Alejo Rodriguez-Vida

Antitumour activity of enzalutamide (MDV3100) in patients with metastatic castration-resistant prostate cancer (CRPC) pre-treated with docetaxel and abiraterone.

BACKGROUND The new generation anti-androgen enzalutamide and the potent CYP17 inhibitor abiraterone have both demonstrated survival benefits in patients with metastatic castration-resistant prostate cancer (CRPC) progressing after docetaxel. Preliminary data on the antitumour activity of abiraterone after enzalutamide have suggested limited activity. The antitumour activity and safety of enzalutamide after abiraterone in metastatic CRPC patients is still unknown. PATIENTS AND METHODS We retrospectively identified patients treated with docetaxel and abiraterone prior to enzalutamide to investigate the activity and safety of enzalutamide in a more advanced setting. Prostate specific antigen (PSA), radiological and clinical assessments were analysed. RESULTS 39 patients with metastatic CRPC were identified for this analysis (median age 70years, range: 54-85years). Overall 16 patients (41%) had a confirmed PSA decline of at least 30%. Confirmed PSA declines of ⩾50% and ⩾90% were achieved in 5/39 (12.8%) and 1/39 (2.5%) respectively. Of the 15 patients who responded to abiraterone, two (13.3%) also had a confirmed ⩾50% PSA decline on subsequent enzalutamide. Among the 22 abiraterone-refractory patients, two (9%) achieved a confirmed ⩾50% PSA decline on enzalutamide. CONCLUSION Our preliminary case series data suggest limited activity of enzalutamide in the post-docetaxel and post-abiraterone patient population.

Is there an antiandrogen withdrawal syndrome with enzalutamide

To examine prostate‐specific antigen (PSA) levels after enzalutamide discontinuation to assess whether an antiandrogen withdrawal syndrome (AAWS) exists with enzalutamide.

Is there an anti-androgen withdrawal syndrome with enzalutamide?

To examine prostate‐specific antigen (PSA) levels after enzalutamide discontinuation to assess whether an antiandrogen withdrawal syndrome (AAWS) exists with enzalutamide.

enzalutamide for the treatment of metastatic castration-resistant prostate cancer

In recent years, several nonhormonal and hormonal agents, including enzalutamide, have been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC) on the basis of improved overall survival in prospective clinical trials. The incorporation of these agents has revolutionized the treatment of CRPC but has also raised the question of what is the ideal sequence of administering them. Enzalutamide is a nonsteroidal second-generation antiandrogen that has been approved for the treatment of metastatic CRPC both in the post-docetaxel and chemotherapy-naïve settings. This article reviews the pharmacological characteristics of enzalutamide, the efficacy studies which led to its approval, its safety profile, and quality of life-related parameters as well as its place in the sequential treatment and management of metastatic prostate cancer.

Causes of death in men with prostate cancer : an analysis of 50,000 men from the Thames Cancer Registry.

To investigate causes of death in a UK cohort of patients with prostate cancer.

Predictive and prognostic biomarkers of targeted agents and modern immunotherapy in renal cell carcinoma.

In the past decade, several agents targeting angiogenesis and signal transduction pathways have replaced the use of cytokines as standard of care treatment for metastatic renal cell carcinoma (RCC) after showing improved clinical benefit and survival. Currently, several novel immunotherapy agents targeting the programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) pathways are being tested in metastatic RCC and are bound to revolutionise the management of this disease. However, the success of both antiangiogenic drugs and new immunotherapy agents still depends on our ability to select patients most likely to respond to treatment. This article will review the current available evidence on prognostic and predictive biomarkers of response to signal transduction pathways-targeted agents and modern immunotherapy in metastatic RCC.

New treatment options for metastatic renal cell carcinoma

During the last decade, the treatment of advanced or metastatic renal cell carcinoma (RCC) was revolutionised with the advent of antiangiogenic drugs and tyrosine-kinase inhibitors. Several agents targeting the vascular endothelial growth factor (VEGF) pathway (sunitinib, bevacizumab, pazopanib, axitinib) or the mammalian target of rapamycin pathway (temsirolimus, everolimus) were since then progressively approved for first-line or later-line use in the treatment of patients with advanced RCC and became the new standard of care. As a result, the survival of patients with advanced RCC has significantly improved from a median overall survival of approximately 12 months in the cytokines era to more than 26 months with first-line VEGF inhibitors. During the two last years, the treatment of advanced RCC has witnessed a second revolution with the advent of immune checkpoint inhibitors, especially agents targeting the programmed cell death-1 receptor, as well as with the advent of new generation tyrosine-kinase receptor inhibitors. This article will review the new therapeutic options available for the treatment of advanced RCC, as well as the future potential molecular targets that are currently being investigated.

Precision medicine for prostate cancer

Metastatic castration-resistant prostate cancer remains a lethal disease despite considerable progress in systemic therapy over the past decade. The recent advances in genomic sequencing have improved the molecular classification of prostate cancer. The translation of genomic data into clinically relevant prognostic and predictive biomarkers to guide therapy is still in its infancy and therapies for castration-resistant prostate cancer are still used empirically. We discuss these genomic aberrations in more detail, focusing on androgen receptor signaling, ETS transcription factor gene rearrangements and PTEN loss. The incorporation of this genomic data within early phase clinical trials is evolving and may prove significant in advancing personalized care in prostate cancer.

Serum lipids as markers of prostate cancer occurrence and prognosis

Abstract With the current epidemic of lipid-related disorders and prostate cancer (PCa) in western countries, there is growing interest in the potential causal relationship between lipids and PCa. PCa is a heterogeneous disease, which undermines researchers’ ability to determine the mechanistic pathways responsible for its development and progression. Currently, detection and progression of PCa is mainly determined by prostate specific antigen, but this biomarker lacks specificity and is unable to discriminate between indolent and aggressive cancer. Nonetheless, there is evidence to suggest that lipid markers might potentially be useful in conjunction with other markers such as prostate specific antigen in improving detection and management of this disease. This review aims to highlight findings from epidemiological studies which examined the role of serum lipids in PCa occurrence and prognosis.

Cytoreductive nephrectomy: past, present and future

Cytoreductive nephrectomy (CN) is an integral part of the treatment of patients with metastatic renal cell carcinoma. Improved survival has been shown with CN and IFN-α. The introduction of targeted therapy for metastatic renal cell carcinoma has raised important questions regarding the role of CN. The majority of patients who were enrolled in the Phase III studies of targeted therapies had undergone prior nephrectomy. Thus, the benefit of these agents has largely been demonstrated in a nephrectomized population. CARMENA and SURTIME, important Phase III studies examining the role and timing of CN, are ongoing. Until new evidence is available, CN is a reasonable approach in selected patients with a resectable primary tumor and good performance status.