- A prospective phase I multicentre randomized cross-over pharmacokinetic study to determine the effect of food on abiraterone pharmacokinetics. [Journal Article]Cancer Chemother Pharmacol 2019CC
- CONCLUSIONS: In conclusion, a bioequivalent lower dose of abiraterone taken with food could not be established in our study. Although based on the absence of a exposure-toxicity relationship, the strict bioequivalence margins as defined by the FDA guidelines could be applied more flexible for abiraterone. Information on the effect of food on abiraterone pharmacokinetics as presented in our study can be used for patients with difficulties taken their medication fasted.
- Detection of Androgen Receptor Variant 7 (ARV7) mRNA Levels in EpCAM-Enriched CTC Fractions for Monitoring Response to Androgen Targeting Therapies in Prostate Cancer. [Journal Article]Cells 2019; 8(9)C
- Expression of the androgen receptor splice variant 7 (ARV7) in circulating tumor cells (CTCs) has been associated with resistance towards novel androgen receptor (AR)-targeting therapies. While a multitude of ARV7 detection approaches have been developed, the simultaneous enumeration of CTCs and assessment of ARV7 status and the integration of validated technologies for CTC enrichment/detection i…
Expression of the androgen receptor splice variant 7 (ARV7) in circulating tumor cells (CTCs) has been associated with resistance towards novel androgen receptor (AR)-targeting therapies. While a multitude of ARV7 detection approaches have been developed, the simultaneous enumeration of CTCs and assessment of ARV7 status and the integration of validated technologies for CTC enrichment/detection into their workflow render interpretation of the results more difficult and/or require shipment to centralized labs. Here, we describe the establishment and technical validation of a novel ARV7 detection method integrating the CellSearch® technology, the only FDA-cleared CTC-enrichment method for metastatic prostate cancer available so far. A highly sensitive and specific qPCR-based assay was developed, allowing detection of ARV7 and keratin 19 transcripts from as low as a single ARV7+/K19+ cell, even after 24 h of sample storage. Clinical feasibility was demonstrated on blood samples from 26 prostate cancer patients and assay sensitivity and specificity was corroborated. Our novel approach can now be included into prospective clinical trials aimed to assess the predictive values of CTC/ARV7 measurements in prostate cancer.
- Fatigue, quality of life and metabolic changes in men treated with first-line enzalutamide versus abiraterone plus prednisolone for metastatic castration-resistant prostate cancer (HEAT): a randomised trial protocol. [Journal Article]BMJ Open 2019; 9(9):e030218BO
- Enzalutamide and abiraterone acetate plus prednisolone (AAP) are used in combination with androgen-deprivation therapy to further suppress the androgen stimulation of metastatic castration-resistant prostate cancer (mCRPC). First-line mCRPC treatment with enzalutamide and AAP yields similar overall survival and radiographic progression-free survival in phase III trials. Thus, treatment selection …
Enzalutamide and abiraterone acetate plus prednisolone (AAP) are used in combination with androgen-deprivation therapy to further suppress the androgen stimulation of metastatic castration-resistant prostate cancer (mCRPC). First-line mCRPC treatment with enzalutamide and AAP yields similar overall survival and radiographic progression-free survival in phase III trials. Thus, treatment selection relies on patient choice, cost and side effects. The aim of this randomised trial is to investigate differences in fatigue, health-related quality of life (HRQoL) and metabolic side effects in men with mCRPC treated with first-line enzalutamide versus AAP.
- Quadriplegia secondary to abiraterone-induced severe hypokalemia. [Journal Article]South Asian J Cancer 2019 Jul-Sep; 8(3):139SA
- A prognostic score for overall survival in patients treated with abiraterone in the pre- and post-chemotherapy setting. [Journal Article]Oncotarget 2019; 10(49):5082-5091O
- CONCLUSIONS: Our study introduces a novel prognostic scoring-system for OS of real-life mCRPC patients receiving AA treatment irrespective of the line of therapy. The scoring-system is simple and can be easily utilized based on PSA and LDH values, neutrophil to lymphocyte ratio, and ECOG performance status.
- Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer. [Journal Article]Cancer 2019C
- CONCLUSIONS: PROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings.
- Results of a Real-world Study of Enzalutamide and Abiraterone Acetate With Prednisone Tolerability (REAAcT). [Journal Article]Clin Genitourin Cancer 2019CG
- CONCLUSIONS: Although baseline values were similar, more fatigue and neurocognitive differences were observed with ENZA compared with AA+P.
- Cost-effectiveness model of abiraterone plus prednisone, cabazitaxel plus prednisone and enzalutamide for visceral metastatic castration resistant prostate cancer therapy after docetaxel therapy resistance. [Journal Article]J Med Econ 2019; :1-8JM
- CONCLUSIONS: This analysis found ENZ provided greater LYs and QALYs than both ABI + PRD and CAB + PRD, at a lower cost than ABI + PRD, but at a higher cost compared to CAB + PRD. For patients with visceral mCRPC after docetaxel therapy resistance, ENZ was cost-effective 92% of the time with a WTP threshold of $100,000/QALY.
- Androgen Receptor Targeted Agents for Castration Resistant Prostate Cancer: A Review of Clinical Effectiveness and Cost-Effectiveness [BOOK]Canadian Agency for Drugs and Technologies in Health: Ottawa (ON)BOOK
- Prostate cancer is the most common cancer in men and is the fourth most common cancer in Canada.1 Approximately 1 in 7 men will be diagnosed with prostate cancer in their lifetime, and 1 in 27 will die from the disease.1,2 However, the age-standardized mortality rate for all stages of prostate cancer have decreased by an average of 2.9% per year, or 41.0% from 1995 to 2012.3,4 The majority (75%) …
Prostate cancer is the most common cancer in men and is the fourth most common cancer in Canada.1 Approximately 1 in 7 men will be diagnosed with prostate cancer in their lifetime, and 1 in 27 will die from the disease.1,2 However, the age-standardized mortality rate for all stages of prostate cancer have decreased by an average of 2.9% per year, or 41.0% from 1995 to 2012.3,4 The majority (75%) of diagnosed prostate cancer are stage I or stage II (localized), and the age-standardized incidence rate of these cancer stages have decreased by 3.2% per year from 2005 to 2015.4 The age-standardized incidence rate of stage III and IV cancers have remained relatively unchanged.4 Androgen deprivation therapy (ADT) has been the mainstay treatment for metastatic prostate cancer.5 Current ADT approaches include surgical castration or medical castration using a gonadotropin releasing hormone agonist with or without an anti-androgen drug.6 Although over 80% of patients respond to ADT initially, nearly all eventually develop progressive disease following castration, a lethal stage known as metastatic castration-resistant prostate cancer (mCRPC).7 In 2004, docetaxel (DTX) was the first chemotherapy approved by the US Food and Drug Administration for treatment of mCRPC.8,9 Since then, five newly developed agents were approved including a second generation taxane cabazitaxel (CTX),10 cellular immunotherapy sipuleucel-T,11 radiopharmaceutical radium-223,12 and two androgen receptor-targeted agents (ARTA) abiraterone acetate (AA)13–15 and enzalutamide (ENZ).16,17 Since ARTA have been demonstrated by recent studies in improving overall survival (OS) in both chemotherapy-pretreated and chemotherapy-naïve patients with mCRPC, both AA and ENZ have been approved as first-line treatment, instead of DTX.13–17 However, some patients have rapidly progressed on ARTA treatments despite the initial clinical effectiveness.18 After progression on first-line ARTA, it was unclear which subsequent therapy, such as second-line chemotherapy, an alternative ARTA, or an alternative ARTA with chemotherapy in between, would improve clinical outcomes. The aim of this report is to review the comparative clinical effectiveness and cost-effectiveness of varying treatment sequences of ARTA in patients with CRPC.
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- Abiraterone in "High-" and "Low-risk" Metastatic Hormone-sensitive Prostate Cancer. [Journal Article]Eur Urol 2019EU
- CONCLUSIONS: A total of 901 M1 STAMPEDE patients were evaluated after exclusions. Of the patients, 428 (48%) were identified as having a low risk and 473 (52%) a high risk. Patients receiving ADT + AAP had significantly improved OS (low-risk hazard ratio [HR]: 0.66, 95% confidence interval or CI [0.44-0.98]) and FFS (low-risk HR: 0.24, 95% CI [0.17-0.33]) compared with ADT alone. Heterogeneity of effect was not seen between low- and high-risk groups for OS or FFS. For OS benefit in low risk, the number needed to treat was four times greater than that for high risk. However, this was not observed for the other measured endpoints.Men with mHNPC gain treatment benefit from ADT + AAP irrespective of risk stratification for "risk" or "volume".