Efficacy of docetaxel-based chemotherapy following ketoconazole in metastatic castration-resistant prostate cancer: Implications for prior therapy in clinical trials

ObjectivesAbiraterone acetate (AA) is a CYP17 inhibitor of androgen synthesis approved for use following docetaxel for metastatic castration-resistant prostate cancer (mCRPC); evaluation in the pre-docetaxel setting is ongoing. Given that the reported efficacy of AA is lower following docetaxel vs. pre-docetaxel, the potential exists for cross resistance given docetaxel's partly androgen receptor targeting activity. The efficacy of docetaxel following ketoconazole (KC), a weaker and nonspecific inhibitor of CYP17, may provide some insights into this potential interaction. We retrospectively evaluated the efficacy of every 3-week docetaxel with prednisone (DP) in mCRPC previously exposed to KC compared to KC-naive patients.Materials and methodsA randomized phase II trial of men with mCRPC treated with DP + AT-101 (bcl-2 inhibitor) vs. DP plus placebo was analyzed. Both arms were combined for analysis as no significant differences were seen. Overall survival (OS), progression-free survival (PFS), objective response (ORR), pain, and prostate-specific antigen (PSA) response rates were estimated with and without prior KC. Cox proportional hazards regression models were used to estimate the effect of covariates on OS.ResultsOf 220 evaluable men, 40 (18.2%) received prior KC. The median OS with DP-based therapy of KC-naive patients (18.3 months, 95% CI: 15.0, 24.5) and post-KC patients (17.0 months, 95% CI: 9.9, 20.4) was not statistically different (P = 0.20). After controlling for prognostic classifications, analyses demonstrated consistent trends for worsening of OS after KC, with (hazard ratios (HRs) 1.33–1.46. Similar unfavorable trends were observed for ORR, PSA declines, and PFS.ConclusionsIn this hypothesis-generating analysis, patients treated with docetaxel-based chemotherapy following prior KC had numerically and consistently worse outcomes than patients not exposed to prior KC. Although the estimated differences did not attain statistical significance, evaluation of outcomes with docetaxel in particular, and all classes of novel and emerging agents following AA, is of clinical importance, given its more potent androgen synthesis inhibition compared with KC. Drug development should take into account the potential impact of previous therapy.     

PSA time to nadir as a prognostic factor of first-line docetaxel treatment in castration-resistant prostate cancer: Multicenter validation in patients from the Chinese Prostate Cancer Consortium

ObjectiveDocetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China. We have previously shown that time to nadir (TTN) of prostate-specific antigen (PSA) is an important prognostic factor in patients from a single center in Northwestern China. In this study, we performed a multicenter validation of the prognostic role of TTN in additional Chinese patients with mCRPC receiving docetaxel treatment.Materials and methodsThe data were gathered from 170 eligible Chinese patients who received docetaxel chemotherapy from January 2007 to October 2018 in 11 Chinese Prostate Cancer Consortium member hospitals in China. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS) and progression-free survival (PFS).ResultsPatients with a TTN ≥ 15 weeks had a longer OS and PFS compared to those with a TTN < 15 weeks (43 vs. 15 months, P < 0.001; 24 vs. 6 months, P < 0.001, respectively). In addition, Patients with a TTN ≥ 15 weeks and PSA nadir <4.55ng/ml were associated with longer OS than others (HR 0.093, 95% CI 0.044-0.188, P < 0.001; HR 4.002, 95% CI 1.890–8.856, P = 0.001, respectively) and TTN, PSA nadir, PSA baseline (optimal threshold 56.07 ng/ml), and PSA reduction (optimal threshold 50%) were associated with PFS (HR 0.238, 95% CI 0.149–0.382, P < 0.001; HR 1.676, 95% CI 1.033–2.722, P = 0.037; HR 1.770, 95% CI 1.134–2.763, P = 0.012; HR 0.573, 95% CI 0.428–0.756, P < 0.001; respectively). Furthermore, patients with a PSA nadir <4.55 ng/ml had longer OS and PFS compared to other patients when TTN was ≥15 weeks.ConclusionIn this multicenter validation study, TTN and PSA nadir remain important prognostic markers in predicting therapeutic outcomes in Chinese men who receive chemotherapy for mCRPC.     

The efficacy of abiraterone acetate in treating Taiwanese chemo-refractory metastatic castration-resistant prostate cancer patients

ObjectiveTo evaluate the efficacy of abiraterone acetate in combination with prednisolone in Taiwanese men with metastatic castrate-resistant prostate cancer (mCRPC) who failed docetaxel-based chemotherapy.Materials and methodsIn this single-arm, open label study, 30 mCRPC patients with prostate specific antigen (PSA) progression after docetaxel chemotherapy were enrolled. All patients were treated with abiraterone acetate 1000 mg once daily and prednisolone 5 mg twice daily. The primary end-point was PSA response rate (defined as proportion of patients achieving a PSA decline of ≥50%). Secondary end-points were overall survival and time-to-PSA progression.ResultsAmong 28 patients who received one or more cycles of treatment, 15 (53.6%) men achieved PSA response [95% confidence interval (CI) 33.9–72.5]. The median time-to-PSA progression was 5.5 months (95% CI 3.1–7.9). The median interval from stopping abiraterone to death was 3.4 months (95% CI 0.1–21.0), and the median overall survival was 19.2 months (95% CI 13.0–25.4). The PSA responders had better overall survival compared with PSA nonresponders, in both univariate (log rank test, p = 0.007) and multivariate (Cox regression, p = 0.001; relative risk: 0.31; 95% CI: 0.12–0.76) analysis. Both a high Gleason score (≥8) and viscera involvement did not have an unfavorable response to abiraterone treatment.ConclusionA combination of abiraterone acetate and prednisolone can improve the overall survival in Taiwanese mCRPC patients who fail prior docetaxel chemotherapy.     

Efficacy of cabazitaxel in fourth or later line of therapy in metastatic castration-resistant prostate cancer: Multi-institutional real-world experience in Germany

ObjectiveSince multiple oncological treatment options in metastatic castration-resistant prostate cancer (mCRPC) are available, optimal sequencing of therapies are under investigation. However, the efficacy of Cabazitaxel (CAB) in fourth and later lines of therapy is rarely investigated.Material and MethodsFifty three patients with mCRPC treated with CAB in fourth line or later were included in our retrospective study, which involved eight uro-oncology centers in Germany. Clinical and tumor characteristics, as well as PSA-response rates were analyzed. Kaplan-Meier plots addressed overall survival (OS) and progression-free survival (PFS). Logistic regression models predicted risk factors of overall mortality (OM).ResultsOf 53 patients, 79% (n=42), 19% (n=10) and 2% (n=1) received CAB in fourth, fifth and sixth line. A median of 4 cycles of CAB were administered. Median PSA at start of CAB was 199ng/ml (interquartile range (IQR) 70-869). In total, 89% had bone and 40% visceral metastases prior to the start of CAB. Moreover, 30% of patients received Docetaxel in first line therapy for mCRPC. Most frequent sequence of therapy was abiraterone followed by docetaxel and followed by enzalutamide. Overall, median PSA-response rate was -20% (IQR -80 to +10%). Patients with docetaxel in first line had a significantly better median PSA-response on CAB (-80 vs. 20%, P=0.03). Median OS, radiographic PFS and overall PFS were 14.8 (Confidence interval (CI): 11.0–20.8), 3.0 (CI: 2.9–4.0) and 2.9 (CI: 2.0–3.3) months, respectively. In multivariable analyses, visceral metastases, PSA >100ng/ml, ISUP4+5 and later administration of Docetaxel were predictors of OM.ConclusionReal-world experiences indicate that favorable oncologic outcomes can be achieved with CAB especially regarding PSA-response and OS even in the fourth line or later in patients with mCRPC.     

PSA nadir and time to PSA nadir during initial androgen deprivation therapy as prognostic factors in metastatic castration-resistance prostate cancer patients treated with docetaxel

Prostate-specific antigen nadir (nPSA) and time to nPSA (TTN) have been proved to be associated with the prognosis of prostate cancer. In this study, we explored the prognosis effect of nPSA and TTN during initial androgen deprivation therapy (ADT) in patients with metastatic castration-resistant prostate cancer (mCRPC) after treatment with docetaxel-based chemotherapy. The data of 153 mCRPC patients received docetaxel followed by ADT were retrospectively reviewed. Multivariate Cox regression analysis demonstrated that TTN (overall survival (OS): Hazard ratio [HR] 0.096, 95% confidence interval [CI] 0.045–0.206, p < .001; progression-free survival (PFS): HR 0.128, 95% CI 0.078–0.211, p < .001) and nPSA (OS: HR 2.849, 95% CI 1.318–6.157, p = .008; PFS: HR 1.573, 95% CI 1.008–2.454, p = .046) acted as independent predictors of chemotherapy prognosis. Kaplan-Meier analysis showed that patients with nPSA ≥ 0.2 ng/ml or TTN < 6.5 months had shorter OS and PFS. These results suggest that TTN and nPSA during ADT can affect the prognosis of docetaxel-based chemotherapy prognosis post-castration resistance in patients with mCRPC, and higher nPSA and shorter TTN lead to poor chemotherapy prognosis. What is more, TTN has a greater impact during ADT on the prognosis of chemotherapy than nPSA.     

Oncological outcome of docetaxel-based chemotherapy for Japanese men with metastatic castration-resistant prostate cancer

ObjectivesTo retrospectively review the oncologic outcomes of docetaxel-based chemotherapy in Japanese men with metastatic castration-resistant prostate cancer (mCRPC).Materials and methodsThis study included 257 consecutive Japanese patients with mCRPC who were treated with docetaxel-based chemotherapy between April 2007 and March 2010. The prognostic significance of several clinicopathologic factors in these patients was analyzed.ResultsIn these 257 patients, the median age and serum value of prostate-specific antigen (PSA) prior to docetaxel-based chemotherapy were 72 years and 43.0 ng/ml, respectively. Of these patients, 64 (24.9%) and 193 (75.1%) received docetaxel as a weekly (30 mg/m²) and 3-weekly (70–75 mg/m²) regimen, respectively, and estramustine (EM) was administered in combination with docetaxel in 137 (53.3%). PSA decline was observed in 205 patients (79.8%), including 143 (55.6%) achieving PSA decline ≥ 50%. The median progression-free survival and overall survival (OS) were 4.3 and 25.4 months, respectively. Of several factors examined, univariate analysis identified performance status (PS), PSA value, significant clinical pain, bone metastasis, prior treatment with EM, treatment cycle, and PSA response as significant predictors of OS, of which only PS, significant clinical pain, prior treatment with EM, treatment cycle, and PSA response appeared to be independently related to OS on multivariate analysis. Furthermore, there were significant differences in OS according to positive numbers of these 5 independent risk factors.ConclusionsOncologic outcomes in Japanese mCRPC patients receiving docetaxel-based chemotherapy is generally favorable, and the risk stratification presented in this study may contribute to precisely predicting the prognosis of such patients.     

Docetaxel reintroduction in patients with metastatic castration‐resistant docetaxel‐sensitive prostate cancer: a retrospective multicentre study

OBJECTIVE

To investigate the potential benefit of reintroducing docetaxel chemotherapy in patients with progressive metastatic castration‐resistant prostate cancer (mCRPC) who had initially responded to first‐line docetaxel‐based regimen.

PATIENTS AND METHODS

Records were evaluated retrospectively from French patients with mCRPC who had been included in seven controlled clinical studies of docetaxel as first‐line treatment. We identified patients who were confirmed as responders to first‐line treatment, discontinued for reasons other than disease progression or unacceptable toxicity, and who received further docetaxel chemotherapy for disease progression. The primary objective was to assess efficacy in terms of the prostate‐specific antigen (PSA) response after resuming a docetaxel‐based chemotherapy. Secondary objectives were overall survival and tolerance.

RESULTS

Of the 148 patients who responded to first‐line docetaxel, 50 received further therapy with docetaxel and were analysed. The median (range) response duration to first‐line docetaxel was 10.3 (4.6–45.7) months and the median docetaxel‐free interval was 18.4 (5.0–46.7) months. Docetaxel was reintroduced as second‐line therapy in 52% of patients and as further lines in 48%. After docetaxel reintroduction, 24 patients (48%) had a 50% decrease in PSA level (95% confidence interval, CI, 34.1–61.8%). The median (95% CI) overall survival from docetaxel reintroduction was 16 (13–20) months. Re‐treatment was well tolerated (6% of grade 3–4 haemotoxicity).

CONCLUSION

Docetaxel reintroduction appears to be effective, with favourable tolerance profiles, in patients with mCRPC having responded to first‐line docetaxel, and should be prospectively assessed in clinical trials against alternative therapies or investigational agents given alone or in combination, to define further management.     

El índice nutricional pronóstico como factor pronóstico independiente para la respuesta al tratamiento,la supervivencia y la elección del fármaco en el cáncer de próstata metastásico resistente a la castración tratado con acetato de abiraterona o enzalutamida

PurposeWe designed this study to identify the prognostic value of baseline prognostic nutritional index (PNI) in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate or enzalutamide.MethodsOne hundred one mCRPC patients were included. PNI was calculated using formula 10 × serum albumin value (g/dl) + .005 × total lymphocyte count (per mm³). ROC analysis was used for determining prognostic PNI value.ResultsThe statistically significant cut-off value for PNI was 46.62. Initial PSA response and PSA kinetics (early PSA response and 30-50%-90% PSA response at any time) were much better in PNI>46.62 group than the PNI ≤46.62 group (P<.01). In multivariate analysis, baseline PNI level >46.62 was an independent predictor of PSA-PFS (HR: .42; P<.01), radiologic PFS (HR: .53; P<.01), and OS (HR: .42; P<.01). In the PNI≤46.62 group, median OS was 7.4 months (95% CI: 4.1-10.7) for the abiraterone acetate subgroup vs. 17.6 months (95% CI: 10.1-25.1) for enzalutamide subgroups (P<.01).ConclusionPNI is a useful, independent prognostic marker for mCRPC patients treated with either abiraterone acetate or enzalutamide. Using pre-treatment PNI may help clinicians in the prediction of survival and decision making based on abiraterone acetate or enzalutamide.     

Clinical outcomes in a contemporary series of “young” patients with castration-resistant prostate cancer who were 60 years and younger

BackgroundThe prognosis of younger patients with prostate cancer is unclear, and the very few studies assessing those with metastatic castration-resistant prostate cancer (mCRPC) have mainly involved patients treated with older therapies. The aim of this observational study was to evaluate the clinical outcomes of a contemporary series of docetaxel-treated patients with mCRPC who were 60 years and younger.Patients and methodsWe retrospectively identified 134 patients who were 60 years and younger who were treated with docetaxel in 25 Italian hospitals and recorded their predocetaxel history of prostate cancer, their characteristics at the start of chemotherapy, and their postdocetaxel treatment history and outcomes.ResultsMost of the 134 consecutive patients with mCRPC received the standard 3-week docetaxel schedule; median progression-free survival (PFS) was 7 months, and 90 patients underwent further therapies after progression. The median overall survival (OS) from the start of docetaxel treatment was 21 months, but OS was significantly prolonged by the postprogression treatments, particularly those based on the new agents such as cabazitaxel, abiraterone acetate, or enzalutamide. OS was significantly shorter in the patients with a shorter interval between the diagnosis of prostate cancer and the start of docetaxel treatment; those who received hormonal treatment for a shorter period; those with shorter prostate-specific antigen doubling times; and those with lower hemoglobin levels, a worse performance status, and higher lactate dehydrogenase levels before starting treatment with docetaxel.ConclusionsThe findings of this first study of clinical outcomes in a contemporary series of younger patients with mCRPC showed that their survival is similar to that expected in unselected patients with mCRPC who were of any age.     

Significance of docetaxel-based chemotherapy as treatment for metastatic castration-resistant prostate cancer in Japanese men over 75?years old

Objectives

The objective of this study was to evaluate the significance of docetaxel-based chemotherapy in elderly Japanese men with metastatic castration-resistant prostate cancer (CRPC).

Materials and methods

This study included a total of 159 consecutive patients aged ??75?years with mCRPC who were treated with docetaxel-based chemotherapy. The efficacy and tolerability of this therapy were retrospectively analyzed.

Results

In these 159 patients, the median age and prostate-specific antigen (PSA) level before docetaxel-based chemotherapy were 78?years and 44.0?ng/ml, respectively. Of these patients, 42 (26.4?%) and 117 (73.6?%) received docetaxel as a weekly (30?mg/m²) and 3-weekly (70?mg/m²) regimen, respectively, and estramustine was administered combining with docetaxel in 77 (48.4?%). Following docetaxel-based chemotherapy, PSA declined in 118 patients (74.3?%), including 87 (54.6?%) achieving a PSA decline ??50?%, and the median progression-free survival and overall survival (OS) were 2.9 and 23.2?months, respectively. Of several factors examined, univariate analysis identified performance status (PS), significant clinical pain, bone metastasis, schedule of treatment, treatment cycle, and PSA response as significant predictors of OS, of which only PS, treatment cycle, and PSA response appeared to be independently associated with OS on multivariate analysis. The major grade 3?C4 toxicities were myelosuppression, including neutropenia, anemia, and thrombocytopenia in 78 (49.1?%), 22 (13.8?%), and 14 (8.8?%), respectively.

Conclusions

These findings suggest that docetaxel-based chemotherapy is clinically feasible in Japanese men aged ??75?years with mCRPC considering the cancer control as well as safety associated with this therapy.     

Baseline basophil and basophil-to-lymphocyte status is associated with clinical outcomes in metastatic hormone sensitive prostate cancer

BackgroundBiomarkers have the potential to provide clinical guidance, but there is limited data for biomarkers in metastatic hormone sensitive prostate cancer (mHSPC).MethodsWe performed a retrospective multicenter review from Winship Cancer Institute at Emory University and Georgia Cancer Center for Excellence at Grady Memorial Hospital (2014–2020) in the United States of America (USA). We collected demographics, disease characteristics, and laboratory data, including complete blood counts (CBC) at the start of upfront therapy. We evaluated overall survival (OS) and progression-free survival (PFS) associated with baseline lab values.Results165 patients were included with a median follow-up time of 33.5 months (mo). 105 (63.6%) had Gleason scores of 8-10 and 108 (65.9%) were classified as high-volume disease. 92 patients received upfront docetaxel (55.8%) and 73 received upfront abiraterone (44.2%). Univariate analyses (UVA) and multivariable analyses (MVA) identified worse clinical outcomes (CO) associated with elevated basophils and basophil-to-lymphocyte ratio (BLR). Based on MVA, elevated basophils (defined as ≥0.1, optimal cut) were associated with a hazard ratio (HR) of 3.51 (95% CI 1.65–7.43, P 0.001) for OS and HR of 1.88 (95% CI 1.05-3.38, P 0.034) for PFS. Our MVA also found that BLR ≥0.0142 was associated with HR 2.11 (95% CI 1.09–4.10, P 0.028) for OS; however, PFS was not statistically significant.ConclusionWe conclude that elevated baseline basophils and BLR are associated with worse clinical outcomes in mHSPC. Although results require further validation, BLR is a potential prognostic biomarker.     

Prostate-specific antigen half-life： a new predictor of progression- free survival and overall survival in Chinese prostate cancer patients

We investigated the potential value of prostate-specific antigen half-life （PSAHL） and decreasing velocity （PSAVd） to predict progression-free survival （PFS） and overall survival （OS） in Chinese patients with prostate cancer. A total of 153 patients treated with hormonal therapy were included in the study. Of these, 78 patients progressed to hormone- refractory prostate cancer （HRPC） and 24 patients died by the end of follow-up. PSAHL was defined as the time during which prostate-specific antigen （PSA） concentration became half of the initial value during the first hormonal therapy. PSAVd reflected the decreasing velocity of PSA during the first hormonal therapy. PFS was defined as the interval from the beginning of hormonal therapy to HRPC. Cox proportional hazards regression analysis was used to evaluate whether PSAHL and PSAVd were significantly associated with PFS and OS. The median PSAHL and PSAVd were 0.50 months and 33.8 ng mL^-1 per month. The median PFS and OS were 22.7 months （95% confidence interval [CI], 22.0-29.6 months） and 43.5 months （95% CI, 37.9-48.4 months）, respectively. On univariate and multivariate analysis, long PSAHL （〉 0.5 months）, metastatic disease, high biopsy Gleason scores （〉 8） and high nadir PSA （〉 0.4 ng mL^-1） were all found to be significantly associated with short PFS. Long PSAHL, high nadir PSA and short PSA doubling time （PSADT 〈 2.0 months） were significantly associated with short OS. There were no significant relationships between PSAVd and either PFS or OS. Thus, PSAHL is a promising new independent predictor of survival. Patients with long PSAHL were identified as those at high risk for a relatively short PFS and OS.     

Trastuzumab,Pertuzumab, and Docetaxel as the First Line for HER-2-Positive Metastatic Breast Cancer among Arabs

IntroductionHuman epidermal growth factor receptor 2 (HER-2) targeted therapy regimens can improve tumor response in HER-2-positive metastatic breast cancer (MBC), with overall survival benefits.ObjectiveWe evaluated the efficacy of dual HER-2 blockade combined with chemotherapy for HER-2-positive MBC patients as a first-line therapy in our patient population.Patients and MethodsWe identified 75 patients at King Faisal Specialist Hospital and Research Center that received trastuzumab, pertuzumab, and docetaxel as a first-line therapy in HER-2 positive MBC in 2013–2016.ResultsMedian age at diagnosis was 45 years; 54.7% were estrogen receptor (ER)-positive. 10% of patients presented with only bone metastasis. The median follow-up time was 36 months with an objective response rate of 74.7% (complete response [CR] 18.7%; partial response [PR] 56%). The 5-year progression-free survival (PFS) and overall survival (OS) were 21% and 71.9% respectively, with a median PFS of 36 months (95% confidence interval [CI] 23.6–48.4). The 5-year OS for ER-negative and ER-positive patients was 93.9% and 59.4% respectively (p = 0.189); 23 patients experienced grade 1/2 toxicity and 2 patients had grade 3/4 toxicity. In terms of OS and PFS, the site of metastasis did not make any significant difference.ConclusionsFirst line pertuzumab, trastuzumab, and docetaxel for HER-2-positive MBC patients was found to be an effective and safe therapy in the Saudi population. This finding was consistent with the results seen in the CLEOPATRA trials.     

Activity and Adverse Events of Actinium-225-PSMA-617 in Advanced Metastatic Castration-resistant Prostate Cancer After Failure of Lutetium-177-PSMA

BackgroundBeta-emitting Lu-177-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a new option for metastatic castration-resistant prostate cancer (mCRPC), but its antitumor effect can decrease over time.ObjectiveTo report the safety and activity of alpha-emitting Ac-225-PSMA-617 RLT in mCRPC that has progressed after Lu-177-PSMA.Design, setting, and participantsTwenty-six patients were treated under a compassionate use protocol. The eligibility criteria included previous treatment with abiraterone or enzalutamide, previous taxane-based chemotherapy, progression after Lu-177-PSMA, and positive PSMA-ligand uptake. The median number of previous mCRPC regimens was 6. Ac-225-PSMA-617 was given every 8 wk until progression/intolerable side effects.Outcome measurements and statistical analysisProstate-specific antigen (PSA) decline, PSA progression-free survival (PSA-PFS), clinical progression-free survival (cPFS), overall survival (OS), and toxicity were measured.Results and limitationsSixty-one cycles of Ac-225-PSMA-617 (median number of cycles 2; median activity 9 MBq) were administered. A PSA decline of ≥50% was achieved in 17/26 patients. The median PSA-PFS, cPFS, and OS periods were 3.5 (95% confidence interval [CI] 1.8–11.2), 4.1 (95% CI 3–14.8), and 7.7 (95% CI 4.5–12.1) mo, respectively. Liver metastases were associated with shorter PSA-PFS (median 1.9 vs 4.0 mo; p = 0.02), cPFS (median 1.8 vs 5.2 mo; p = 0.001), and OS (median 4.3 vs 10.4 mo; p = 0.01). Hematological grade 3/4 toxicities were anemia (35%), leucopenia (27%), and thrombocytopenia (19%). All patients experienced grade 1/2 xerostomia. Two and six patients stopped due to hematological toxicity and xerostomia, respectively. A limitation is the retrospective design.ConclusionsAc-225-PSMA-617 showed measurable antitumor effect after Lu-177-PSMA failure in late-stage mCRPC. Grade 3/4 hematological side effects were observed in up to one-third of patients, and xerostomia led to treatment halt in a relevant number of patients.Patient summaryAc-225-labeled prostate-specific membrane antigen (PSMA)-617 therapy showed substantial antitumor effect in late metastatic castration-resistant prostate cancer after Lu-177-PSMA failure. However, dry mouth is a common side effect that caused about a quarter of patients to stop therapy.     

Efficacy and safety of bipolar androgen therapy in mCRPC after progression on abiraterone or enzalutamide: A systematic review

PurposeTo further determine the efficacy and safety of bipolar androgen therapy (BAT) on patients with metastatic castration-resistant prostate cancer (mCRPC) after progression on abiraterone (ABI) or enzalutamide (ENZA).Materials and methodsWe systematically searched the Pubmed, Web of Science and ClinicalTrials.gov up to June 2021. Literature review, study selection, and data extraction were conducted by 2 reviewers. Risk of bias was assessed according to the methodology of the European Association of Urology (EAU). A systematic review and pooled analysis were performed. The primary outcomes were PSA50 after BAT and AR-targeted therapy rechallenge, objective response rate (ORR) after BAT, and AEs after BAT. The definition of PSA50 was that participants achieving a PSA decline ≥50% according to Prostate Cancer Working Group (PCWG2) criteria. The ORR determined by determined by Response Evaluation Criteria in Solid Tumors (RECIST) included patients experienced partial response (PR) or complete response (CR).ResultsIn a total of 74 unique records, 5 studies were eligible for inclusion. Participants who underwent BAT achieved PSA50 of 0.26 (95% CI [0.20, 0.32]) and objective response rate (ORR) of 0.32 (95% CI [0.21, 0.44]). Patients completed BAT proceeded to AR-target therapy (ABI or ENZA) achieved moderate response (PSA50 0.54, 95% CI [0.30, 0.76]). Based on our multiple subgroup analysis, type of post-BAT AR-target therapy had a strong impact on PSA50 of AR-target therapy rechallenge. Most of adverse events (AEs) were low grade.ConclusionsThe present study indicated that BAT could induce clinical responses in mCRPC patients after progression on ABI or ENZA, with an acceptable side effects profile. BAT could also be able to restore sensitivity to ABI and ENZA rechallenge in a subset of patients.     

阿比特龙联合泼尼松治疗老年转移性去势抵抗前列腺癌的临床观察

［摘要］ 目的 观察分析阿比特龙联合泼尼松治疗老年未经化疗转移去势抵抗前列腺癌（mCRPC）患者的效果及安全性。方法 2017年01月至2019年1月广州市第一人民医院收治36例未化疗老年转移性去势抵抗前列腺癌（mCRPC）患者，给予醋酸阿比特龙1000 mg，每日1次空腹口服，强的松片5 mg，每日2次口服。观察患者血清前列腺特异抗原（PSA）缓解率及毒副反应等。结果 36例患者中位随访15.8个月，23例mCRPC患者（63.9%）达到PSA缓解，TPSA≤100 ng/mL的缓解率64.7%，TPSA>100 ng/mL的缓解率63.2%；Gleason评分<8的缓解率42.8%，=8的缓解率为63.6%，>8的缓解率为90.9%；骨转移≤10的缓解率为54.5%，>10的缓解率为60%。23例mCRPC达PSA缓解患者中，8例出现PSA Flare，15例未出现PSA Flare。36例mCRPC患者中10例出现PSA Flare现象，有7例达到PSA缓解，26例未出现PSA Flare的mCRPC患者中，有15例达到PSA缓解。不良反应为肝功损害、低血钾、水钠潴留、高血压。未发现导致无法继续治疗的严重不良反应。结论 阿比特龙联合泼尼松治疗未化疗的老年mCRPC患者疗效肯定，副作用小，安全性好，除Gleason评分外，不同基线值与患者预期疗效无关联，PSA Flare现象一定程度上使肿瘤对药物反应更积极。     

KDM5D predicts response to docetaxel chemotherapy in metastatic castration resistant prostate cancer patients

BackgroundThe administration of docetaxel chemotherapy is one therapeutic option to delay disease progression and increase overall survival in metastatic castration resistant prostate cancer (mCRPC). However, about 15% of patients are primary resistant to chemotherapy and hence would benefit from an alternative mCRPC treatment. Despite intensive research, there are no robust clinical validated biomarkers to predict mCRPC therapy response. Thus, the aim of the study was to determine KDM5D expression in archival radical prostatectomy specimens of patients medicated with docetaxel at time of mCRPC development in order to correlate KMD5D expression with treatment response.MethodsWe used in situ hybridization (ISH) (RNA scope 2.5 HD) to determine KDM5D expression in tissue samples of 28 prostate cancer patients. KDM5D status was correlated to chemotherapy response (PSA and radiographic response).ResultsData revealed that KDM5D is significantly overexpressed in tumor cells (P<0.0001) but also in benign cells (P<0.02) of those patients who responded to chemotherapy compared to non-responders.ConclusionsTo summarize, KDM5D is a promising novel biomarker predicting response to docetaxel chemotherapy already at the time of localized disease and thus potentially avoiding metastatic biopsies in the mCRPC stage of disease.     

Anticancer Activity and Tolerance of Treatments Received Beyond Progression in Men Treated Upfront with Androgen Deprivation Therapy With or Without Docetaxel for Metastatic Castration-naïve Prostate Cancer in the GETUG-AFU 15 Phase 3 Trial

Background

Androgen deprivation therapy (ADT) plus docetaxel is the standard of care in fit men with metastatic castration-naive prostate cancer (mCNPC) following results from GETUG-AFU 15, CHAARTED, and STAMPEDE. No data are available on the efficacy of treatments used for metastatic castration-resistant prostate cancer (mCRPC) in men treated upfront with ADT plus docetaxel for mCNPC.