Document Detail


Phase IB Randomized, Double-Blinded, Placebo-Controlled, Dose Escalation Study of Polyphenon E in Women with Hormone Receptor-Negative Breast Cancer.
MedLine Citation:
PMID:  22827973     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Epidemiologic data support an inverse association between green tea intake and breast cancer risk and numerous experimental studies have demonstrated the anti-tumor effects of its main component, epigallocatechin gallate (EGCG). We conducted a phase IB dose escalation trial in women with a history of stage I-III hormone receptor-negative breast cancer of an oral green tea extract, Polyphenon E (Poly E) 400mg, 600mg, 800mg bid or matching placebo for 6 months. The primary endpoint was to determine the maximum tolerated dose (MTD), defined as the dose that causes 25% dose limiting toxicity (DLT, grade≥2). Assignment to dose level was based upon an adaptive design, the continual reassessment method. A mammogram and random core biopsy of the contralateral breast were obtained at baseline and 6 months and serial blood/urine collections every 2 months for biomarker analyses. Forty women were randomized: 10 to placebo, 30 to Poly E (16 at 400mg, 11 at 600mg, 3 at 800mg). There was 1 DLT at 400mg (grade 3 rectal bleeding), 3 DLTs at 600mg (grade 2 weight gain, grade 3 indigestion and insomnia), and 1 DLT at 800mg (grade 3 liver function abnormality). The DLT rate at 600mg was 27% (3/11). Pharmacologic levels of total urinary tea polyphenols were achieved with all three dose levels of Poly E. Using a novel phase I trial design, we determined the MTD for Poly E to be 600mg bid. This study highlights the importance of assessing toxicity for any chemopreventive agent being developed for chronic use in healthy individuals.
Authors:
Katherine D Crew; Powel Brown; Heather Greenlee; Therese B Bevers; Banu K Arun; Clifford A Hudis; Heather L McArthur; Jenny Chang; Mothaffar F Rimawi; Lana Vornik; Terri L Cornelison; Antai Wang; Hanina H Hibshoosh; Aqeel Ahmed; Mary Beth Terry; Regina M Santella; Scott M Lippman; Dawn L Hershman
Related Documents :
9385483 - Comparative antihypertensive effectiveness of once-daily mibefradil and diltiazem cd. m...
11243303 - Comparison of candesartan versus enalapril in essential hypertension. italian candesart...
1122683 - Pharmacokinetics of procainamide intravenously and orally as conventional and slow-rele...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-24
Journal Detail:
Title:  Cancer prevention research (Philadelphia, Pa.)     Volume:  -     ISSN:  1940-6215     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101479409     Medline TA:  Cancer Prev Res (Phila)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Medicine and Epidemiology, Columbia University.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Simple method of paraphimosis reduction revisited: Point of technique and review of the literature.
Next Document:  Longitudinal Changes in Telomere Length and Chronic Stress Response: Implications for Cancer Prevent...