TY - JOUR
T1 - Phase 2 Study of Weekly Paclitaxel Plus Estramustine in Metastatic Hormone-Refractory Prostate Carcinoma
T2 - ECOG-ACRIN Cancer Research Group (E1898) Trial
AU - Wong, Yu Ning
AU - Manola, Judith
AU - Hudes, Gary R.
AU - Roth, Bruce J.
AU - Moul, Judd W.
AU - Barsevick, Andrea M.
AU - Scher, Richard M.
AU - Volk, Michael J.
AU - Vaughn, David J.
AU - Williams, Stephen D.
AU - Fisch, Michael J.
AU - Cella, David
AU - Carducci, Michael A.
AU - Wilding, George
N1 - Funding Information:
This study was coordinated by the ECOG-ACRIN Cancer Research Group (Peter J. O'Dwyer, MD, and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute/National Institutes of Health under the following awards: CA180820, CA180794, CA189828, CA180795, CA180799, CA180802, CA180847, CA180858, CA189956, and CA180857. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/4
Y1 - 2018/4
N2 - To assess the combination of estramustine and weekly paclitaxel with metastatic castration-resistant prostate cancer, 74 eligible patients were treated. The response rate was not better than those noted in subsequent phase 3 studies of docetaxel-based therapies. Because better-tolerated therapies have since been approved, we cannot recommend further development of this regimen. Introduction: This multicenter phase 2 study assessed the combination of estramustine and weekly paclitaxel with metastatic castration-resistant prostate cancer (CRPC). Patients and Methods: We enrolled 77 patients who had received no prior chemotherapy for CRPC between 1998 and 2000; a total of 74 subjects were eligible for the study. Each 8-week cycle included paclitaxel 90 mg/m2 provided intravenously weekly for 6 weeks, followed by 2 weeks off therapy and oral estramustine 280 mg twice daily for 3 days beginning 24 hours before the first dose of paclitaxel. The primary end point was rate of objective or prostate-specific antigen (PSA) response at 16 weeks. A 50% response rate was considered of further interest. Results: Eligible patients received a median of 3 cycles (range, 1-10 cycles). The response rate among patients with measurable disease was 34% (95% confidence interval [CI], 19-52). The PSA response rate was 58% (95% CI, 47-70). Clinical benefit rate was 45% (95% CI, 33-57). The median progression-free survival was 5.9 months (95% CI, 4.4-6.7). The median overall survival was 17.6 months (95% CI, 14.6-20.8). The most common clinical grade 3/4 toxicities were fatigue (14%) and sensory neuropathy (7%). Grade 3/4 hematologic toxicities included lymphopenia (21%) and anemia (9%). There was one toxicity-related death. Quality-of-life scores improved by week 8, but the change was not statistically significant. Conclusion: The combination has activity defined by PSA declines in CRPC but did not meet the protocol-specified end point for efficacy as defined by objective response rate. Since this study was conducted, more effective, better-tolerated regimens have been developed.
AB - To assess the combination of estramustine and weekly paclitaxel with metastatic castration-resistant prostate cancer, 74 eligible patients were treated. The response rate was not better than those noted in subsequent phase 3 studies of docetaxel-based therapies. Because better-tolerated therapies have since been approved, we cannot recommend further development of this regimen. Introduction: This multicenter phase 2 study assessed the combination of estramustine and weekly paclitaxel with metastatic castration-resistant prostate cancer (CRPC). Patients and Methods: We enrolled 77 patients who had received no prior chemotherapy for CRPC between 1998 and 2000; a total of 74 subjects were eligible for the study. Each 8-week cycle included paclitaxel 90 mg/m2 provided intravenously weekly for 6 weeks, followed by 2 weeks off therapy and oral estramustine 280 mg twice daily for 3 days beginning 24 hours before the first dose of paclitaxel. The primary end point was rate of objective or prostate-specific antigen (PSA) response at 16 weeks. A 50% response rate was considered of further interest. Results: Eligible patients received a median of 3 cycles (range, 1-10 cycles). The response rate among patients with measurable disease was 34% (95% confidence interval [CI], 19-52). The PSA response rate was 58% (95% CI, 47-70). Clinical benefit rate was 45% (95% CI, 33-57). The median progression-free survival was 5.9 months (95% CI, 4.4-6.7). The median overall survival was 17.6 months (95% CI, 14.6-20.8). The most common clinical grade 3/4 toxicities were fatigue (14%) and sensory neuropathy (7%). Grade 3/4 hematologic toxicities included lymphopenia (21%) and anemia (9%). There was one toxicity-related death. Quality-of-life scores improved by week 8, but the change was not statistically significant. Conclusion: The combination has activity defined by PSA declines in CRPC but did not meet the protocol-specified end point for efficacy as defined by objective response rate. Since this study was conducted, more effective, better-tolerated regimens have been developed.
KW - Castration resistant
KW - Chemotherapy
KW - Clinical trials
KW - Metastases
KW - Prostate cancer
UR - https://www.scopus.com/pages/publications/85035039905
U2 - 10.1016/j.clgc.2017.10.001
DO - 10.1016/j.clgc.2017.10.001
M3 - Article
C2 - 29173976
AN - SCOPUS:85035039905
SN - 1558-7673
VL - 16
SP - e315-e322
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 2
ER -