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Metastatic castrate-resistant prostate cancer (mCRPC) is the last stage of prostate cancer. Although new hormonal agents and taxane-based chemotherapies occurred for mCRPC treatment, the overall survival of mCRPC patients is limited. Olaparib is an inhibitor of poly ADP-ribose polymerase (PARP), which has a key role in DNA damage response. It has been approved for ovarian cancer and breast cancer treatment. PROfound, a phase III clinical trial of olaparib in mCRPC treatment, has been reported in 2019 ESMO and 2020 ASCO-GU. In this paper, we will bring the results and updates of PROfound.
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Background and purpose: Docetaxel plus prednisone chemotherapy can improve the patients' survival for castrate-resistant prostate cancer. Angiogenesis inhibitors can also inhibit the growth of tumor. The curative effect of combined treatment is still not clear. This study aimed to evaluate the efficacy of docetaxel plus prednisone combined with thalidomide in treating castrate-resistant prostate cancer (CRPC) patients with bone metastasis. Methods:A total number of 78 CRPC patients were selected in Fuzhou General Hospital from Dec. 2008 to Jun. 2015. Seventy-eight patients were divided into two groups: 40 patients in chemotherapy group (docetaxel plus prednisone) and 38 patients in combined treatment group (docetaxel plus prednisone combined with thalidomide). A total number of 78 subjects were evaluated by the effective rate, the remission rate of bone pain, the prostate specific antigen (PSA) progression-free surviv-al, the overall survival and adverse effect. Results: The response rate (65.79%) and the remission rate of bone pain (86.84%) in combined treatment group were both higher than those in chemotherapy group (40.00% and 60.00%, P0.05). The rates of adverse effects including peripheral neuritis and lethargy in combined treatment group (26.32% and 55.26%) were higher than those in chemotherapy group (5.00% and 17.50%, P<0.05). Conclusion: Thalidomide combined with docetaxel plus prednisone in CRPC patients with bone metastasis can prolong the PSA progression-free survival and overall survival. The adverse effects are mild. It may become a new choice of treatment for CRPC.
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Polo-like kinase 1 (PLK1) is a highly conserved serine/threonine protein kinase that has attracted research attention be-cause it plays a critical role in mitosis regulation. PLK1 is overexpressed in 80%of human tumors, which indicates a poor prognosis in most tumors. PLK1 is one of the most promising targets for antitumor therapy because it is upregulated in castrate-resistant prostate can-cer (CRPC). This review focused on the basic structure and function of PLK1, the relationship between PLK1 and CRPC occurrence and progression, and CRPC treatment by inhibiting PLK1. This study provides a theoretical basis for the targeted molecular therapy of CRPC.
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Objective To explore the prognostic value of modified Glasgow prognostic score (mGPS) and risk factors in predicting overall survival (OS) in the castrate-resistant prostate cancer (CRPC) treated with docetaxel-based chemotherapy.Methods We retrospectively analyzed the data of 48 consecutive Chinese patients with CRPC received docetaxel-based chemotherapy in our institution from January 2008 to January 2012.Patients were divided into three groups according to the mGPS:0,1 and 2 score groups,and compare the OS among the three groups.Variables that were influenced the efficacy of chemotherapy were included in the univariate analysis and multivariate model.Survival analysis was performed using Kaplan-Meier curves,and the differences in overall survival rates were assessed using the Logrank test.Results The follow-up was performed until April 2014.There were 48 CRPC patients including mGPS 0 score group 30 cases,mGPS 1 score group 11 cases and mGPS 2 score 7 cases.The median OS was 22,11,9 months,respectively,P＜0.01.Univariate analysis showed that:prechemotherapy baseline total prostate-specific antigen (tPSA),Eastern Cooperative Oncology Group (ECOG) score,the number of chemotherapy cycle,visceral metastasis and PSA response were associated with poor prognosis (P＜0.05).Multivariate analysis showed that:prechemotherapy mGPS 1-2 score,baseline tPSA＞60 μg/L,the number of cycles of chemotherapy≤5,with visceral metastasis and PSA response in patients with CRPC were independent risk factors for prognosis in the CRPC treated with docetaxel-based chemotherapy.Conclusion mGPS is an independent risk factor for prognosis in the CRPC patients treated with docetaxel-based chemotherapy.
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Objective To investigate the risk factors for castrate-resistant prostate cancer (CRPC) after prostate cancer treated with androgen deprivation therapy (ADT) within 1 year.Methods One hundred and thirty-one prostate cancer patients treated with ADT in our institute between Jan.2008 and Jan.2011 were selected for this study.Patients were followed up by telephone or in clinic,including serum testosterone,serum PSA,clinical symptoms,imaging studies,digital rectal examination (DRE),survival data,PSA nadir,time to PSA nadir and et al.We mainly studied the CRPC after prostate cancer treated with ADT within 1 year.In the 131 patients,the median age was 70 (ranged from 44-89) years.There were 13 patients (9.9％) less than 60 years,43 patients (32.8％) between 60 and 69 years,62 patients (47.3％) between 70 and 79 years,13 patients (9.9％) more than 80 years.The average body mass index (BMI) was 23.0 (ranged from 14.4-34.4) kg/m2.There were 10 patients less than 18.5 kg/m2,77 patients between 18.5 and 24.0 kg/m2,34 patients between 24.1 and 28.0 kg/m2,and 10 patients more than 28.0 kg/m2.The initial PSA was between 0.3 and 4 707.0 μg/L,there were 19 patients (14.5％) less than 20 μg/L,45 patients (34.4％) between 20 and 99 μg/L,67 patients (51.1％) more than 100 μg/L.One patient (0.7％) was in T1,39 patients (29.8％) in T2,59 patients (45.0％) in T3,32 patients (24.4％) in T4.5 patients (3.8％) were with Gleason score 4,13 patients (9.9％) were with Gleason score 5,24 patients (18.3％) were with Gleason score 6,51 patients (38.9％) were with Gleason score 7,26 patients (19.8％) were with Gleason score 8,9 patients (6.9％) were with Gleason score 9,3 patients (2.3％) were with Gleason score 10.Results There were 32 of 131 patients (24.4％) progressed to CRPC after treated with ADT within 1 year.In the CRPC group,there were 3 patients less than 60 years,15 patients between 60 and 69 years,12 patients between 70 and 79 years,2 patients more than 79 years; 3 patients were less than 18.5 kg/m2,19 patients were between 18.5 and 24.0 kg/m2,7 patients were between 24.0 and 28.0 kg/m2,3 patients were more than 28.0 kg/m2 ; 4 patients were less than 20 μg/L,6 patients were between 20 and 100 μg/L,22 patients were more than 100 μg/L; 4 patients were in T2,13 patients were in T3,15 patients were in T4; 2 patients were with Gleason score 6,11 patients were with Gleason score 7,11 patients were with Gleason score 8,6 patients were with Gleason score 9,2 patients were with Gleason score 10; 29 patients were with metastasis,3 patients without metastasis.Clinical stage (P =0.001),Gleason score (P＜0.001) and metastasis (P=0.011) were statistically significant between the CRPC within 1 year group and the rest group.Conclusions The clinical stage and Gleason score are the risk factors of CRPC treated with ADT within 1 year.The higher of the clinical stage and Gleason score,the greater risk to be the CRPC within 1 year.