Journal article
A Phase 2 Cancer Chemoprevention Biomarker Trial of Isoflavone G-2535 (Genistein) in Presurgical Bladder Cancer Patients
Cancer prevention research (Philadelphia, Pa.), Vol.5(4), pp.621-630
04/01/2012
DOI: 10.1158/1940-6207.CAPR-11-0455
PMCID: PMC3324663
PMID: 22293631
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. Cancer Prev Res; 5(4); 621-30. (C) 2012 AACR.
Details
- Title: Subtitle
- A Phase 2 Cancer Chemoprevention Biomarker Trial of Isoflavone G-2535 (Genistein) in Presurgical Bladder Cancer Patients
- Creators
- Edward Messing - Johns Hopkins UniversityJason R. Gee - University of Wisconsin Carbone Cancer CenterDaniel R. Saltzstein - Urology San AntonioKyungMann Kim - University of Wisconsin Carbone Cancer CenterAnthony diSant'Agnese - Johns Hopkins UniversityJill Kolesar - University of IowaLinda Harris - Johns Hopkins UniversityAdrienne Faerber - Johns Hopkins UniversityThomas Havighurst - Johns Hopkins UniversityJay M. Young - Johns Hopkins UniversityMitchell Efros - Johns Hopkins UniversityRobert H. Getzenberg - Johns Hopkins UniversityMarcia A. Wheeler - Yale UniversityJoseph Tangrea - Johns Hopkins UniversityHoward Parnes - National Cancer InstituteMargaret House - National Cancer InstituteJ. Erik Busby - Johns Hopkins UniversityRaymond Hohl - University of IowaHoward Bailey - University of Wisconsin Carbone Cancer Center
- Resource Type
- Journal article
- Publication Details
- Cancer prevention research (Philadelphia, Pa.), Vol.5(4), pp.621-630
- DOI
- 10.1158/1940-6207.CAPR-11-0455
- PMID
- 22293631
- PMCID
- PMC3324663
- NLM abbreviation
- Cancer Prev Res (Phila)
- ISSN
- 1940-6207
- eISSN
- 1940-6215
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 10
- Grant note
- N01 CN35153; P30 CA014520; 1UL1RR025011 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 04/01/2012
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984695800902771
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