TY - JOUR
T1 - Initial biopsy Gleason score as a predictive marker for survival benefit in patients with castration-resistant prostate cancer treated with docetaxel
T2 - Data from the tax327 study
AU - Van Soest, Robert J.
AU - De Morrée, Ellen S.
AU - Shen, Liji
AU - Tannock, Ian F.
AU - Eisenberger, Mario A.
AU - De Wit, Ronald
N1 - Funding Information:
Financial disclosures: Robert J. van Soest certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: R. de Wit has received consultancy and speaker honoraria from Sanofi, Janssen, and Millenium; and research funding from Sanofi. L. Shen is employed by and owns stock in Sanofi. I. Tannock has received research funding from Sanofi. M. Eisenberger has received research funding from Sanofi. R.J. van Soest and E.S. de Morrée have no conflicts of interest to disclose.
PY - 2014/8
Y1 - 2014/8
N2 - Background Since 2004, docetaxel has been the standard first-line systemic therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). With abiraterone recently becoming available in the predocetaxel setting, it is warranted to identify subgroups of patients who may obtain the greatest benefit from docetaxel and particularly qualify for receiving docetaxel as first-line treatment for mCRPC. Objective We aimed to identify factors that could characterize subgroups of patients who obtain the greatest benefit from the use of docetaxel. Design, setting, and participants TAX327 was multinational, randomized, phase 3 study that was conducted from 2000 to 2002 in 1006 men with mCRPC. Intervention Patients were randomized to receive docetaxel every 3 wk (D3), weekly docetaxel (D1), or mitoxantrone every 3 wk (M3), each with prednisone. Outcome measurements and statistical analysis We investigated whether patients with poorly differentiated tumors (Gleason score ≥7) at diagnosis had greater benefit from D3 compared with M3 than patients with better differentiated tumors (Gleason score ≤6). Using a Cox model, we compared overall survival (OS) between the treatment groups within each subgroup of Gleason score. Results and limitations The TAX 327 data showed that the OS benefit of D3 versus M3 was greater in patients with high-grade tumors (median OS: 18.9 vs 14.5 mo; p = 0.009) than in patients with low-grade tumors (median OS: 21.6 vs 20.7 mo; p = 0.674). Limitations of a retrospective analysis apply. Conclusions The survival benefit obtained with docetaxel is most pronounced in patients with high-Gleason-score tumors (Gleason ≥7). In a time of shifting paradigms in mCRPC, with abiraterone becoming available prior to docetaxel chemotherapy, Gleason score may help in selecting patients who obtain the greatest benefit from docetaxel as first-line treatment for mCRPC. Prospective validation of these findings is warranted.
AB - Background Since 2004, docetaxel has been the standard first-line systemic therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). With abiraterone recently becoming available in the predocetaxel setting, it is warranted to identify subgroups of patients who may obtain the greatest benefit from docetaxel and particularly qualify for receiving docetaxel as first-line treatment for mCRPC. Objective We aimed to identify factors that could characterize subgroups of patients who obtain the greatest benefit from the use of docetaxel. Design, setting, and participants TAX327 was multinational, randomized, phase 3 study that was conducted from 2000 to 2002 in 1006 men with mCRPC. Intervention Patients were randomized to receive docetaxel every 3 wk (D3), weekly docetaxel (D1), or mitoxantrone every 3 wk (M3), each with prednisone. Outcome measurements and statistical analysis We investigated whether patients with poorly differentiated tumors (Gleason score ≥7) at diagnosis had greater benefit from D3 compared with M3 than patients with better differentiated tumors (Gleason score ≤6). Using a Cox model, we compared overall survival (OS) between the treatment groups within each subgroup of Gleason score. Results and limitations The TAX 327 data showed that the OS benefit of D3 versus M3 was greater in patients with high-grade tumors (median OS: 18.9 vs 14.5 mo; p = 0.009) than in patients with low-grade tumors (median OS: 21.6 vs 20.7 mo; p = 0.674). Limitations of a retrospective analysis apply. Conclusions The survival benefit obtained with docetaxel is most pronounced in patients with high-Gleason-score tumors (Gleason ≥7). In a time of shifting paradigms in mCRPC, with abiraterone becoming available prior to docetaxel chemotherapy, Gleason score may help in selecting patients who obtain the greatest benefit from docetaxel as first-line treatment for mCRPC. Prospective validation of these findings is warranted.
KW - Castration-resistant prostate cancer
KW - Gleason score
KW - Taxanes
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U2 - 10.1016/j.eururo.2013.08.007
DO - 10.1016/j.eururo.2013.08.007
M3 - Article
C2 - 23957945
AN - SCOPUS:84904059687
SN - 0302-2838
VL - 66
SP - 330
EP - 336
JO - European Urology
JF - European Urology
IS - 2
ER -