Population Pharmacokinetic Analysis of Abiraterone in Chemotherapy-Naïve and Docetaxel-Treated Patients with Metastatic Castration-Resistant Prostate Cancer

Stuyckens, Kim; Saad, Fred; Xu, Xu Steven; Ryan, Charles J.; Smith, Matthew R.; Griffin, Thomas W.; Yu, Margaret K.; Vermeulen, An; Nandy, Partha; Poggesi, Italo

doi:10.1007/s40262-014-0178-6

Cited by 48 publications

(32 citation statements)

References 29 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The shrinkage was small (\10 %) for the primary pharmacokinetic parameter (i.e. apparent oral clearance) and has been previously reported [11].…”

Section: Modeling Drug Effect On the Pharmacodynamics Of Psasupporting

confidence: 68%

“…Post-treatment PSA measurements were obtained after at least 4 weeks of exposure to abiraterone; individual steadystate trough concentrations (C min ) were used to drive the pharmacokinetics-PSA dynamics. The individual steadystate C min were predicted based on the individual parameters derived from a two-compartment pharmacokinetic model [11].…”

Section: Assessment Of Exposure To Abirateronementioning

confidence: 99%

“…prednisone) versus prednisone alone; and (ii) by individual to evaluate the exposure-response relationship using individual predicted concentration data (e.g. C min ) based on a population pharmacokinetic model for abiraterone [11]. The treatment effect h TRT (abiraterone acetate ?…”

Section: Modeling Drug Effect On the Pharmacodynamics Of Psamentioning

confidence: 99%

“…The individual steady-state C min (empirical Bayes estimates) for the pharmacokinetic population was predicted using the published population pharmacokinetic model [11], while the C min was set to 0 for patients from the prednisone arm, since prednisone coadministered with abiraterone acetate is an active agent and this arm provided important baseline data. It should be noted that steady-state AUC was also tested to fit the model.…”

Section: Modeling Drug Effect On the Pharmacodynamics Of Psamentioning

confidence: 99%

See 3 more Smart Citations

Modeling the Relationship Between Exposure to Abiraterone and Prostate-Specific Antigen Dynamics in Patients with Metastatic Castration-Resistant Prostate Cancer

Ryan

Stuyckens

et al. 2016

Clin Pharmacokinet

Self Cite

View full text Add to dashboard Cite

show abstract

“…The shrinkage was small (\10 %) for the primary pharmacokinetic parameter (i.e. apparent oral clearance) and has been previously reported [11].…”

Section: Modeling Drug Effect On the Pharmacodynamics Of Psasupporting

confidence: 68%

Section: Assessment Of Exposure To Abirateronementioning

confidence: 99%

Section: Modeling Drug Effect On the Pharmacodynamics Of Psamentioning

confidence: 99%

Section: Modeling Drug Effect On the Pharmacodynamics Of Psamentioning

confidence: 99%

See 2 more Smart Citations

Modeling the Relationship Between Exposure to Abiraterone and Prostate-Specific Antigen Dynamics in Patients with Metastatic Castration-Resistant Prostate Cancer

Ryan

Stuyckens

et al. 2016

Clin Pharmacokinet

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although initially responsive to androgen deprivation therapy (ADT), nearly all metastatic PCa progress to a castrate-resistant prostate cancer (CRPC) phase with poor prognosis [2]. Although some CRPCs respond to chemotherapeutic drugs, like docetaxel [3] or cabazitaxel [4], the benefit is limited and often short-lived. Recent studies have cemented earlier observations that deregulation of androgen-receptor (AR) signaling and the PI3K/AKT/mTOR pathways play important roles in carcinogenesis, progression and development of resistance [5–7].…”

Section: Introductionmentioning

confidence: 99%

Combination effect of therapies targeting the PI3K- and AR-signaling pathways in prostate cancer

Yadav

Stockert

et al. 2016

Oncotarget

View full text Add to dashboard Cite

Several promising targeted-therapeutics for prostate cancer (PCa), primarily affecting the androgen receptor (AR) and the PI3K/AKT/mTOR-pathway, are in various phases of development. However, despite promise, single-agent inhibitors targeting the two pathways have not shown long-term benefits, perhaps due to a complex compensatory cross talk that exists between the two pathways. Combination therapy has thus been proposed to maximize benefit. We have carried out a systematic study of two-drug combination effect of MDV3100 (AR antagonist), BKM120 (PI3K inhibitor), TKI258 (pan RTK inhibitor) and RAD001 (mTOR inhibitor) using various PCa cell lines. We observed strong synergy when AR-positive cells are treated with MDV3100 in combination with any one of the PI3K-pathway inhibitors: TKI258, BKM120, or RAD001. Growth curve based synergy determination combined with Western blot analysis suggested MDV3100+BKM120 to be the most effective in inducing cell death in such conditions. In the case of dual targeting of the PI3K-pathway BKM120+TKI258 combination displayed exquisite sensitivity in all the 5 cell lines tested irrespective of androgen sensitivity, (LNCaP, VCaP, 22Rv1, PC3 and Du145). The effect of blockade with BKM120+TKI258 in PC3 cells was similar to a combination of BKM120 with chemotherapy drug cabazitaxel.Taken together, our observation supports earlier observations that a combination of AR-inhibitor and PI3K-inhibitor is highly synergistic. Furthermore, combining BKM120 with TKI258 has better synergy than BKM120+RAD001 or RAD001+TKI258 in all the lines, irrespective of androgen sensitivity. Finally, BKM120 also displayed synergy when combined with chemotherapy drug cabazitaxel. No antagonism however was observed with any of the drug combinations.

show abstract

Liquid biopsy reveals KLK3 mRNA as a prognostic marker for progression free survival in patients with metastatic castration‐resistant prostate cancer undergoing first‐line abiraterone acetate and prednisone treatment

Boerrigter¹,

Benoist²,

Oort

et al. 2021

Molecular Oncology

View full text Add to dashboard Cite

Circulating RNAs extracted from liquid biopsies represent a promising source of cancer and therapy-related biomarkers. We screened whole blood from patients with metastatic castration-resistant prostate cancer (mCRPC) following their first-line treatment with abiraterone acetate and prednisone (AA-P) to identify circulating RNAs that may correlate with progression free survival (PFS).In a prospective multi-center observational study, 53 patients with mCRPC were included after they started first-line AA-P treatment. Blood was drawn at baseline, one, three and six months after treatment initiation.The levels of pre-defined circulating RNAs earlier identified as being upregulated in patients with mCRPC (e.g. microRNAs, long non-coding RNAs and messenger RNAs), were analyzed. Uni-and multi-variable Cox regression and Kaplan-Meier analyses were used to analyze the prognostic value of the various circulating RNAs for PFS along treatment.Detectable levels of KLK3 mRNA at baseline were demonstrated to be an independent prognostic marker for PFS (201 vs 501 days, P=0.00054). Three months after AA-P treatment initiation, KLK3 could not be detected in the blood of responding patients, but was still detectable in 56% of the patients with early progression.Our study confirmed that KLK3 mRNA detection in whole blood is an independent prognostic marker in mCRPC patients receiving AA-P treatment. Furthermore, the levels of circulating KLK3 mRNA in patients receiving AA-P treatment might reflect treatment response or early signs of progression.

show abstract

Population Pharmacokinetic Analysis of Abiraterone in Chemotherapy-Naïve and Docetaxel-Treated Patients with Metastatic Castration-Resistant Prostate Cancer

Cited by 48 publications

References 29 publications

Modeling the Relationship Between Exposure to Abiraterone and Prostate-Specific Antigen Dynamics in Patients with Metastatic Castration-Resistant Prostate Cancer

Modeling the Relationship Between Exposure to Abiraterone and Prostate-Specific Antigen Dynamics in Patients with Metastatic Castration-Resistant Prostate Cancer

Combination effect of therapies targeting the PI3K- and AR-signaling pathways in prostate cancer

Liquid biopsy reveals KLK3 mRNA as a prognostic marker for progression free survival in patients with metastatic castration‐resistant prostate cancer undergoing first‐line abiraterone acetate and prednisone treatment

Contact Info

Product

Resources

About