• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3969-3972
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• 2015

Background: This analysis was conducted to evaluate the efficacy and safety of lenalidomide based regimen in treating patients with castration-resistant prostate cancer. Materials and Methods: Clinical studies evaluating the efficacy and safety of lenalidomide based regimens on response and safety for patients with castration-resistant prostate cancer were identified using a predefined search strategy. A pooled response rate (rate of PSA level decline of ${\geq}50%$) to treatment was calculated. Results: In lenalidomide based regimen, 3 clinical studies which including 98 patients with castration-resistant prostate cancer were considered eligible for inclusion. These lenalidomide based regimens included cisplatin, doxorubicin, or GM-CSF. Pooled analysis suggested that, in all patients, the pooled PSA level decline of ${\geq}50%$ was 13.3% (13/98) in lenalidomide based regimens. Fatigue, nausea and vomitting were the main side effects. No grade III or IV renal or liver toxicity were observed. No treatment related death occurred in patients with lenalidomide based regimens. Conclusions: This evidence based analysis suggests that lenalidomide based regimens are associated with mild response rate and acceptable toxicities for treating patients with castration-resistant prostate cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6167-6169
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• 2015

Prostate cancer is common all around the world. Hormonal therapy is the mainstay of therapy, however castration-resistant prostate cancer (CRPC) becomes a serious problem and needs further clinical trials with novel agents. Novel agents like cabazitaxel, abireterone acetate or enzalutamide are encouraging but we do not know which one is the best in metastatic CRPC. In here, treatment modalities for metastatic CRPC are discussed witha mini-review of the literature.

• The Korean Journal of Urological Oncology
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• v.16 no.3
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• pp.97-102
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• 2018

Prostate cancer is usually managed by androgen deprivation therapy after failure of primary treatment. However, such therapies are only temporarily effective in prostate cancer patients, and the most patients experience the progression to castration-resistant prostate cancer (CRPC). Docetaxel chemotherapy is conventional effective treatment for CRPC but has many adverse effects. In CRPC patients, treatment decisions were not typically base on the recognitions of inter-individual differences. Therefore, there are growing interests for precision medicine in CRPC. In this review, we summarized the precision medicine such as candidate target genes and potential therapies in CRPC.

• Genomics & Informatics
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• v.16 no.3
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• pp.71-74
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• 2018

Because castration-resistant prostate cancer (CRPC) does not respond to androgen deprivation therapy and has a very poor prognosis, it is critical to identify a prognostic indicator for predicting high-risk patients who will develop CRPC. Here, we report a dataset of whole genomes from four pairs of primary prostate cancer (PC) and CRPC samples. The analysis of the paired PC and CRPC samples in the whole-genome data showed that the average number of somatic mutations per patients was 7,927 in CRPC tissues compared with primary PC tissues (range, 1,691 to 21,705). Our whole-genome sequencing data of primary PC and CRPC may be useful for understanding the genomic changes and molecular mechanisms that occur during the progression from PC to CRPC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1313-1320
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• 2014

Introduction: Although most prostate cancers initially respond to castration with luteinizing hormonereleasing analogues or bilateral orchiectomy, progression eventually occurs. Based on the exciting results of several randomized controlled trials (RCTs), it seems that patients with metastatic castration-resistant prostate cancer (mCRPC) might benefit more from treatment withabiraterone. Therefore we conducted a systematic review to evaluate the efficacy and toxicity of abiraterone in the treatment of mCRPC. Methods: Literature was searched from Embase, PubMed, Web of Science, and Cochrane Library up to July, 2013. Quality of the study was evaluated according to the Cochrane's risk of bias of randomized controlled trial (RCT) tool, then the Grading of Recommendations Assessment, Development and Evaluation (GRADE) System was used to rate the level of evidence. Stata 12.0 was used for statistical analysis. Summary data from RCTs comparing abiraterone plus prednisone versus placebo plus prednisone for mCRPC were meta-analyzed. Pooled hazard ratios (HRs) for overall survival (OS), radiographic progression-free survival (RPFS) and time to PSA progression (TTPP); Pooled risk ratios (RR) for PSA response rate, objective response rate and adverse event were calculated. Results: Ten trials were included in the systematic review; Data of 2,283 patients (1,343 abiraterone; 940 placebo) from two phase 3 trials: COU-AA-301 and COU-AA-302 were meta-analyzed. Compared with placebo, abiraterone significantly prolonged OS (HR, 0.74; 95% confidence interval [CI], 0.66 to 0.84), RPFS (HR, 0.59; 95% CI, 0.48 to 0.74) and time to PSA progression (HR, 0.55; 95% CI, 0.43 to 0.70); it also significantly increased PSA response rate (RR, 3.63; 95% CI, 1.72 to 7.65) and objective response rate (RR, 3.05; 95% CI, 1.51 to 6.15). This meta-analysis suggested that the adverse events caused by abiraterone are acceptable and can be controlled. Conclutios: Abiraterone significantly prolonged OS, RPFS and time to progression patients with mCRPC, regardless of prior chemotherapy or whether chemotherapy-na$\ddot{i}$ve, and no unexpected toxicity was evident. Abiraterone can serve as a new standard therapy for mCRPC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6539-6540
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• 2012

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3443-3446
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• 2014

The aim of this study was to determine predictive factors for neutropenia after docetaxel-based systemic chemotherapy in patients with castration-resistant prostate cancer (CRPC). The study included 40 Korean CRPC patients who were treated with several cycles of docetaxel plus prednisolone from May 2005 to May 2012. Patients were evaluated for neutropenia risk factors and for the incidence of neutropenia. In this study, nine out of forty patients (22.5%) developed neutropenia during the first cycle of docetaxel-based systemic chemotherapy. Four experienced grade 2, three grade 3, and one grade 4 neutropenia. Multivariate analysis showed that pretreatment white blood cell (WBC) count (p=0.042), pretreatment neutrophil count (p=0.015), pretreatment serum creatinine level (p=0.027), and pretreatment serum albumin level (p=0.017) were significant predictive factors for neutropenia. In conclusion, pretreatment WBC counts, neutrophil counts, serum creatinine levels, and serum albumin levels proved to be significant independent risk factors for the development of neutropenia induced by docetaxel-based systemic chemotherapy in patients with CRPC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8177-8182
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• 2014

Background: Blocking angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling pathway to inhibit tumor growth has proven to be successful in treating a variety of different metastatic tumor types, including kidney, colon, ovarian, and lung cancers, but its role in castration-resistant prostate cancer (CRPC) is still unknown. We here aimed to determine the efficacy and toxicities of anti-VEGF agents in patients with CRPC. Materials and Methods: The databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to March 31, 2014 were searched for relevant articles. Pooled estimates of the objective response rate (ORR) and prostate-specific antigen (PSA) response rate (decline ${\geq}50%$) were calculated using the Comprehensive Meta-Analysis (version 2.2.064) software. Median weighted progression-free survival (PFS) and overall survival (OS) time for anti-VEGF monotherapy and anti-VEGF-based doublets were compared by two-sided Student's t test. Results: A total of 3,841 patients from 19 prospective studies (4 randomized controlled trials and 15 prospective nonrandomized cohort studies) were included for analysis. The pooled ORR was 12.4% with a higher response rate of 26.4% (95%CI, 13.6-44.9%) for anti-VEGF-based combinations vs. 6.7% (95%CI, 3.5-12.7%) for anti-VEGF alone (p=0.004). Similarly, the pooled PSA response rate was 32.4% with a higher PSA response rate of 52.8% (95%CI: 40.2-65.1%) for anti-VEGF-based combinations vs. 7.3% (95%CI, 3.6-14.2%) for anti-VEGF alone (p<0.001). Median PFS and OS were 6.9 and 22.1 months with weighted median PFS of 5.6 vs. 6.9 months (p<0.001) and weighted median OS of 13.1 vs. 22.1 months (p<0.001) for anti-VEGF monotherapy vs. anti-VEGF-based doublets. Conclusions: With available evidence, this pooled analysis indicates that anti-VEGF monotherapy has a modest effect in patients with CRPC, and clinical benefits gained from anti-VEGF-based doublets appear greater than anti-VEGF monotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6615-6619
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• 2015

Background: The expression of HER-2 in prostate cancer has been linked to disease progression. We analysed the presence of HER-2 expression in primary tumors in men undergoing radical prostatectomy, its association with clinical and pathological findings, and its expression in secondary circulating prostate cells (CPCs) during follow up, as well as links with biochemical failure and the effects of androgen blockade. Materials and Methods: Consecutive men undergoing radical prostatectomy for histologically confirmed prostate cancer were analyzed. HER-2 expression in the primary tumor was assessed using the HercepTest(R), CPCs were identified from blood samples using standard immunocytochemistry with anti-PSA and positive samples with the HercepTest(R) to determine HER-2 expression. The influence of HER-2 expression on the frequency of biochemical failure and effects of androgen blockade was determined. Results: 144 men with a mean age of $64.8{\pm}10.3$ years participated, with a median follow up of 8.2 years. HER-2 was expressed in 20.8% of primary tumors; it was associated with vascular infiltration and older age, but not with other clinical pathological findings. Some 40.3% of men had secondary CPCs detected, of which 38% expressed HER-2. Men CPC (+) had a higher frequency of biochemical failure, but there was no difference in HER-2 expression of CPCs with the frequency of biochemical failure. After androgen blockade, men with HER-2 (+) positive secondary CPCs had a higher frequency of disease progression to castrate resistant disease. Conclusions: HER-2 plays a dual role in the progression of prostate cancer; firstly it may increase the potential of tumor cells to disseminate from the primary tumor via the blood by increasing vascular infiltration. In the presence of androgens, there is no survival advantage of expressing HER-2, but once biochemical failure has occurred and androgen blockade started, HER-2 positive cells are resistant to treatment, survive and grow leading to castration resistant disease.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3645-3649
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• 2014

The aim of this study was to evaluate the efficacy of third-line combined androgen blockade (CAB) therapy for castration-resistant prostate cancer that relapsed after primary and second-line CAB. We retrospectively reviewed the medical records of 52 patients who received first-, second-, and third-line CAB therapy (medical or surgical castration, plus steroidal antiandrogen of chlormadinone acetate, or nonsteroidal antiandrogen of flutamide or bicalutamide). For cumulative analysis, we searched the PubMed database and identified a total of 50 cases published in English. Including our cases, this provided a total of 102 cases for analysis. In our study cohort, 11 cases (21.2%) achieved more than 50% reduction of serum prostate-specific antigen (PSA) on initiation of third-line CAB. We found that third-line CAB with nonsteroidal antiandrogen after second-line CAB with steroidal antiandrogen exhibited favorable results, with a positive response in six of 13 patients (46.2%). Cumulative analysis findings were comparable. Regarding the timing of third-line CAB administration, 15 patients had started at a PSA equal to or less than 4.0 ng/ml, and eight of them (53.3%) showed a positive response to treatment, compared to only three of 37 patients (8.1%) whose PSA at the initiation of third-line therapy was higher than 4.0 ng/ml (p<0.001). We conclude that third-line CAB with nonsteroidal antiandrogen would be particularly useful for patients whose cancer progressed after second-line CAB with steroidal antiandrogen. The timing of treatment seems to be important because the higher the PSA at the start of third-line therapy, the lower the PSA response rate.