An exploratory retrospective multicenter study of prognostic factors in mCRPC patients undergoing enzalutamide treatment: Focus on early PSA decline and kinetics at time of progression

Miyazawa, Yoshiyuki; Sekine, Yoshitaka; Shimizu, Nobuaki; Takezawa, Yutaka; Nakamura, Toshiyuki; Miyao, Takeshi; Nakayama, Hiroshi; Kurihara, Shuichi; Syuto, Takahiro; Nomura, Masashi; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Suzuki, Kazuhiro

doi:10.1002/pros.23865

Cited by 22 publications

(12 citation statements)

References 27 publications

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“…In this study, the multivariate analysis revealed that the time to CRPC within 12 months was the independent predictive factor for poorer PSA-PFS. This finding was consistent with those of previous reports [5,18,19].…”

Section: Plos Onesupporting

confidence: 94%

Initial dose reduction of enzalutamide does not decrease the incidence of adverse events in castration-resistant prostate cancer

et al. 2021

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Background There was no clear evidence whether the initial dose of enzalutamide affects the incidence of adverse events (AEs), and oncological outcome in patients with castration-resistant prostate cancer (CRPC). Methods The clinical charts of 233 patients with CRPC treated with enzalutamide were reviewed retrospectively. After 1:3 propensity score matching (PSM), 124 patients were divided into a reduced dose group and a standard dose group, and the prostate specific antigen (PSA) response and the incidence of AEs were compared. Results 190 patients with CRPC initiated with standard dose enzalutamide were younger and better performance status compared with 43 patients beginning with reduced dose. After PSM, the baseline characteristics were not different between the standard and the reduced dose group. In the PSM cohort, the PSA response rate was significantly lower in the reduced dose group than in the standard dose group (-66.3% and -87.4%, p = 0.02). The incidence rates of AEs were not statistically different between the groups (22.6% and 34.4%, respectively, p = 0.24). Conclusion Initiating treatment with a reduced dose of enzalutamide did not significantly decrease the incidence rate of AEs, and it showed poorer PSA response rate. There is no clear rationale for treating with a reduced initial dose of enzalutamide to reduce the incidence of AEs.

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Section: Plos Onesupporting

confidence: 94%

Initial dose reduction of enzalutamide does not decrease the incidence of adverse events in castration-resistant prostate cancer

et al. 2021

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“…In this study, the multivariate analysis revealed that the time to CRPC within 12months was the independent predictive factor for worse PSA PFS, and lower PSA response to enzalutamide treatment was an independent predictive factor for worse OS. These ndings were consistent with those of previous reports (5,16,17), and suggested that enzalutamide might show strong effects if it was administrated at the early phase of CRPC treatment.…”

Section: Discussionsupporting

confidence: 93%

Reduction of Initial Dose of Enzalutamide does not Decrease the Incidence and Severity of Adverse Events in Castration-Resistant Prostate Cancer

Tsuzuki¹,

Nakanishi²,

Tamaki³

et al. 2020

Preprint

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Background: There was no clear evidence whether the initial dose of enzalutamide affects the incidence of adverse events (AEs), and oncological outcome in patients with castration-resistant prostate cancer (CRPC). Methods: The clinical chart of 233 CRPC patients treated with enzalutamide was reviewed retrospectively. After 1:3 propensity score matching (PSM), 124 patients were classified to whom introduced with full dose of enzalutamide or whom with reduced dose and the oncological outcomes were compared. To investigate the independent predictive factors with progression-free survival (PFS) and overall survival (OS), univariate and multivariate Cox regression analyses were performed.Results: Of total, 190 CRPC patients initiated with full dose enzalutamide were younger and better performance status compared with 43 patients beginning with reduced dose. After PSM, the baseline characteristics were not different between full and reduced dose group. The incidence rate of patients with prostate specific antigen (PSA) decline of >90% in reduced dose group was significantly lower than that in full dose group (34.8% vs46.2%) (p-value 0.03). The incidence rates of AEs were not statistically different between reduced dose group (22.6%) and full dose group (34.4%) (p-value 0.24). On multivariate analyses, initial enzalutamide dose was not a predictive factor of PFS and OS. Conclusion: Initiating with reduced dose of enzalutamide did not significantly decrease the incidence rate of AEs, and it showed less PSA response rate. There is no clear rationale of treating with initial reduction of enzalutamide resulted in overcome incidence of AEs.

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“…Multivariable analysis showed that the plasma level of miR-21 (but not miR-223 or miR-141) was associated with outcome (OS and PFS), independently of other clinical variables. In our evaluation of different clinical parameters usually included in prognostic/predictive models of metastatic prostate cancer (36) time to development of castration resistance and Hb levels were confirmed as independent prognostic factors for OS, findings in line with the results of previous studies of mCRPC patients treated with enzalutamide (37). Interestingly, low Hb levels are also associated with poor survival in several other tumor types (38).…”

Section: Discussionsupporting

confidence: 88%

Prognostic Stratification of Metastatic Prostate Cancer Patients Treated With Abiraterone and Enzalutamide Through an Integrated Analysis of Circulating Free microRNAs and Clinical Parameters

et al. 2021

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Androgen Receptor-Targeted Agents (ARTA) have dramatically changed the therapeutic landscape of metastatic Castration-Resistant Prostate Cancer (mCRPC), but 20–40% of these patients progress early after start of ARTA treatment. The present study investigated the potential utility of plasma cell-free microRNAs (cfmiRNAs) as prognostic markers by analyzing a prospective cohort of 31 mCRCP patients treated with abiraterone (N = 10) or enzalutamide (N = 21). Additional potential prognostic factors were extracted from clinical records and outcome was evaluated as overall survival (OS) and progression-free survival (PFS). cfmiRNAs were measured in plasma samples using quantitative real-time RT-PCR. Linear correlation among clinical factors and cfmiRNAs was assessed using the Spearman's rank correlation coefficient. The association with survival was studied using univariate and multivariate Cox proportional hazards models. Continuous variables were dichotomized with the cut points corresponding to the most significant relation with the outcome. Univariate analysis indicated that plasma levels of miR-21-5p, miR-141-3p and miR-223-3p, time to development of castration-resistance (tCRPC), and blood hemoglobin (Hb) levels strongly correlated with both PFS and OS. Multivariate analysis revealed that low plasma levels of miR-21, shorter tCRPC, and lower Hb values were independent factors predicting reduced PFS and OS. These findings suggest that the integrated analysis of cfmiRNAs, tCRPC, and Hb may provide a promising, non-invasive tool for the prognostic stratification of mCRPC patients treated with ARTA.

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An exploratory retrospective multicenter study of prognostic factors in mCRPC patients undergoing enzalutamide treatment: Focus on early PSA decline and kinetics at time of progression

Cited by 22 publications

References 27 publications

Initial dose reduction of enzalutamide does not decrease the incidence of adverse events in castration-resistant prostate cancer

Initial dose reduction of enzalutamide does not decrease the incidence of adverse events in castration-resistant prostate cancer

Reduction of Initial Dose of Enzalutamide does not Decrease the Incidence and Severity of Adverse Events in Castration-Resistant Prostate Cancer

Prognostic Stratification of Metastatic Prostate Cancer Patients Treated With Abiraterone and Enzalutamide Through an Integrated Analysis of Circulating Free microRNAs and Clinical Parameters

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