kyung Mann

AU - DiSant'Agnese, Anthony

AU - Kolesar, Jill

AU - Harris, Linda

AU - Faerber, Adrienne

AU - Havighurst, Thomas

AU - Young, Jay M.

AU - Efros, Mitchell

AU - Getzenberg, Robert H.

AU - Wheeler, Marcia A.

AU - Tangrea, Joseph

AU - Parnes, Howard

AU - House, Margaret

AU - Busby, J. Erik

AU - Hohl, Raymond

AU - Bailey, Howard

PY - 2012/4/1

Y1 - 2012/4/1

N2 - The soy compound genistein has been observed preclinically to inhibit bladder cancer growth with one potential mechanism being the inhibition of epidermal growth factor receptor phosphorylation (p-EGFR). A phase 2 randomized, placebo-controlled trial investigated whether daily, oral genistein (300 or 600 mg/d as the purified soy extract G-2535) for 14 to 21 days before surgery alters molecular pathways in bladder epithelial tissue in 59 subjects diagnosed with urothelial bladder cancer (median age, 71 years). G-2535 treatment was well tolerated; observed toxicities were primarily mild to moderate gastrointestinal or metabolic and usually not attributed to study drug. Genistein was detected in plasma and urine of subjects receiving G-2535 at concentrations greater than placebo subjects' but were not dose-dependent. Reduction in bladder cancer tissue p-EGFR staining between the placebo arm and the combined genistein arms was significant at the protocol-specified significance level of 0.10 (P = 0.07). This difference was most prominent when comparing the 300-mg group with placebo (P = 0.015), but there was no significant reduction in p-EGFR staining between the 600-mg group and placebo. No difference in normal bladder epithelium p-EGFR staining was observed between treatment groups. No significant differences in tumor tissue staining between treatment groups were observed for COX-2, Ki-67, activated caspase-3, Akt, p-Akt, mitogen-activated protein kinase (MAPK), or p-MAPK. No significant differences in urinary survivin or BLCA-4 levels between treatment groups were observed. Genistein displayed a possible bimodal effect (more effective at the lower dose) on bladder cancer tissue EGFR phosphorylation that should be evaluated further, possibly in combination with other agents.

AB - The soy compound genistein has been observed preclinically to inhibit bladder cancer growth with one potential mechanism being the inhibition of epidermal growth factor receptor phosphorylation (p-EGFR). A phase 2 randomized, placebo-controlled trial investigated whether daily, oral genistein (300 or 600 mg/d as the purified soy extract G-2535) for 14 to 21 days before surgery alters molecular pathways in bladder epithelial tissue in 59 subjects diagnosed with urothelial bladder cancer (median age, 71 years). G-2535 treatment was well tolerated; observed toxicities were primarily mild to moderate gastrointestinal or metabolic and usually not attributed to study drug. Genistein was detected in plasma and urine of subjects receiving G-2535 at concentrations greater than placebo subjects' but were not dose-dependent. Reduction in bladder cancer tissue p-EGFR staining between the placebo arm and the combined genistein arms was significant at the protocol-specified significance level of 0.10 (P = 0.07). This difference was most prominent when comparing the 300-mg group with placebo (P = 0.015), but there was no significant reduction in p-EGFR staining between the 600-mg group and placebo. No difference in normal bladder epithelium p-EGFR staining was observed between treatment groups. No significant differences in tumor tissue staining between treatment groups were observed for COX-2, Ki-67, activated caspase-3, Akt, p-Akt, mitogen-activated protein kinase (MAPK), or p-MAPK. No significant differences in urinary survivin or BLCA-4 levels between treatment groups were observed. Genistein displayed a possible bimodal effect (more effective at the lower dose) on bladder cancer tissue EGFR phosphorylation that should be evaluated further, possibly in combination with other agents.

UR - http://www.scopus.com/inward/record.url?scp=84864830787&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864830787&partnerID=8YFLogxK

U2 - 10.1158/1940-6207.CAPR-11-0455

DO - 10.1158/1940-6207.CAPR-11-0455

M3 - Article

VL - 5

SP - 621

EP - 630

JO - Cancer Prevention Research

JF - Cancer Prevention Research

SN - 1940-6207

IS - 4

ER -