|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 26, No 18 (June 20), 2008: pp. 2959-2965 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.15.1928 Phase II Trial of Docetaxel With Rapid Androgen Cycling for Progressive Noncastrate Prostate Cancer
From the Genitourinary Oncology Service, Department of Medicine, Department of Epidemiology and Biostatistics, and the Department of Clinical Chemistry, Memorial Sloan-Kettering Cancer Center; Department of Medicine, Joan and Sanford Weill College of Medicine, New York, NY; Prostate Cancer Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; and Pharmaceutical Sciences Department, St Jude Children's Research Hospital, Memphis, TN Corresponding author: Howard I. Scher, MD, Sidney Kimmel Center for Prostate and Urologic Cancers, Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, New York 10021; e-mail: scherh{at}mskcc.org Purpose We evaluated rapid androgen cycling in combination with docetaxel for men with progressive noncastrate prostate cancers.
Patients and Methods Noncastrate patients with Results A higher proportion of patients achieved the undetectable PSA outcome at 18 months in cohort 2 relative to cohort 1 (13% v 0%). The 16% incidence of febrile neutropenia was higher than that observed in patients was castration-resistant disease, which may have been related to a 50% reduction in overall docetaxel clearance in the noncastrate group. There was no alteration in CYP3A4 activity (P = .87) or docetaxel clearance (P = .88) between cycles. Conclusion The undetectable PSA end point allows for a rapid screening of interventions for further study. Increasing the number of docetaxel cycles after a shorter period of testosterone repletion, and a longer duration of testosterone depletion, increased the proportion of men who achieved an undetectable PSA. The higher-than-expected incidence of febrile neutropenia may have been related to the reduced overall docetaxel clearance in patients with noncastrate versus castrate testosterone levels. Supported by the Prostate Cancer Foundation, grant No. P50-CA92629 Specialized Program of Research Excellence from the National Cancer Institute, Sanofi-aventis Grant-in-Aid No. 16143 for investigator-sponsored trial 16143, and by the Department of Defense Prostate Cancer Research Program Clinical Consortium Grant No. PC051382 (Johns Hopkins W81XWH-06-1-0241 to D.R.). Presented in part in abstract format at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 1-5, 2007; and at the American Society of Clinical Oncology Prostate Cancer Symposium, Orlando, FL, February 22-24, 2007. Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Related Editorial
This article has been cited by other articles:
|
||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
6 months of hormone therapy were eligible. Cohort 1 (62 patients) received six 28-day cycles of docetaxel (75 mg/m2), leuprolide, and 7 days of topical testosterone. Cohort 2 (38 patients) received nine 21-day cycles of docetaxel (70 mg/m2), leuprolide, and 3 days of testosterone. The primary end point was the proportion of patients at 18 months who achieved noncastrate testosterone levels (> 150 ng/dL) and an undetectable prostate-specific antigen (PSA; 
