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Predictors of efficacy of corticosteroid switching from abiraterone plus prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer

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Asian Journal of Andrology 2022年第2期24卷 154-160页

作者： Yu-Chao Ni Jin-Ge Zhao Meng-Ni Zhang Yi-Jun Zhang Zhen-Yu Yang Ni Chen Jun-Ru Chen Peng-Fei Shen Guang-Xi Sun Xing-Ming Zhang Yong-Hong Li Hao Zeng Department of Urology Institute of UrologyWest China HospitalSichuan UniversityChengdu 610041China Department of Pathology West China HospitalSichuan UniversityChengdu 610041China Department of Pathology Sun Yat-Sen University Cancer CenterGuangzhou 510060China Department of Urology Sun Yat-Sen University Cancer CenterGuangzhou 510060China

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer(mCRPC).Here,we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate(AA).We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University cancer Center between January 2016 and December 2018.All cases received AA plus prednisone as first-line therapy during mCRPC.Primary end points were biochemical progression-free survival(bPFS)and overall survival(OS).The risk groups were defined based on multivariate analysis.A total of 42(41.6%)and 25(24.8%)patients achieved 30%and 50%decline in prostate-specific antigen(PSA),respectively,after corticosteroid switching.The median bPFS and median OS on AA plus dexamethasone were 4.9(95%confidence interval[CI]:3.7–6.0)months and 18.8(95%CI:16.2–30.2)months,respectively.Aldo-keto reductase family 1 member C3(AKR1C3)expression(hazard ratio[HR]:2.15,95%Cl:1.22–3.80,P=0.008)and baseline serum alkaline phosphatase(ALP;HR:4.95,95%Cl:2.40–10.19,P160 IU l−1(HR:3.41,95%Cl:1.57–7.38,P=0.002)together with PSA level at switch≥50 ng ml−1(HR:2.59,95%Cl:1.22–5.47,P=0.013)independently predicted poorer OS.Based on the predictive factors in multivariate analysis,we developed two risk stratification tools to select candidates for corticosteroid switching.Detection of serum ALP level,PSA level,and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.

关键词： abiraterone acetate alkaline phosphatase corticosteroid switching dexamethasone metastatic castration-resistant prostate cancer

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The safety of radium-223 combined with new-generation hormonal agents in bone metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis

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Asian Journal of Andrology 2023年第4期25卷 441-447页

作者： Ming-Hao Wang Jin-Dong Dai Xing-Ming Zhang Jin-Ge Zhao Guang-Xi Sun Yu-Hao Zeng Hong Zeng Nan-Wei Xu Hao Zeng Peng-Fei Shen Department of Urology West China Hospital of Sichuan UniversityChengdu 610041China

Patients with bone metastatic castration-resistant prostate cancer (mCRPC) might benefit from radium-223 (^(223)Ra) combined withnew-generation hormonal agents (NHAs) in terms of survival and quality of life (QoL). However, the safety of combination therapiesremains unclear. Therefore, we aimed to perform a network meta-analysis by reviewing the literature about the combination of^(223)Ra with abiraterone acetate plus prednisone (AAP) or enzalutamide and to evaluate the safety of combination therapy in bonemCRPC patients. Ultimately, ten studies (2835 patients) were selected, including four randomized controlled trials (RCTs), fiveretrospective cohort studies, and one single-arm study. Overall, there was no difference in the incidence of fracture between the^(223)Ra+NHA combination group and the ^(223)Ra monotherapy group (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 0.91–2.34,P = 0.66), but the incidences in both the ^(223)Ra+NHA combination group (OR: 3.22, 95% CI: 2.24–4.63, P < 0.01) and the ^(223)Ramonotherapy group (OR: 2.24, 95% CI: 1.23–4.08, P < 0.01) were higher than that in the NHA monotherapy group. However, inthe meta-analysis involving only RCTs, there was no difference between the ^(223)Ra monotherapy group and the NHA monotherapygroup (OR: 1.14, 95% CI: 0.22–5.95, P = 0.88), while the difference between the ^(223)Ra+NHA combination group and the NHAmonotherapy group remained significant (OR: 3.22, 95% CI: 2.24–4.63, P < 0.01). Symptomatic skeletal events (SSEs), SSE-freesurvival (SSE-FS), all grades of common adverse events (AEs), and ≥grade 3 AEs among all groups did not show any significantdifference. Our results indicate that the combination of ^(223)Ra with NHAs was well tolerated in bone mCRPC patients compared to ^(223)Ra monotherapy, even though the incidence of fracture was higher in patients who received ^(223)Ra than that among those whoreceived NHA monotherapy. More evidence is needed to explore the safety and efficiency of ^(223)Ra combination therapies.

关键词： meta-analysis metastatic castration-resistant prostate cancer new-generation hormonal agents radium-223 safety

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Radium-223 in metastatic castration resistant prostate cancer

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Asian Journal of Andrology 2014年第3期16卷 348-353页

作者： Winston Vuong Oliver Sartor Sumanta K Pal Department of Medical Oncology and Experimental Therapeutics City of Hope Comprehensive Cancer Center Duarte CA Department of Medicine Tulane University School of Medicine New Orleans LA USA

In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer （mCRPC）. For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival benefit in phase III studies. These agents include sipuleuceI-T, cabazitaxel, abiraterone, enzalutamide and （most recently） radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer （e.g. samarium-153 and strontium-89）, radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors influencing clinical implementation.

关键词： alpharadin bone metastases metastatic castration-resistant prostate cancer radiopharmaceuticals radium-223 Xofigo

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Indirect comparison between abiraterone acetate and enzalutamide for the treatment of metastatic castration-resistant prostate cancer： a systematic review

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Asian Journal of Andrology 2017年第2期19卷 196-202页

作者： Wei Zhang Teng-Yun Wu Qi Chen Xiao-Lei Shi Guang-An Xiao Lin Zhao Chuan-Liang Xu Tie Zhou Ying-Hao Sun Department of Urology Changhai Hospital Second Military Medical University Shanghai China Air Force General Hospital of Chinese People's Liberation Army Beijing China Department of Health Statistics Faculty of Health Service Second Military Medical University Shanghai China

This study was designed to evaluate the efficacy, tolerability, and sequential administration of abiraterone acetate （AA） and enzalutamide （Enz） for metastatic castration-resistant prostate cancer （mCRPC）. A literature search was performed with PubMed, Embase, and Web of Science databases to identify relevant studies. Reviewed literature included published phase III trials of AA or Enz in mCRPC and studies regarding their sequential administration. Given the difference in control arms in AA （active comparator） and Enz （true placebo） randomized phase III studies, indirect comparisons between AA and Enz in mCRPC showed no statistically significant difference in overall survival in prechemotherapy and postchemotherapy settings （HR. 0.90, 95% CI, 0.73-1.11; HR： 0.85, 95% CI, 0.68-1.07）. Compared with AA, Enz may better outperform control arms in treating mCRPC both before and after chemotherapy regarding secondary endpoints based on indirect comparisons： time to prostate-specific antigen （PSA） progression （HR. 0.34, 95% CI, 0.28-0.42; HR： 0.40, 95% CI, 0.30-0.53）, radiographic progression-free survival （HR： 0.37, 95% CI, 0.28-0.48; HR： 0.61, 95% CI, 0.50-0.74）, and PSA response rate （OR： 18.29, 95% CI, 11.20-29.88; OR： 10.69, 95% CI, 3.92-29.20）. With regard to the effectiveness of Enz following AA or AA following Enz, recent retrospective case series reported overall survival and secondary endpoints for patients with mCRPC progression after chemotherapy. However, confirmatory head-to-head trials are necessary to determine the optimal sequencing of these agents.

关键词： abiraterone acetate enzalutamide indirect comparison metastatic castration-resistant prostate cancer sequential therapy

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Surface-enhanced Raman spectroscopy of serum predicts sensitivity to docetaxel-based chemotherapy in patients with metastatic castration-resistant prostate cancer

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Journal of Innovative Optical Health Sciences 2021年第4期4卷 82-93页

作者： Jianian Hu Xiaoguang Shao Chenfei Chi Yinjie Zhu Zhixiang Xin Jianjun Sha Baijun Dong Jiahua Pan Wei Xue Department of Urology Ren Ji Hospital School of Medicine Shanghai Jiao Tong UniversityShanghaiP.R.China

Docetaxel-based chemotherapy,as the first-line treatment for metastatic castration-resistant prostate cancer(mCRPC),has succeeded in helping quite a number of patients to improve quality of life and prolong survival time.However,almost half of mCRPC patients are not sensitive to docetaxel chemotherapy initially.This study aimed to establish models to predict sensitivity to docetaxel chemotherapy in patients with mCRPC by using serum surface-enhanced Raman spectroscopy(SERS).A total of 32 mCPRC patients who underwent docetaxel chemo-therapy at our center from July 2016 to March 2018 were included in this study.Patients were dichotomized in prostate-specific antigen(PSA)response group(n=17)versus PSA failure group(n=15)according to the response to docetaxel.In total 64 matched spectra from 32 mCRPC patients were obtained by using SERS of serum at baseline(q0)and after 1 cycle of docetaxel chemotherapy(ql).Comparing Raman peaks of serum samples at baseline(q0)be-tween two groups,significant differences revealed at the peaks of 638,810,890(p<0.05)and 1136cm^(-1)(p<0.01).The prediction models of peak 1363 cm^(-1)and principal component anal-ysis and linear discriminant analysis(PCA-LDA)based on Raman data were established,re-spectively.The sensitivity and specificity of the prediction models were 71%,80%and 69%,78%through the way of leave-one-out cross-validation.According to the results of five-cross-valida-tion,the PCA-LDA model revealed an accuracy of 0.73 and AUC of 0.83.

关键词： surface-enhanced Raman spectroscopy metastatic castration-resistant prostate cancer docetaxel sensitivity of chemotherapy

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Comparative analysis of the effectiveness of abiraterone before and after docetaxel in patients with metastatic castration-resistant prostate cancer

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World Journal of Clinical Oncology 2015年第4期6卷 64-72页

作者： Raji Shameem Muhammad Saad Hamid Kevin Y Xu Shenhong Wu Department of Hematology/Oncology Fox Chase Cancer Center Department of Internal Medicine Detroit Medical Center/Wayne State University Department of Medical Education Icahn School of Medicine at Mount Sinai Division of Hematology/Oncology Department of MedicineStony Brook University School of Medicine Northport VA Medical Center

AIM: To study the efficacy and safety of abiraterone in patients with and without prior chemotherapy.METHODS: The databases including Pub Med and abstracts presented at the American Society of Clinical Oncology meetings up to April 2014 were systematically searched. Eligible studies included randomized controlled trials(RCTs) in which abiraterone plus prednisone was compared to placebo plus prednisone in metastatic castration-resistant prostate cancer(CRPC) patients. The summary incidence, relative risk, hazard ratio and 95%CI were calculated using random or fixed-effects models. Heterogeneity test was performed to test between-study differences in efficacy and toxicity.RESULTS: A total of two phase III RCTs were included in our analysis, with metastatic CPRC patients before(n = 1088) and after chemotherapy(n = 1195). Prior chemotherapy did not significantly alter the effect of abiraterone on overall survival(P = 0.92) and prostatespecific antigen(PSA) progression-free survival(P = 0.13), but reduced its effect on radiographic-prog-ression-free survival(P = 0.04), objective response rate(P metastatic CRPC.

关键词： Abiraterone Docetaxel metastatic castration-resistant prostate cancer Chemotherapy-naïve Pre-chemotherapy Post-chemotherapy

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Comprehensive treatment for metastatic castration-resistant prostate cancer with neuroendocrine differentiation:a case report

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cancer Advances 2023年第23期6卷 1-5页

作者： Zeng-Feng Han Bin-Xu Sun Tian-Qi Chen Jin-Ming Liu Jun-Qi Sun Ya-Di Shi Rui-Yu Mou Shan-Qi Guo Department of Oncology The First Teaching Hospital of Tianjin University of Traditional Chinese MedicineNational Clinical Research Center for Chinese Medicine Acupuncture and MoxibustionTianjin 300381China

Retrospective analysis of the progression of a case of metastatic castration-resistant prostate cancer with neuroendocrine differentiation:the patient was a 65 year old man with prostate adenocarcinoma on prostate biopsy,Gleason 4+4 score=8,70%,ISUP4 group,localized invasion of nerves.Progressed to metastatic castration-resistant prostate cancer after 8 months of novel endocrine therapy,persistent elevated PSA after endocrine therapy,chemotherapy,and radiation,abdominal metastasis,brain metastasis,gastric metastasis,and staging as neuroendocrine differentiation after second prostate biopsy,which is a highly malignant subtype and has been concerned as a mechanism of resistance to targeted therapies.We discuss how to choose a more optimal treatment plan and outline the patient's diagnostic and therapeutic course.We provide a reflection for the clinical study of metastatic castration-resistant prostate cancer with neuroendocrine type.

关键词： metastatic castration-resistant prostate cancer neuroendocrine differentiation neoplasm drug resistance distant metastasis secondary puncture

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Tousled-like kinase 1:a novel factor with multifaceted role in mCRPC progression and development of therapy resistance

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cancer Drug Resistance 2022年第1期5卷 93-101页

作者： Md Imtiaz Khalil Arrigo De Benedetti Department of Biochemistry and Molecular Biology LSU Health Sciences CenterShreveportLA 71103USA

Standard treatment for advanced prostate cancer(PCa)consists of androgen deprivation therapy(ADT),but ultimately fails,resulting in the incurable phase of the disease:metastatic castration-resistant prostate cancer(mCRPC).Targeting PCa cells before their progression to mCRPC would greatly improve the outcome,if strategies could be devised selectively targeting androgen receptor(AR)-dependent and/or independent compensatory pathways which promote mCRPC development.Combination therapy by targeting the DNA damage response(DDR)along with ADT has been limited by general toxicity,and a goal of clinical trials is how to target the DDR more specifically.In recent years,our lab has identified a key role for the DDR kinase,TLK1,in mediating key aspects of adaptation to ADT,first by promoting a cell cycle arrest(through the TLK1>NEK1>ATR>Chk1 kinase cascade)under the unfavorable growth conditions(androgen deprivation),and then by reprogramming the PCa cells to adapt to androgen-independent growth via the NEK1>YAP/AR>CRPC conversion.In addition,TLK1 plays a key anti-apoptotic role via the NEK1>VDAC1 regulation on the intrinsic mitochondrial apoptotic pathway when the DDR is activated.Finally,TLK1 was recently identified as having an important role in motility and metastasis via regulation of the kinases MK5/PRAK and AKT(indirectly via AKTIP).

关键词： TLK1 NEK1 YAP1 VDAC1 DNA damage response prostate cancer metastatic castration-resistant prostate cancer drug resistance in mCRPC

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Early prostate specific antigen decline and its velocity are independent predictive factors for outcomes of mCRPC patients treated with abiraterone acetate

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Military Medical Research 2022年第6期9卷 754-756页

作者： Jiang-Yi Wang Guo-Peng Yu Long Li Guo-Wen Lin Ding-Wei Ye Department of Urology Fudan University Shanghai Cancer Center270 Dong'an RoadShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of Urology Shanghai Ninth People's HospitalShanghai Jiaotong University School of MedicineShanghai 200011China

Dear Editor,Although the incidence of prostate cancer(PCa) has decreased in recent decades in Western countries, it has gradually increased in China due to the increasingly longer life expectancy and more popular west... 详细信息

关键词： metastatic castration-resistant prostate cancer PSA decline PSA velocity Overall survival Time to PSA progression

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Role of chemotherapy in prostate cancer

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Asian Journal of Andrology 2018年第3期20卷 221-229页

作者： Rita Nader Joelle El Amm Jeanny B Aragon-Ching Department of Internal Medicine Lebanese American University Beirut 1102 2801 Lebanon Department of Internal Medicine Division of Hematology and Oncology Lebanese American University Beirut 1102 2801 Lebanon Genitourinary Medical Oncology Inova Schar Cancer Institute Fairfax VA 22031 USA

Chemotherapy in prostate cancer （PCa） has undergone dramatic landscape changes. While earlier studies utilized varying chemotherapy regimens which were found to be largely palliative in nature and hardly resulted in durable or meaningful responses, docetaxel resulted in the first chemotherapy agent that showed improvement in overall survival in metastatic castration-resistant prostate cancer （mCRPC）. However, combination chemotherapy or any agents added to docetaxel have failed to yield incremental benefits. The improvement in overall survival as well as secondary endpoints of prostate-specific antigen （PSA） and time to recurrence when using docetaxel in the metastatic hormone-sensitive state has changed the standard of care for treatment of newly diagnosed de novo metastatic PCa. There are also promising results in locally advanced PCa and high-risk PCa in both the neoadjuvant and adjuvant settings. This review summarizes the historical as well as the more contemporary use of chemotherapeutic agents in PCa in varying states and phases of disease.

关键词： docetaxel metastatic castration-resistant prostate cancer prostate cancer

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