Phase II trial of docetaxel with rapid androgen cycling for progressive noncastrate prostate cancer Journal Article


Authors: Rathkopf, D.; Carducci, M. A.; Morris, M. J.; Slovin, S. F.; Eisenberger, M. A.; Pili, R.; Denmeade, S. R.; Kelsen, M.; Curley, T.; Halter, M.; Collins, C.; Fleisher, M.; Heller, G.; Baker, S. D.; Scher, H. I.
Article Title: Phase II trial of docetaxel with rapid androgen cycling for progressive noncastrate prostate cancer
Abstract: Purpose: We evaluated rapid androgen cycling in combination with docetaxel for men with progressive noncastrate prostate cancers. Patients and Methods: Noncastrate patients with ≤ 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; ≤ 0.05, ≤ 0.5, or ≤ 2.0 ng/mL with prior prostatectomy, radiation therapy, or no definitive therapy, respectively). Cytochrome P450 3A4 (CYP3A4) activity and docetaxel pharmacokinetics were evaluated. 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. © 2008 by American Society of Clinical Oncology.
Keywords: adult; controlled study; treatment outcome; aged; aged, 80 and over; middle aged; major clinical study; androgen; clinical trial; fatigue; neutropenia; area under the curve; cancer combination chemotherapy; cancer growth; multimodality cancer therapy; treatment duration; unspecified side effect; cancer radiotherapy; antineoplastic agent; prostate specific antigen; metabolism; controlled clinical trial; multiple cycle treatment; phase 2 clinical trial; steady state; antineoplastic combined chemotherapy protocols; peripheral neuropathy; cohort analysis; dexamethasone; enzyme activity; docetaxel; cancer hormone therapy; febrile neutropenia; hyperglycemia; prostate cancer; prostate-specific antigen; prostatic neoplasms; leuprorelin; blood; prostatectomy; dosage schedule comparison; multicenter study; prostate tumor; drug clearance; taxoids; hot flush; maximum plasma concentration; drug blood level; castration; testosterone blood level; drug half life; recombinant granulocyte colony stimulating factor; testosterone; leuprolide; cytochrome p450; taxoid; cytochrome p450 3a4; cyp3a protein, human; cytochrome p-450 enzyme system
Journal Title: Journal of Clinical Oncology
Volume: 26
Issue: 18
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2008-06-20
Start Page: 2959
End Page: 2965
Language: English
DOI: 10.1200/jco.2007.15.1928
PUBMED: 18565882
PROVIDER: scopus
PMCID: PMC3051836
DOI/URL:
Notes: --- - "Cited By (since 1996): 8" - "Export Date: 17 November 2011" - "CODEN: JCOND" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Glenn Heller
    295 Heller
  2. Susan Slovin
    184 Slovin
  3. Michael Morris
    274 Morris
  4. Dana Elizabeth Rathkopf
    142 Rathkopf
  5. Moshe Kelsen
    3 Kelsen
  6. Martin Fleisher
    237 Fleisher
  7. Howard Scher
    817 Scher