The impact of patient characteristics on enzalutamide pharmacokinetics and how this relates to treatment toxicity and efficacy in metastatic prostate cancer patients

171 Background: The risk of prostate cancer (PCa)-death in men diagnosed with metastatic (M+) PCa is high. During the past decade, new life-prolonging therapies have been approved for the treatment of advanced PCa. Even though demonstrated in randomized clinical trials, the impact of these advancements on mortality of men with newly diagnosed M+ PCa has not been described in a nation-wide setting. Methods: In the Danish Prostate Cancer Registry (DaPCaR), all men diagnosed with M+ PCa in Denmark from 1995 to 2011 were identified. Patients were grouped according to the year of diagnosis; 1995-2000, 2001-2005 and 2006-2011. In a competing risk setting, the 5-year cumulative incidences of PCa, other-cause, and overall death were calculated. Multivariate cause-specific Cox analysis was performed. Results: A total of 1,892 (1995-2000), 2,329 (2001-2005), and 2,653 (2006-2011) men were included (total: 6,874). Patient characteristics at diagnosis showed essential differences as median age and median PSA decreased by 1.0 year (74.1 to 73.1) and 134 ng/mL (276 to 142), respectively, in the period studied. The 5-year PCa-specific mortality decreased by 17.0% from 72.8% (1995-2000) (95%CI: 70.8% – 74.8%) to 55.8% (2006-2011) (95%CI: 53.9% – 57.7%), p < 0.0001. The 5-year other-cause mortality increased by 5.7% from 11.4% (95%CI: 9.9% – 12.8%) to 17.1% (95%CI: 15.6 – 18.6), p < 0.0001. The risk of PCa-death decreased for patients diagnosed in 2000-2005; HR: 0.69 (95%CI 0.61-0.79) and for patients diagnosed in 2006-2011; HR: 0.53 (95%CI 0.47-0.61) compared to patients diagnosed in 1995-2000, when adjusting for age, PSA, and Gleason score (GS) in the statistical analysis. Conclusions: A significant reduction in 5-year PCa-specific mortality was observed in a nationwide cohort of patients diagnosed with M+ PCa since 1995. Changes in age and PSA at diagnosis suggest that lead-time introduced by increased PSA use may have affected the results. However, in multivariate analysis, a significant reduction in hazard of almost 50% was observed when adjusting for age, PSA, and GS. Only minor changes in other cause mortality were found, which suggests that the improvement to a large extend can be credited to improved management of men with advanced PCa.

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The impact of time to metastasis on survival in treatment-naïve prostate cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.212 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 212-212

Author(s):

Shusuke Akamatsu ◽

Kenny Lynch ◽

Peter Black ◽

Martin Gleave ◽

Larry Goldenberg ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Median Time ◽

De Novo ◽

Patient Characteristics ◽

Initial Diagnosis ◽

Significant Difference ◽

Treatment Naïve ◽

The Impact

212 Background: With the emergence of novel therapies, the treatment of advanced prostate cancer has evolved. However, patients eventually succumb to their metastatic disease. Nonetheless, little is known about the impact of time to metastasis on survival. To further expand on this, we separated metastatic prostate cancer patients into three groups according to the timing of metastasis and analyzed their survival. Methods: From 2008 to 2013, 157 CRPC patients were identified in our database. Of those, 92 with metastasis and sufficient data were analysed. The patients were classified into three groups according to the timing of metastasis. There were 35 de novo –M (metastasis within three months of initial diagnosis), 26 CSPC-M (initially metastasis free, metastasis found more than 6 months prior to CRPC), and 31 CRPC-M (metastasis found within 6 months of becoming CRPC, or after becoming CRPC). Patient characteristics were analyzed, and survival was calculated. Results: Median follow up were 2.2, 9.6, and 11.8 years for de novo-M, CSPC-M, and CRPC-M. 85 and 84 % in the CSPC-M and CRPC-M respectively had local therapies by surgery and/or radiation. The types of local therapies were similar between the groups. Mean time to PSA recurrence after intial therapy were 3.5 and 2.2 years for CSPC-M and CRPC-M, and median time to metastasis were 4.4 and 11.4 years respectively. Treatments after CRPC included Abiraterone, Enzalutamide, and Docetaxel, and the use of these agents were similar between the groups. Median time to CRPC were 1.4, 6.2, and 8.6 years, and median overall survival after diagnosis were 3.7, 12.3, and 15.8 years for de novo-M, CSPC-M, and CRPC-M. Conclusions: The overall survival and time to CRPC were significantly shorter in de novo-M. Although there was a marked difference in time to metastasis between CSPC-M and CRPC-M, there was no statistically significant difference in overall survival. Either treated with hormone therapy before or after emergence of metastasis, survival of more than 10 years after initial diagnosis is possible.

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158: The Impact of Skeletal-Related Events on Preferences and Health-Related Quality of Life of Patients with Metastatic Prostate Cancer

The Journal of Urology ◽

10.1016/s0022-5347(18)37420-2 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 42-42 ◽

Cited By ~ 1

Author(s):

Kevin P. Weinfurt ◽

Liana D. Castel ◽

Yun Li ◽

Fred Saad ◽

Justin W. Timbie ◽

...

Keyword(s):

Quality Of Life ◽

Prostate Cancer ◽

Metastatic Prostate Cancer ◽

Health Related Quality ◽

Related Quality ◽

Health Related ◽

Skeletal Related Events ◽

The Impact

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Resistance Training +/- Creatine for Metastatic Prostate Cancer Patients

Case Medical Research ◽

10.31525/ct1-nct03987217 ◽

2019 ◽

Author(s):

Keyword(s):

Prostate Cancer ◽

Resistance Training ◽

Cancer Patients ◽

Metastatic Prostate Cancer

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Prognostic role of docetaxel-induced suppression of free testosterone serum levels in metastatic prostate cancer patients

Scientific Reports ◽

10.1038/s41598-021-95874-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Paula Kappler ◽

Michael A. Morgan ◽

Philipp Ivanyi ◽

Stefan J. Brunotte ◽

Arnold Ganser ◽

...

Keyword(s):

Prostate Cancer ◽

Metastatic Prostate Cancer ◽

Cox Regression ◽

Specific Antigen ◽

Progression Free Survival ◽

Serum Levels ◽

Biologically Active ◽

Free Form ◽

Total Testosterone ◽

The Impact

AbstractTo date, only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer (mPC) and the impact of FT on disease, therapy and outcome is largely unknown. We retrospectively studied the effect of docetaxel on FT and total testosterone (TT) serum levels in 67 mPC patients monitored between April 2008 and November 2020. FT and TT levels were measured before and weekly during therapy. The primary endpoint was overall survival (OS). Secondary endpoints were prostate-specific antigen response and radiographic response (PSAR, RR), progression-free survival (PFS), FT/TT levels and safety. Median FT and TT serum levels were completely suppressed to below the detection limit during docetaxel treatment (FT: from 0.32 to < 0.18 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified requirement of non-narcotics, PSAR, complete FT suppression and FT nadir values < 0.18 pg/mL as independent parameters for PFS. Prior androgen-receptor targeted therapy (ART), soft tissue metastasis and complete FT suppression were independent prognostic factors for OS. FT was not predictive for treatment outcome in mPC patients with a history of ART.

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