Efficacy of carboplatin-taxane combinations in the management of castration-resistant prostate cancer: a pooled analysis of seven prospective clinical trials.
BACKGROUND
Docetaxel is associated with prolonged survival in castration-resistant prostate cancer (CRPC). Platinum compounds have modest but distinct single-agent activity. Carboplatin may have greatest potential for benefit when combined with taxanes. We investigated whether there is a subset of patients with CRPC for whom the efficacy of combination taxane-estramustine-carboplatin (TEC) chemotherapy may be greatest.


METHODS
Individual patient data (n = 310) were obtained from seven trials using TEC chemotherapy. Prostate-specific antigen (PSA) response was defined as > or = 50% post-therapy decline from baseline. Overall survival was defined from baseline to death from any cause. Logistic and Cox regression were used to investigate heterogeneity in outcome to TEC by patient and disease characteristics. Predicted survival probabilities were calculated from the Halabi Cancer and Leukemia Group B (CALGB) nomogram.


RESULTS
The pooled PSA response proportion was 69% [95% confidence interval (CI) 56% to 80%]. There was no evidence of differential PSA response by disease characteristics. Established prognostic factors were associated with survival. The pooled 12-month survival estimate of 79% (95% CI 71% to 84%) was higher than the median 59% 12-month nomogram-predicted survival.


CONCLUSIONS
TEC chemotherapy has significant clinical activity in CRPC. A randomized, controlled trial evaluating the addition of carboplatin to taxane-based chemotherapy is needed to elucidate the value of carboplatin in CRPC.
Regan
M M
MM
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA. Electronic address: mregan@jimmy.harvard.edu.
O'Donnell
E K
EK
Beth Israel Deaconess Medical Center, Boston, MA.
Kelly
W K
WK
Department of Medicine and Surgery, Yale University, New Haven, CT.
Halabi
S
S
Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC.
Berry
W
W
US Oncology, Inc., Houston, TX; Cancer Centers of North Carolina, Cary, NC, USA.
Urakami
S
S
Department of Urology, Shimane University School of Medicine, Izumo, Japan.
Kikuno
N
N
Department of Urology, Shimane University School of Medicine, Izumo, Japan.
Oh
W K
WK
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage*; D002369:Castration; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D043823:Taxoids / Q000008:administration & dosage*; D017211:Treatment Failure; D016896:Treatment Outcome
D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane; D016190:Carboplatin