A phase Ib study of BKM120 combined with abiraterone acetate for castrate-resistant, metastatic prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 274-274 ◽  
Author(s):  
Akash Patnaik ◽  
Justin Kung ◽  
Massimo Loda ◽  
Mary-Ellen Taplin ◽  
Rosina Lis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Node ◽  
Combination Therapy ◽  
Metastatic Prostate Cancer ◽  
Single Agent ◽  
Pi3 Kinase ◽  
Primary Study ◽  
Pi3k Activation ◽  
Castrate Resistant ◽  
The Impact

274 Background: There is cross-talk between PI3-kinase (PI3K) pathway and androgen receptor (AR) signaling pathways, respectively, which are both critical for cell survival in castrate-resistant prostate cancer (CRPC). The primary study objective is to determine the safety profile and MTD of BKM120 (B, pan-PI3K inhibitor) in combination with abiraterone/prednisone (A/P) in CRPC patients. The secondary objectives are to assess the impact of PTEN status on duration of response/time to progression in the expansion cohort, and to evaluate the impact of B on a PI3-kinase activation fingerprint in metastatic bone or lymph node tissue samples. An exploratory objective is to assess the effect of B on transcription of a set of AR-regulated genes in metastatic bone biopsy samples. Methods: The trial design involves a 14 day lead-in phase with B alone, to assess single-agent toxicity and perform correlative studies. A/P is combined with B at the end of 14 days using the standard 3+3 dose-escalation design with 3 dose levels of B, and participants are assessed for safety and MTD on the combination therapy. To determine PD impact of single agent B on the PI3K activation signature at a metastatic site, a mandatory CT-guided bone or lymph node biopsy is performed prior to B initiation and at the end of 2 weeks on B single-agent therapy. Immunohistochemical (IHC) stains for three markers (p-AKT, p-S6 and PTEN) are used to obtain a semi-quantitative PI3K activation score, based on the quartile levels of continuous staining scores of each marker. Results: Patient 1 had symptomatic bone pain improvement, marked decline in narcotic pain requirements and a biochemical decline in PSA from 156.5 to a PSA nadir of 9.2 within 4 weeks of combination therapy. Patient 3 had a symptomatic and >90% biochemical improvement and has currently completed 15 cycles on treatment, and remains on study to date. RT-PCR analysis showed that the feedback circuitry between PI3K and AR signaling is heterogeneous in the metastatic prostate cancer-bone microenvironment, and dependent on tumor PTEN status. Conclusions: Preliminary data shows promising anti-tumor activity in CRPC patients from dual targeting of PI3K and AR pathways with B and A/P, respectively. Clinical trial information: NCT01741753.

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

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.

scholarly journals Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e042953
Author(s):  
Martin John Connor ◽  
Taimur Tariq Shah ◽  
Katarzyna Smigielska ◽  
Emily Day ◽  
Johanna Sukumar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Node ◽  
Androgen Receptor ◽  
Randomised Controlled Trial ◽  
Phase Ii ◽  
Metastatic Prostate Cancer ◽  
Controlled Trial ◽  
Pelvic Lymph Node ◽  
Study Results ◽  
Randomised Controlled

IntroductionSurvival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone.MethodsA phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. Primary outcome: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024.Ethics and disseminationApproved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03763253; ISCRTN58401737

Quantification of tumor cell burden by analysis of single cell lymph node disaggregates in metastatic prostate cancer

The Prostate ◽  
2010 ◽  
Vol 70 (10) ◽  
pp. 1110-1118 ◽  
Author(s):  
David Schilling ◽  
Joerg Hennenlotter ◽  
Karl Sotlar ◽  
Ursula Kuehs ◽  
Erika Senger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Node ◽  
Tumor Cell ◽  
Single Cell ◽  
Metastatic Prostate Cancer

Associations of pre-existing cardiovascular disease (CVD) with treatment patterns and survival outcomes in patients with metastatic prostate cancer: A real-world, population-based study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17056-e17056
Author(s):  
Atul Batra ◽  
Shiying Kong ◽  
Winson Y. Cheung
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Population Based ◽  
Treatment Patterns ◽  
Survival Outcomes ◽  
Administrative Claims ◽  
World Population ◽  
Cancer Treatments ◽  
Lower Likelihood ◽  
The Impact

e17056 Background: Prior cardio-oncology research has focused on examining the future risk of CVD as a result of cancer treatments. The impact of pre-existing CVD on cancer treatments is less clear. This study aimed to identify the associations of baseline CVD on treatment patterns and survival outcomes in metastatic prostate cancer where older age and exposure to androgen deprivation therapy can potentiate cardiac risks. Methods: We identified all patients diagnosed with metastatic prostate cancer in a large Canadian province from 2004 to 2017 using the population-based cancer registry. Administrative claims were linked to ascertain any diagnoses of pre-existing CVD, defined as any of arrythmias [AR], cerebrovascular accidents [CVAs], myocardial infarctions [MIs], or congestive heart failure [CHF] that preceded the diagnosis of metastatic prostate cancer. Logistic and Cox regression models were constructed to determine the associations of baseline CVD with receipt of cancer treatments (such as radiation, or systemic therapy) and overall survival (OS). Results: A total of 3,257 patients were included. The median age was 66 years (interquartile range, 46-95 years). At diagnosis of advanced prostate cancer, 993 (30.5%) had pre-existing CVD: 10.0% AR, 4.3% CVAs, 3.0% MIs, 2.8% CHF and 10.4% multiple CVDs. The Charlson comorbidity index (CCI) was 0, 1 and >1 in 53.4%, 27.3% and 19.3%, respectively. Overall, 2078 (63.8%) patients received chemotherapy, while 747 (22.9%) received radiotherapy. After adjusting for age and CCI, pre-existing CVD was associated with a lower likelihood of chemotherapy (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.61-0.75; P=0.001) and radiotherapy (OR, 0.87; 95% CI, 0.85-0.91; P<0.001). Likewise, CVD was associated with worse OS, after adjusting for measured confounding variables (see table). Conclusions: One-third of patients with metastatic prostate cancer had pre-existing CVD, which was associated with a lower likelihood of chemotherapy and worse OS. In the context of an aging general population, early cardio-oncology consultations to optimize CVD management may lead to safer and broader uptake of appropriate prostate cancer treatments.[Table: see text]

scholarly journals Management of Advanced and Metastatic Prostate Cancer: A Need for a Sub-Saharan Guideline

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ayun Cassell ◽  
Bashir Yunusa ◽  
Mohamed Jalloh ◽  
Medina Ndoye ◽  
Mouhamadou M. Mbodji ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Metastatic Prostate Cancer ◽  
Cost Effective ◽  
Androgen Deprivation ◽  
Sub Saharan Africa ◽  
International Agency ◽  
Castrate Resistant Prostate Cancer ◽  
Sub Saharan ◽  
Castrate Resistant

The estimated incidence rate of prostate cancer in Africa was 22.0/100,000 in 2016. The International Agency for Research on Cancer (IARC) has cited prostate cancer as a growing health threat in Africa with approximated 28,006 deaths in 2010 and estimated 57,048 deaths in 2030. The exact incidence of advanced and metastatic prostate cancer is not known in sub-Saharan Africa. Hospital-based reports from the region have shown a rising trend with most patients presenting with advanced or metastatic disease. The management of advanced and metastatic prostate cancer is challenging. The available international guidelines may not be cost-effective for an African population. The most efficient approach in the region has been surgical castration by bilateral orchidectomy or pulpectomy. Medical androgen deprivation therapy is expensive and may not be available. Patients with metastatic castrate-resistant prostate cancer tend to be palliated due to the absence or cost of chemotherapy or second-line androgen deprivation therapy in most of Africa. A cost-effective guideline for developing nations to address the rising burden of advanced prostate cancer is warranted at this moment.

scholarly journals Estudo Unicêntrico Prospetivo de Avaliação Sistemática da Dor em Doentes Portugueses com Cancro da Próstata Metastizado

2017 ◽  
Vol 30 (11) ◽  
pp. 796
Author(s):  
Maria Inês Sequeira ◽  
Nuno Sousa ◽  
Maria Fragoso ◽  
Alexandra Silva ◽  
Filipa Pereira ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Pain Intensity ◽  
Metastatic Prostate Cancer ◽  
Short Form ◽  
Brief Pain Inventory ◽  
Life Assessment ◽  
Medical Interventions ◽  
Reduction Of Pain ◽  
Prevalence Of Pain ◽  
The Impact

Introduction: Pain is one of the most common symptoms reported by cancer patients and is associated with decreased quality of life. Assessment of pain with standardized questionnaires reduces variability in its interpretation and may increase effectiveness of medical interventions. Prostate cancer is the most frequent male neoplasm in Portugal. We designed this study to evaluate the impact of a standardized pain questionnaire on pain management in patients with metastatic prostate cancer.Material and Methods: Single centre prospective observational study of patients with metastatic prostate cancer. The study was designed to evaluate the benefit of systematically evaluating pain with Brief Pain Inventory-Short Form prior to a scheduled medical oncology consult. Patients reporting pain were reassessed one week later by telephone. To assess the benefit two consecutive cohorts were established based on communication of questionnaire results to the treating physician.Results: We recruited 207 patients of which 60% reported pain. Statistically significant decrease in mean pain intensity one week after the scheduled appointment was noted (3.95 vs 3.01; p < 0.001). Patients whose Brief Pain Inventory-Short Form was provided to their oncologist experienced greater reduction in pain, which was non-significant (p = 0.227). Using Brief Pain Inventory-Short Form assessment resulted in a higher probability of pain control (43.5% vs 30.9%; p = 0.193).Discussion: The prevalence of pain founded was higher than described in the literature, probably because our sample was less selected than the published in clinical trials. After the scheduled appointment, there was a statistically significant reduction in mean pain intensity, but the explicit use of this questionnaire was not associated with a statistically significant reduction of pain.Conclusion: Patients with metastatic prostate cancer have a high prevalence of pain. Evaluation and treatment by medical oncologists is associated with a reduction of mean pain intensity. The use of Brief Pain Inventory-Short Form was associated with a non-significant increased reduction of pain.

Contemporary Trends and Survival Outcomes After Aborted Radical Prostatectomy in Lymph Node Metastatic Prostate Cancer Patients

2019 ◽  
Vol 5 (3) ◽  
pp. 381-388 ◽  
Author(s):  
Marco Bandini ◽  
Felix Preisser ◽  
Sebastiano Nazzani ◽  
Michele Marchioni ◽  
Zhe Tian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Node ◽  
Radical Prostatectomy ◽  
Cancer Patients ◽  
Metastatic Prostate Cancer ◽  
Survival Outcomes
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