Post-docetaxel in Castration-Resistant Prostate Cancer
Post-docetaxel in Castration-Resistant Prostate Cancer
Background: About 20% of patients with prostate cancer have an ECOG performance status (PS) ≥2 at diagnosis. We investigate if current treatment options for castration-resistant prostate cancer (CRPC) may decrease the risk of death even in patients with ECOG PS of 2.
Methods: PubMed was reviewed for phase III randomized trials in patients with CRPC progressed after docetaxel chemotherapy. Characteristics of each study and the relative hazard ratio (HR) for overall survival and 95% confidence interval (CI) were collected. Summary HR was calculated using random- or fixed-effects models depending on the heterogeneity of included studies.
Results: A total of 3,149 patients was available for meta-analysis. In the overall population, the experimental treatments decrease the risk of death by 31% (HR=0.69; 95% CI: 0.63–0.76; P<0.001). The activity of experimental treatments was similar in 2,859 patients with ECOG-PS=0 or 1 with a reduced risk of death of 31% (HR=0.69; 95% CI: 0.62–0.76). A total of 290 patients (9.2%) had ECOG-PS=2 and experimental treatments decreased the risk of death by 26% (HR=0.74; 95% CI: 0.56–0.98; P=0.035) compared with the controls even in this sub-group. When patients were stratified by type of treatment, the reduction of the risk of death was confirmed for hormonal therapies: abiraterone and enzalutamide (HR=0.72; 95% CI: 0.52–0.99; P=0.046), but not for chemotherapy (HR=0.81; 95% CI: 0.48–1.37; P=0.43).
Conclusions: We believe this is the first study reporting a benefit in second-line setting for CRPC patients previously treated with docetaxel and poor PS.
Prostate cancer is the most frequent cause of cancer in male; in 2012, about 241 740 new cases and 28 170 deaths have been estimated in the USA. Androgen-deprivation therapy with the luteinizing hormone-releasing analogue is the gold standard for advanced disease but despite the initial response, patients will develop progressive castration-resistant prostate cancer (CRPC).
Treatment of CRPC has completely changed in 2004 with the approval of docetaxel based on improvement of survival and control of disease compared with mitoxantrone (Mito). In recent years, several agents have reported to increase survival, delay disease progression and improve quality of life after docetaxel progression.
About 20% of patients with a new diagnosis of prostate cancer have an ECOG performance status (PS) ≥2, and the portion is probably higher in patients with advanced disease. Furthermore, PS and other factors such as baseline value of hemoglobin under the lower normal limit, weight loss and pain have been related to a short survival in patients with hormone sensitive and CRPC.
Despite these data, patients with poor PS enrolled in major clinical trials are less than 10%, and no evidence are currently available to the benefit of treating this subgroup. Therefore, we sought to investigate whether current available treatments for CRPC progressed after first-line docetaxel-based chemotherapy (CHT) may decrease the risk of death even in patients with poor PS.
Abstract and Introduction
Abstract
Background: About 20% of patients with prostate cancer have an ECOG performance status (PS) ≥2 at diagnosis. We investigate if current treatment options for castration-resistant prostate cancer (CRPC) may decrease the risk of death even in patients with ECOG PS of 2.
Methods: PubMed was reviewed for phase III randomized trials in patients with CRPC progressed after docetaxel chemotherapy. Characteristics of each study and the relative hazard ratio (HR) for overall survival and 95% confidence interval (CI) were collected. Summary HR was calculated using random- or fixed-effects models depending on the heterogeneity of included studies.
Results: A total of 3,149 patients was available for meta-analysis. In the overall population, the experimental treatments decrease the risk of death by 31% (HR=0.69; 95% CI: 0.63–0.76; P<0.001). The activity of experimental treatments was similar in 2,859 patients with ECOG-PS=0 or 1 with a reduced risk of death of 31% (HR=0.69; 95% CI: 0.62–0.76). A total of 290 patients (9.2%) had ECOG-PS=2 and experimental treatments decreased the risk of death by 26% (HR=0.74; 95% CI: 0.56–0.98; P=0.035) compared with the controls even in this sub-group. When patients were stratified by type of treatment, the reduction of the risk of death was confirmed for hormonal therapies: abiraterone and enzalutamide (HR=0.72; 95% CI: 0.52–0.99; P=0.046), but not for chemotherapy (HR=0.81; 95% CI: 0.48–1.37; P=0.43).
Conclusions: We believe this is the first study reporting a benefit in second-line setting for CRPC patients previously treated with docetaxel and poor PS.
Introduction
Prostate cancer is the most frequent cause of cancer in male; in 2012, about 241 740 new cases and 28 170 deaths have been estimated in the USA. Androgen-deprivation therapy with the luteinizing hormone-releasing analogue is the gold standard for advanced disease but despite the initial response, patients will develop progressive castration-resistant prostate cancer (CRPC).
Treatment of CRPC has completely changed in 2004 with the approval of docetaxel based on improvement of survival and control of disease compared with mitoxantrone (Mito). In recent years, several agents have reported to increase survival, delay disease progression and improve quality of life after docetaxel progression.
About 20% of patients with a new diagnosis of prostate cancer have an ECOG performance status (PS) ≥2, and the portion is probably higher in patients with advanced disease. Furthermore, PS and other factors such as baseline value of hemoglobin under the lower normal limit, weight loss and pain have been related to a short survival in patients with hormone sensitive and CRPC.
Despite these data, patients with poor PS enrolled in major clinical trials are less than 10%, and no evidence are currently available to the benefit of treating this subgroup. Therefore, we sought to investigate whether current available treatments for CRPC progressed after first-line docetaxel-based chemotherapy (CHT) may decrease the risk of death even in patients with poor PS.
