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【Objective】 To observe the efficacy of abiraterone (AA) in the treatment of metastatic castration-resistant prostate cancer (mCRPC). 【Methods】 The clinical data of a newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) patient with high risk and high tumor load were analyzed. After operation and endocrine therapy, the disease evolution was observed. Relevant literature was reviewed. 【Results】 After laparoscopic radical prostatectomy, 6-month bicalutamide and androgen deprivation therapy (ADT), the total prostate specific antigen (tPSA) was reduced to the lowest of 0.51 ng/mL, and then increased month by month. After domestic abiraterone (trade name: Qingkeshu) in the 8th month was administered for 4 months, tPSA continued to increase to 12.39 ng/mL. The case was then diagnosed as mCRPC. The treatment was adjusted again in the 11th mouth and the patient received AA (trade name: Zeke) combined with prednisone and ADT, and tPSA decreased to 0.17 ng/mL 2 months later. After 14 months of treatment, tPSA remained at about 0.12 ng/mL. Systemic ECT examination indicated that the range of bone metastases decreased and some areas of nuclide concentration turned shallow without obvious adverse reactions. 【Conclusion】 AA combined with prednisone and ADT can produce rapid decline in PSA and a good response in mCRPC patients. It can also significantly slow the progression of bone metastasis and relieve pain symptoms without obvious adverse reactions. Long-term efficacy needs further observation.
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Resumen El cáncer de próstata metastásico resistente a la castración (CPRC) es una neoplasia heterogénea letal entre los hombres. 30% de los tumores acumulan errores deletéreos en genes implicados en la respuesta al daño del ADN (DNA damage response en inglés, DDR). Algunos de estos genes asociados a cáncer son BRCA 1 y BRCA 2. Mutaciones en estos genes favorecen la pérdida o la modificación de la función provocando un cambio permanente y transmisible, lo que conduce al desarrollo de cáncer de próstata agresivo. El objetivo del estudio fue identificar mediante secuenciación dirigida (Next-generation sequencing; NGS) variantes génicas de BRCA 1 y BRCA 2 en el genoma de pacientes con CPRC del Hospital Central Militar. Es importante destacar que los resultados demostraron una serie de alteraciones clínicas, así como una pérdida de la función de las proteínas relacionadas con mecanismos de reparación del ADN. Curiosamente, algunas de las variantes en el gen BRCA, de las que se informa aquí, son de significado incierto, lo que nos ha sido comunicado por primera vez.
Abstract Metastatic castration-resistant prostate cancer (CRPC) is a heterogeneous lethal neoplasm among men. 30% of tumors harbor deleterious errors in genes involved in the DNA damage response (DDR). Some of these cancer-associated genes are BRCA 1 and BRCA 2. Mutations to these genes favor loss or modification of function causing a permanent and transmissible change, leading to the development of aggressive prostate cancer. The aim of the study was to identify by Next-generation sequencing (NGS) BRCA 1 and BRCA 2 gene variants in peripheral blood of patients with CRPC at the Hospital Central Militar. Importantly, the results demonstrated a number of clinical alterations, as well as a loss of function of proteins related to DNA repair mechanisms. Interestingly, some of the variants in the BRCA gene, reported here, are of uncertain significance, which has been reported to us for the first time.
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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, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 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.
Subject(s)
Humans , Male , Abiraterone Acetate/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Androstenes , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dexamethasone/therapeutic use , Disease-Free Survival , Prednisone/therapeutic use , Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant/pathology , Retrospective Studies , Treatment OutcomeABSTRACT
DNA damage repair (DDR) defects occurred in 8%-16% of metastatic castration resistant prostate cancer (mCRPC). DDR gene mutation was related to poorer prognosis. Patients with DDR gene mutation, especially BRCA1/2 mutation, showed high sensitivity to poly ADP-ribose polymerase inhibitor (PARPi) and platinum.
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As the end-stage of prostate cancer, metastatic castration-resistant prostate cancer(mCRPC) complicates the disease and therefore challenges the doctors. In October 2018, an 87-year-old patient diagnosed with metastatic prostate cancer was admitted to Shanghai General Hospital for evaluation and treatment. Poor basic health condition plus severe side effect resulted in patient’s poor compliance with treatment and irregular follow-up. The patient progressed to mCRPC in September 2020, and was given enzalutamide as first-line therapy, after which the patient’s PSA level was under control with no side effect.
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Metastatic castration-resistant prostate cancer (mCRPC) is the inevitable form of most prostate cancers after endocrine therapy, and conventional drugs are not effective at this time.In this case, an elderly mCRPC patient with cardiopulmonary diseases admitted to the First Hospital of Shanxi Medical University in August 2020 was selected. After the failure of traditional endocrine therapy, enzalumide+ ADT regimen was adopted, and the patient's blood PSA was significantly reduced without cardiopulmonary adverse events.
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Background and Aims: CYP17 inhibitors can block androgen production both intratumorally and systemically, thus attenuating the progression of prostate cancer (PCa). Many randomized controlled trials (RCTs) showed promising results that men with metastatic castration-resistant PCa (mCRPC) might benefit from treatment with CYP17 inhibitors such as abiraterone acetate and orteronel. The goal of this study was to evaluate the efficacy of CYP17 inhibitors for the prognosis in patients with mCRPC. Materials and Methods: Studies were identified in PubMed/MEDLINE, the Cochrane Library, and the Web of Science. The RCTs with mCRPC patients focusing on the efficacy of CYP17 inhibitors were involved. Then, we analyzed the patients' prognosis such as overall survival (OS) and radiographic progression-free survival (RPFS). Results: A meta-analysis of the pooled data from seven randomized Phase III clinical trials was performed to compare 5516 mCRPC patients with CYP17 inhibitors versus that with placebo. Compared to placebo, the CYP17 inhibitors significantly increased the OS (pooled hazard ratios [HR]: 0.816, 95% confidence interval [CI]: 0.750–0.887), RPFS (pooled HR: 0.647, 95% CI: 0.557–0.752), and time to prostate-specific antigen (PSA) progression (pooled HR: 0.599, 95% CI: 0.517–0.693). Additional endpoints such as PSA response rate, objective response assessed by Response Evaluation Criteria in Solid Tumors, and time to initiation of chemotherapy were included in this study and were found having significant improvement with CYP17 inhibitors compared to placebo. Conclusion: This research showed that CYP17 inhibitors had a significant improvement on prognosis of patients with mCRPC within a relative safety profile both in pre- and post-chemotherapy trials. These expected results provide evidence for the use of CYP17 inhibitors to treat mCRPCs
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PURPOSE: The aim of this study was to evaluate safety and therapeutic efficacy of lutetium 177 prostate-specific membrane antigen (Lu-177-PSMA) in metastatic castration-resistant prostate cancer (mCRPC) patients with low performance status.METHODS: Twenty-two patients already treated with anti-androgens and docetaxel were enrolled for one cycle of Lu-177-PSMA therapy. Haemoglobin, total leukocyte counts, platelets and serum creatinine for toxicity profile while prostate specific antigen (PSA), Eastern Cooperative Oncology Group (ECOG) performance status, visual analogue scale (VAS) and analgesic quantification scale (AQS) for therapeutic efficacy were recorded pre and 8 weeks post therapy. Wilcoxon signed-rank and ANOVA tests were used for statistical analysis.RESULTS: Partial response (PR), stable disease (SD) and progressive disease (PD) for PSAwere seen in 5 (22.7%), 13 (59.1%) and 4 (18.2%) patients respectively treated with mean 6.88 GBq dose of Lu-177-PSMA. 8/22 (36.4%) patients showed ≥ 30% drop in PSA. Grade 3 haemoglobin toxicity was seen in 5/22 (22.7%) patients. No patient developed grade 4 haemoglobin toxicity. No patients had grade 3 or 4 leukocytopenia or thrombocytopenia. Wilcoxon signed-rank test showed statistical significant (P < 0.05) difference in pre and post treatment ECOG, VAS, and AQS scores. The ANOVA test showed statistically significant difference in mean doses of Lu-177-PSMA used in three PSA response groups while difference was non-significant for other variables.CONCLUSION: We concluded that Lu-177-PSMA therapy has adequate pain palliation in end-stage mCRPC patients with low performance status and it has a potential to become effective therapeutic option in properly selected patients.
Subject(s)
Humans , Creatinine , Leukocyte Count , Leukopenia , Lutetium , Membranes , Prostate , Prostate-Specific Antigen , Prostatic Neoplasms , ThrombocytopeniaABSTRACT
Objective • To determine whether pre-treatment prognostic nutritional index (PNI) level and its variation can predict the primary resistance to abiraterone (AA) and the prognosis in metastatic castration-resistant prostate cancer (mCRPC) patients treated with AA. Methods • A total of 112 mCRPC patients treated with AA were included in Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine. PNI levels were measured before and one month after AA treatment. PNI was calculated from preoperative laboratory parameters using the formula [10×serum albumin level (g/dL) + 0.005×lymphocyte count (per μL) in the peripheral blood]. Univariate and multivariate Logistic regression analyses were used to identify predictive factors of initial efficacy to AA treatment. Univariable and multivariable Cox regression analyses were performed to determine the prognostic factors that were associated with prostate-specific antigen (PSA) progression-free survival (PSA-PFS), radiographic PFS (rPFS) and overall survival (OS). Results • Eighty-one of all 112 (72.3%) patients showed initial response to AA treatment, and 15 patients experienced PSA flare during AA treatment. In multivariate Logistic regression analysis, the high baseline PNI level, the decrease of PSA level during the first month of AA treatment and the elevation of PNI level during the first month of AA treatment were significantly correlated with the initial response to AA treatment. In multivariate Cox regression analyses, the low baseline PNI level remained significant predictor of OS, rPFS and PSA-PFS.Conclusion • Independent of PSA level variation, the elevation of PNI level during the first month of AA treatment and high baseline PNI level are significantly correlated with the initial response to AA treatment. In addition, low baseline PNI level is a negative independent prognosticator of survival outcomes in mCRPC patients treated with AA.
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Objective To investigate the dose of docetaxel appropriate for patients with metastatic castration-resistant prostate cancer and its affects to the prognosis.Methods A retrospective analysis was performed on the clinical data of 75 patients with metastatic castration-resistant prostate cancer admitted from March 2010 to July 2016 who received docetaxel combined with prednisone chemotherapy.The patients were divided into the low-dose group (n =43,docetaxel ＜ 65 mg/m2),the middle-dose group (n =21,docetaxel 65-70 mg/m2) and the high-dose group (n =11,docetaxel ＞ 70 mg/m2).The median age in the low-dose group,middle-dose group and high-dose group was 67 (53-80),66 (56-78) and 61 (47-76) years old,respectively.Among 75 patients with bone metastasis,2 patients had no evidence of bone metastasis in the low-dose group.The lymph node metastasis was found in 26,13 and 6 cases in each group,respectively.And visceral and other metastasis were founded in 11,4 and 2 cases,respectively.The Gleason score in the low-dose group was≤7 points in 15 cases,≥8 points in 22 cases and no score in 6 cases.The Gleason score inthe middle-dose group was ≤7 points in 4 cases,≥8 points in 13 cases and no score in 4 cases.The Gleason score in the high-dose group was ≤7 points in 3 cases,≥8 points in 5 cases and no score in 3 cases.The number of patients with pain in the low-dose group,middle-dose group and high-dose group was 36,12 and 9,respectively,there were no significant differences in the above indicators (P ＞ 0.05),except age,which showed relatively more aged patients in the low-dose group,(P =0.045).Kaplan-Meier method was used to compare the overall survival (OS),progression-free survival (PFS) and the incidence of ≥CTCAE-4 grade 3 adverse reactions between the two groups.The Cox regression model was adopted to analyzed the factors that might affect patient prognosis,including the effective time of first-line endocrine therapy,hemoglobin level,ECOG score,pain score,number of cycles of chemotherapy,age,dose of docetaxel and alkaline phosphatase (ALP).Kaplan-Meier method was used to analyze the effect of dose of docetaxel on the prognosis,and log-rank method was used to test the significance of the results.Results The median OS was respectively 24.1,18.5 and 23.5 months in the low-dose group,middle-dose group and high-dose group,respectively.The median PFS was 5.3 months in all three groups,which didn't show statistically significant differences.The incidence of grade 3/4 adverse reactions in the low-dose group,middle-dose group and high-dose group was 15 cases (34.9％),8 cases (38.1％) and 5 cases (45.5％) respectively.It showed an increasing trend,but no statistically significant difference.The single factors related to OS mainly include the effective time of first-line endocrine therapy,hemoglobin level,ECOG score,pain score,number of cycles of chemotherapy,there was no significant correlation with age,docetaxel dose,ALP and PSA value.Conclusions It is common to receive lower doses of docetaxel in clinical practice for patients with metastatic castration-resistant prostate cancer in China.The efficacy of low-dose docetaxel is similar to that of high doses (standard dosage).There was no significant correlation between the OS and the actual dose of docetaxel in the tolerable range.
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Prostate cancer is cancer of the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, some grow relatively quickly. The cancer cells may spread from the prostate to other area of the body, particularly the bones and lymph nodes. Factors that increase the risk of prostate cancer include older age, a family history of the disease, and race. About 99% of cases occur in males over the age of 50. Clinical features include hematuria, dysuria (painful urination),nocturia(urination at night). Lower blood levels of vitami D may increase the risk of developing prostate cancer. Infection with the sexually transmitted diseases, chlamydia, gonorrhea, syphilis and prostatitis seem to increase risk of prostate cancer. Diagnosis can be confirmed by digital rectal examination (DRE) with prostate-specific antigen (PSA) blood test, cystoscopy, transrectal ultrasonography and biopsy (The removal of small pieces of the prostate for microscopic examination). Medicines like 5-alpha-reductase inhibitors (finasteride and dutasteride) reduce the overall risk of prostate cancer. Apalutamide, sold under the brand name Erleada, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is specifically indicated for use in conjunction with castration in the treatment of non-metastatic castration-resistant prostate cancer (NM-CRPC). It is taken by mouth. Apalutamide was first described in 2007 and was approved for the treatment of prostate cancer in February 2018. Apalutamide is used in conjunction with castration, either via bilateral orchiectomy or gonadotropin-releasing hormone analogue (GnRH analogue) therapy, as a method of androgen deprivation therapy in the treatment of non-metastatic castration-resistant prostate cancer (NM-CRPC).
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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.
Subject(s)
Humans , Male , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , Docetaxel/therapeutic use , History, 20th Century , History, 21st Century , Neoadjuvant Therapy , Prostatic Neoplasms/surgery , Taxoids/therapeutic useABSTRACT
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.
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Objective To evaluate the efficacy and safety of the modified docetaxel plus prednisone scheme for the metastatic castration resistant prostate cancer patients who got poor tolerance to chemotherapy.Method The clinical data of 50 metastatic castration resistant prostate cancer who received docetaxel + prednisone chemotherapy from March 2010 to October 2015 were analyzed retrospectively.23 cases received the modified DP regimen (modified group),27 cases received the standard DP regimen (standard group).The median age of the modified group and the standard group were 69 years (47-80 years) and 63 years (52-77 years) (P =0.005).There were 19 and 24 cases with pain in modified group and standard group respectively;10 and 19 cases with lymph node metastasis respectively;3 and 4 cases of visceral metastasis respectively;all of the 50 patients were complicated with bone metastasis.For the pathological Gleason score,there were 7 cases scored ≤7 points,13 cases scored ≥ 8 points and 3 cases unscored in the modified group;7 cases scored ≤7 points,15 cases scored ≥8 points and 5 cases unscored in standard group.There was no significant difference of the pain,metastasis,and Gleason score between the two groups (P ＞ 0.05).Progression free survival (PFS),overall survival (OS)and adverse events were analyzed using Kaplan-Meier curves,and the differences were assessed using the log-rank test.Results In the modified group and standard group,the median follow-up times were 11.0 months and 14.0 months respectively,the median chemotherapy cycles were 4.5 cycles and 5.0 cycles respectively;OS were 18.0 months and 27.5 months respectively (P =0.746).The PFS of the two groups were 6.0 months and 5.2 months,respectively (P =0.822).The PSA response were 13 cases and 17 cases in the modified group and standard group respectively (P =0.615),and the pain response were 8 cases and 7 cases (P =0.927),grade 3 to 4 adverse events were 3 cases and 14 cases (P =0.003).The main adverse events were blood toxicity,neutrophils,gastrointestinal reaction,edema,fatigue and oral mucositis etc.Conclusions Compared with the standard DP scheme,the modified DP scheme had no significant difference in OS,PFS,pain response rate and PSA response rate,while the incidence of grade 3 to 4 adverse events was significantly reduced.Modified DP scheme may be a better choice for patients with metastatic castration resistant prostate cancer who get poor tolerance to chemotherapy.
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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.
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Objective· To assess the efficacy of abiraterone acetate (AA) plus prednisone treating metastatic castration-resistant prostate cancer (mCRPC) patients and analyze the prognostic factors for this treatment. Methods · The medical history of 112 patients with mCRPC treated in Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine, including 70 patients in the chemotherapy-na?ve setting and 42 in the post-chemotherapy setting, were retrospectively reviewed. Coprimary end points were prostate specific antigen progression-free survival (PSA PFS), radiographic PFS (rPFS) and overall survival (OS). Univariable and multivariable Cox analyses were performed to determine prognostic factors that were associated with PSA PFS, rPFS and OS. Results · At a median follow-up of 20.2 months, 59 (52.7%) patients had died. The median PSA PFS, rPFS and OS were 8.9 (7.8~10.0) months, 9.7 (9.0~10.4) months, and 22.2 (20.3~24.1) months, respectively. In multivariate analysis, previous chemotherapy, neutrophil lymphocyte ratio(≥3 vs<3),serum lactate dehydrogenase level(≥196 U/L vs<196 U/L)and ECOG PS(≤?1 vs 2)were independent predictors for PSA PFS and rPFS,and previous chemotherapy,ECOG PS(≤?1 vs 2)remained significant predictors for OS. Conclusion·These results further support the favourable profile of AA plus prednisone in patients with mCRPC in China.Previous chemotherapy,ECOG PS(≤?1 vs 2)remained significant predictors for OS.