Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The changing landscape of treatment options for metastatic castrate-resistant prostate cancer: challenges and solutions for physicians and patients.

ABSTRACT: Four recently approved drugs (cabazitaxel, sipuleucel-T, abiraterone, and denosumab), along with emerging therapies, bone-building therapies, hormonal treatments, and immunotherapies, have all demonstrated promise in advanced prostate cancer. It appears that the best outcomes will be achieved from the sequential use of multiple agents.

SUBMITTER: Chrvala CA

PROVIDER: S-EPMC3474424 | biostudies-other | 2012 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

The changing landscape of treatment options for metastatic castrate-resistant prostate cancer: challenges and solutions for physicians and patients.

Chrvala Carole Alison CA

P & T : a peer-reviewed journal for formulary management 20120801 8

Four recently approved drugs (cabazitaxel, sipuleucel-T, abiraterone, and denosumab), along with emerging therapies, bone-building therapies, hormonal treatments, and immunotherapies, have all demonstrated promise in advanced prostate cancer. It appears that the best outcomes will be achieved from the sequential use of multiple agents. ...[more]

PMID: 23091338

Similar Datasets

Evolving landscape and novel treatments in metastatic castrate-resistant prostate cancer.

Project description:Treatment options for castrate-resistant prostate cancer (CRPC) have advanced in recent years and significantly improved the outlook for patients with this aggressive and lethal disease. Further understanding of the biology of CRPC has led to several new targeted therapies and continues to emphasize the importance of androgen receptor (AR) directed therapy. The treatment landscape is rapidly changing and further biologically rationale, biomarker-based ongoing clinical trials are needed. We review the recent results of major clinical trials in CRPC. New and investigational agents now in clinical evaluation are reviewed including inhibitors of angiogenesis, microtubules, chaperones, AR and intracellular kinases, as well as immunotherapy, radiopharmaceuticals and bone-targeted agents. The recent improvement in prognosis for CRPC brings continued optimism for further improvements. Thoughtful planning of clinical trials and further understanding of the mechanisms of resistance to therapies will allow for continued progress in patient care.

| S-EPMC3739642 | biostudies-literature

Challenges to improved therapeutics for metastatic castrate resistant prostate cancer: from recent successes and failures.

Project description:Men with metastatic castration-resistant prostate cancer (mCRPC) carry poor prognosis despite the use of docetaxel-based regimens which has modest survival benefit shown by randomized clinical trials. Significant progress in the discovery of novel therapeutic agents has been made in the past few years. While sipuleucel-T, cabazitaxel, and abiraterone gained regulatory approval in 2010 and 2011, several highly promising candidates/regimens have failed in large scale clinical trials. Challenges remain to optimize the design and interpretation of clinical trial results and develop more effective strategies for mCRPC. In this review, we examined the positive and negative clinical trials in mCRPC in the past and discussed the various aspects of clinical trial design including selection of targets and appropriate outcome measures, biomarker development and implementation, and strategies for combination therapy.

| S-EPMC3425086 | biostudies-literature

Novel therapies for metastatic castrate-resistant prostate cancer.

Project description:Recent advances in tumor biology have made remarkable achievements in the development of therapy for metastatic castrate-resistant prostate cancer. These advances reflect a growing appreciation for the role of the tumor microenvironment in promoting prostate cancer progression. Prostate cancer is no longer viewed predominantly as a disease of abnormally proliferating epithelial cells but rather as a disease of complex interactions between prostate cancer epithelial cells (epithelial compartment) and the surrounding tissues (stromal compartment) in which they reside. For example, prostate cancers frequently metastasize to bone, an organ that contains a microenvironment rich in extracellular matrix proteins and stromal cells including hematopoietic cells, osteoblasts, osteoclasts fibroblasts, endothelial cells, adipocytes, immune cells, and mesenchymal stem cells. Multiple signaling pathways provide crosstalk between the epithelial and the stromal compartments to enhance tumor growth, including androgen receptor signaling, tyrosine kinase receptor signaling, and immune surveillance. The rationale to disrupt this "two-compartment" crosstalk has led to the development of drugs that target tumor stromal elements in addition to the cancer epithelial cell.

| S-EPMC4176261 | biostudies-literature

The changing landscape in the treatment of metastatic castration-resistant prostate cancer.

Project description:The past few years have brought increasing advances in the therapeutic management of metastatic castration-resistant prostate cancer with the approval of several agents, including vaccine therapy with sipuleucel-T, second-line chemotherapy with cabazitaxel, the bone-targeted pharmaceutical denosumab, and the novel antiandrogen therapy abiraterone acetate. There are ongoing developments with other agents in the pipeline such as MDV3100 and alpharadin that have shown promising results. This review describes the clinical trials that brought about the drug approvals of various agents and offers some insights regarding a rational approach to optimal treatment sequencing for these drugs since national guidelines are currently lacking.

| S-EPMC3539272 | biostudies-literature

Enzalutamide-resistant castration-resistant prostate cancer: challenges and solutions.

Project description:The new-generation hormonal agent enzalutamide has been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC), in both post- and predocetaxel setting, due to the significant improvement in overall survival. More recently, enzalutamide also showed impressive results in the treatment of men with nonmetastatic CRPC. Unfortunately, not all patients with CRPC are responsive to enzalutamide, and even in responders, benefits are limited by the development of drug resistance. Adaptive resistance of metastatic prostate cancer to enzalutamide treatment can be due to the activation of both androgen receptor (AR)-dependent pathways (expression of constitutively active AR splice variants, AR point mutations, gene amplification and overexpression) and mechanisms independent of AR signaling pathway (altered steroidogenesis, upregulation of the glucocorticoid receptor, epithelial-mesenchymal transition, neuroendocrine transformation, autophagy and activation of the immune system). In this review, we focus on resistance mechanisms to enzalutamide, exploring how we could overcome them through novel therapeutic options.

| S-EPMC6204864 | biostudies-literature

Novel Target Opportunities in Non-Metastatic Castrate Resistant Prostate Cancer.

Project description:Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay; however, some patients will transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC may develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, however, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.

| S-EPMC8157020 | biostudies-literature

Radium-223 in Heavily Pretreated Metastatic Castrate-Resistant Prostate Cancer.

Project description:BackgroundRadium-223 is a bone-targeting radiopharmaceutical that extends survival in mCRPC. Postapproval data are limited, and the value of biochemical and radiologic monitoring during radium therapy is unknown.Patients and methodsWe conducted a retrospective study of 29 patients with mCRPC who received radium-223 at 1 of 3 participating institutions between August 2013 and December 2014. Trend of PSA, radiographic changes, and association of biochemical and clinical variables with PSA trend were measured.ResultsThe median age of patients was 70 years, 79% of patients (N = 23) were European Americans, and 17% of patients (N = 5) were African Americans. Twenty patients (69%) had received at least 3 lines of prior therapies. Some 38% of patients (N = 11) received all 6 cycles of radium-223. Twenty patients (69%) had an increase in PSA during radium therapy, and 4 patients (14%) had a decline in PSA levels. Five patients had visceral metastases on computed tomography imaging performed during the course of radium-223.ConclusionsRadium therapy in mCRPC was associated with an increase in PSA in the majority of these heavily pretreated patients. The development of visceral disease was not uncommon, suggesting a need for follow-up computed tomography monitoring during radium-223 therapy. The significance of early increases in PSA and pain with radium-223 is still uncertain. Although pain and PSA flare have been reported in patients who subsequently have a dramatic response to therapy, we observed that a PSA increase or pain flare correlates to an improvement in bone scans only in a minority of patients.

| S-EPMC6849387 | biostudies-literature

Pembrolizumab in men with heavily treated metastatic castrate-resistant prostate cancer.

Project description:BACKGROUND:Pembrolizumab is approved for patients with metastatic, microsatellite instability (MSI)-high or mismatch repair-deficient (dMMR) solid tumors. However, very few men with prostate cancer were included in these initial studies. METHODS:We performed a single institution retrospective review of men with metastatic castrate-resistant prostate cancer (mCRPC) who were treated with pembrolizumab. The primary objective was to describe the clinical efficacy of pembrolizumab associated with patient and genomic characteristics. RESULTS:We identified 48 men who received ?1 cycle of pembrolizumab for mCRPC. Of these, 94% (45/48) had ?3 prior lines of therapy for mCRPC. Somatic tumor sequencing was available in 18/48 men (38%). We found that 17% (8/48) had a ?50% confirmed PSA decline with pembrolizumab, and 8% (4/48) had a ?90% PSA decline with durations of response ranging from 3.1 to 16.3 months. Two of these four men had mutations in LRP1b, one of whom also had MSH2 loss and was MSI-H and TMB-high. Despite prior progression on enzalutamide, 48% (23/48) of men were treated with concurrent enzalutamide. The median PSA progression-free-survival was 1.8 months (range 0.4-13.7 months), with 31% of patients remaining on pembrolizumab therapy and 54% of men remain alive with a median follow-up of 7.1 months. CONCLUSIONS:In a heavily pretreated population of men with mCRPC, pembrolizumab was associated with a ?50% PSA decline in 17% (8/48) of men, including a dramatic ?90% PSA response in 8% (4/48), two of whom harbored pathogenic LRP1b mutations suggesting that LRP1b mutations may enrich for PD-1 inhibitor responsiveness in prostate cancer.

| S-EPMC6712455 | biostudies-literature

Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer.

Project description:Abiraterone treats metastatic castrate-resistant prostate cancer by inhibiting CYP17A, an enzyme for testosterone auto-production. With standard dosing, evolution of resistance with treatment failure (radiographic progression) occurs at a median of ~16.5 months. We hypothesize time to progression (TTP) could be increased by integrating evolutionary dynamics into therapy. We developed an evolutionary game theory model using Lotka-Volterra equations with three competing cancer "species": androgen dependent, androgen producing, and androgen independent. Simulations with standard abiraterone dosing demonstrate strong selection for androgen-independent cells and rapid treatment failure. Adaptive therapy, using patient-specific tumor dynamics to inform on/off treatment cycles, suppresses proliferation of androgen-independent cells and lowers cumulative drug dose. In a pilot clinical trial, 10 of 11 patients maintained stable oscillations of tumor burdens; median TTP is at least 27 months with reduced cumulative drug use of 47% of standard dosing. The outcomes show significant improvement over published studies and a contemporaneous population.

| S-EPMC5703947 | biostudies-literature

Sequencing of cabazitaxel in metastatic castrate-resistant prostate cancer: a case report.

Project description:Prostate cancer is a common cancer in men; for metastatic disease, it has a 5-year survival rate of 30%. No FDA-approved therapy for castrate-resistant prostate cancer (CRPC) known to improve survival was available until 2004, when based on a significant survival benefit over mitoxantrone, docetaxel in combination with prednisone was approved. In combination with prednisone, cabazitaxel, which was approved in the United States in 2010, is indicated for patients with metastatic CRPC previously treated with a docetaxel-containing regimen. This case report describes the treatment of a man 58 years of age who was diagnosed with advanced prostate cancer in 2006. He was initially managed with radical prostatectomy followed by androgen deprivation therapy, but a rising prostate-specific antigen (PSA) level led to enrollment in a clinical trial of HE3235 for 6 months. Subsequently, with progression of disease, he was treated with docetaxel for 4 months and then palliative radiation therapy. Cabazitaxel was initiated in October 2010; his condition stabilized within weeks, and he experienced a progressive decline in his PSA level from a peak of 5,424 ng/ml. Continued treatment with cabazitaxel resulted in his being weaned off pain medications and resuming his normal activities. After 16 cycles of cabazitaxel, his PSA declined to 994 ng/ml as of January 2012. He tolerated the cabazitaxel well and occasionally received myeloid growth factors for treatment of neutropenia; otherwise, he experienced only mild diarrhea. This response to cabazitaxel is notable, particularly in light of prior failure of multiple therapies.

| S-EPMC3398088 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data