Real world outcomes of upfront docetaxel for hormone naïve metastatic prostate cancer in an ethnically diverse inner-city population.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 359-359
Author(s):  
Surabhi Pathak ◽  
Romy Jose Thekkekara ◽  
Ahmed T Ahmed ◽  
Udit Yadav ◽  
Michael Russell Mullane ◽  
...  

359 Background: Upfront docetaxel (UD) in castration-sensitive metastatic prostate cancer (CSPC) has improved failure-free and overall survival in the CHAARTED, GETUG-AFU 15 and STAMPEDE trials, resulting in a paradigm shift in practice patterns. However, the impact of docetaxel-based chemotherapy regimens in minorities and in real-world practice remains to be described. The objective of this study is to evaluate tolerability and response to UD in an inner-city ethnically diverse CSPC cohort. Methods: We retrospectively reviewed clinical data for CSPC patients at Cook County Hospital. Patients treated with UD and androgen deprivation (UD, n = 49, 2013-17) were compared to those receiving androgen deprivation alone (ADT, n = 42, 2010-17) using descriptive statistics and Cox Proportional Hazards analysis. Results: Median age was 59 and 60 years in UD and ADT, respectively. African Americans, Hispanics and Caucasians formed 69%, 18%, and 10% in UD and 64%, 9.5% and 26% in ADT. Median PSA at diagnosis was: UD 536 [72-1110] ng/ml, ADT 229 [54-999] ng/ml (p = 0.3). Gleason score > 7 was present in 89.8% [UD] and 92.8% [ADT]. UD and ADT had similar frequency of bone (91% vs. 95%, p = 0.5), visceral (12.2% vs. 11.9%, p = 0.9) and retroperitoneal nodal metastases (55% vs. 45.2%, p = 0.3). UD was initiated a median of 8 weeks from diagnosis. 94% in UD received > 3 cycles of chemotherapy. CTCAE grade > 3 events included anemia (6%); neutropenia (6%); infection (4%); diarrhea (4%); peripheral neuropathy (6%), and fatigue (2%). Median PSA nadir was 3.2 [0.5-40.1] vs. 3.45 [0.1-36.4] ng/ml and time to nadir was 20 [13-27] vs. 41 [19-69] weeks in UD vs. ADT. Biochemical progression was observed in 34.7% [UD] vs. 40.5% [ADT]. Median time to castration-resistance was UD: 39 [31-67] vs. ADT: 65 [34-76] weeks [HR: 0.9; 95% CI 0.4-1.8; p = 0.7]. There were 12 deaths [UD: 4; ADT: 8] during a median follow-up of 46 [23-86, UD] and 111 [68-157, ADT] weeks. Conclusions: In a diverse underserved population with CSPC, UD was well tolerated but was not associated with improvement in time to castration compared to ADT. These results warrant validation and underscore the importance of ensuring accrual of minorities in clinical trials.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 289-289 ◽  
Author(s):  
Warner Finstad ◽  
Raimundas Galiauskas ◽  
James Cook ◽  
Kate Murphy ◽  
Derbrenn O'Connor ◽  
...  

289 Background: Patients with metastatic prostate cancer receive several therapies which may be associated with a tendency to overweight and impaired glucose tolerance. These include androgen deprivation therapy and long term steroid therapy. We set out to assess the prevalence of overweight and diabetes/prediabetes in a cohort of patients attending an oncology day ward for a variety of systemic therapies. Methods: We performed a retrospective review of the medical records of men attending an oncology day ward for prostate cancer treatment. As part of their usual care, these men had regular height and weight checks and also had periodic hemoglobin A1C (HbA1C) measurements performed. The prevalence of prediabetes and diabetes in this patient population was assessed from the HbA1C results using the American Diabetes Association 2016 definitions. Information on patient steroid use (and type), and treatment type were also recorded. Results: Among 34 men with metastatic prostate cancer, the mean age was 74 (range 57-88). Therapies received included androgen deprivation therapy in all cases, with chemotherapy or novel androgen receptor pathway inhibitors such as abiraterone and enzalutamide. Only 12% had a pre-existing diagnosis of diabetes mellitus (all type 2). The majority (79%) are overweight or obese. 59% have pre-diabetes as per the American Diabetes Association 2016 Guidelines, while a further 24% meet criteria for diabetes. Only 18% have HbA1c in the normal range. 56% are on continuous long term steroid therapy, usually as part of their prostate cancer therapy. A further 23% receive intermittent steroids. Only 21% had received no steroids in the 6 months prior to first HbA1C check. 18% had castrate-sensitive disease and 82% had castrate resistant disease. Even among patients with castrate sensitive disease, 2/3 had abnormal HbA1c values. Conclusions: Overweight and prediabetes are very prevalent in men receiving systemic therapies for metastatic prostate cancer. A large percentage of men are on long-term steroid therapy which may be contributing to their risk of these conditions. Intervention is required for this group of patients to reduce the impact of therapy on cardiovascular and overall health.


2017 ◽  
Vol 2 (3) ◽  
pp. 41-46
Author(s):  
Jimpei Miyakawa ◽  
Satoru Taguchi ◽  
Motofumi Suzuki ◽  
Kaori Endo ◽  
Yorito Nose ◽  
...  

Background: While semiannual 60 mg denosumab is a common treatment for osteoporosis, impact of monthly 120 mg denosumab, the common treatment protocol for bone metastases from solid tumors, on bone metabolism is unclear.Materials and Methods: We reviewed 15 patients with bone-metastatic prostate cancer who initiated monthly 120 mg denosumab in conjunction with androgen deprivation therapy between 2013 and 2014. Bone mineral density (BMD) was measured at lumbar spine and femoral neck using dual energy X-ray absorptiometry (DXA), before treatment and annually thereafter. Bone metabolism markers, including urine N-terminal telopeptide (uNTx) and bone type alkaline phosphatase (BAP), were monitored monthly.Results: Twelve of 15 (80%) patients had evaluable DXA before treatment, and of them, eight underwent DXA after a year of initiation without discontinuation of denosumab. Percent changes in BMD from baseline were +6.2% at lumbar spine and +7.6% at femoral neck, both of which were significant increases (both P<0.01). Bone metabolism markers were evaluable in 11 (73%) patients: uNTx decreased rapidly, while BAP declined gradually after initiating denosumab. These effects were similar to those seen by the standardized dose for osteoporosis in previous literature. There were no denosumab-related severe adverse events during the follow-up period. Conclusions: The impact of monthly 120 mg denosumab on bone metabolism was significant, but almost equivalent to that of the standard dose for osteoporosis (60mg semiannually) in bone-metastatic prostate cancer undergoing androgen deprivation therapy. Whereas the higher dose has reportedly reduced skeleton-related events, the effect on bone metabolism seemed plateaued or showed no dose-dependency.


2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e17038-e17038
Author(s):  
Surabhi Pathak ◽  
Romy Jose Thekkekara ◽  
Ahmed T Ahmed ◽  
Udit Yadav ◽  
Michael Russell Mullane ◽  
...  

2017 ◽  
Vol 11 (1-2) ◽  
pp. 16 ◽  
Author(s):  
Laurence Klotz ◽  
Rodney H. Breau ◽  
Loretta L. Collins ◽  
Martin E. Gleave ◽  
Tom Pickles ◽  
...  

Introduction: Testosterone suppression, or androgen-deprivation therapy (ADT), is an established treatment for recurrent and metastatic prostate cancer (PCa). Based on the accuracy and sensitivityof early assays (c. 1960–1970), the castrate testosterone level was set at ≤1.7 nmol/l. Improved sensitivity of testosterone assays shows that both surgical and medical castration can achieve levels <0.7 nmol/l. However, the clinical implications and importance of maximum testosterone suppression remains a subject of controversy. This evidence-based review assesses prospective and retrospectiveclinical data, linking maximum suppression of testosterone with improved outcomes from ADT.Methods: PubMed and conference proceedings were searched for studies assessing the impact of low testosterone on clinical outcomes from ADT. The key search terms included combinations of prostate cancer and testosterone, predictive/prognostic, and androgen deprivation. Results were limited to studies investigating the relationship between testosterone levels and clinical outcomes.Results: Both prospective and retrospective data support a relationship between testosterone levels below the historical standard of 1.7 nmol/l and improved outcomes. Eight studies showed significantimprovements in survival-related outcomes, with the majority of data supporting a testosterone level cutoff of ≤0.7 nmol/l.Conclusions: Tracking both testosterone and prostate-specific antigen (PSA) levels has significant clinical benefits, and the serum testosterone threshold of ≤0.7 nmol/l is a practical goal. The relativelevels of testosterone and PSA may indicate continued hormone responsiveness or progression toward castration-resistant prostate cancer (CRPC) and should, therefore, inform treatment strategy. Standardization of assay methods and clinical coordination to facilitate widespread access to state-of the art laboratory equipment is necessary to ensure accurate decision-making.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paula Kappler ◽  
Michael A. Morgan ◽  
Philipp Ivanyi ◽  
Stefan J. Brunotte ◽  
Arnold Ganser ◽  
...  

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.


BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e043844
Author(s):  
Natalia Araujo ◽  
Samantha Morais ◽  
Ana Rute Costa ◽  
Raquel Braga ◽  
Ana Filipa Carneiro ◽  
...  

IntroductionProstate cancer is the most prevalent oncological disease among men in industrialised countries. Despite the high survival rates, treatments are often associated with adverse effects, including metabolic and cardiovascular complications, sexual dysfunction and, to a lesser extent, cognitive decline. This study was primarily designed to evaluate the trajectories of cognitive performance in patients with prostate cancer, and to quantify the impact of the disease and its treatments on the occurrence of cognitive decline.MethodsParticipants will be recruited from two main hospitals providing care to approximately half of the patients with prostate cancer in Northern Portugal (Portuguese Institute of Oncology of Porto and São João Hospital Centre), and will comprise a cohort of recently diagnosed patients with prostate cancer proposed for different treatment plans, including: (1) radical prostatectomy; (2) brachytherapy and/or radiotherapy; (3) radiotherapy in combination with androgen deprivation therapy and (4) androgen deprivation therapy (with or without chemotherapy). Recruitment began in February 2018 and is expected to continue until the first semester of 2021. Follow-up evaluations will be conducted at 1, 3, 5, 7 and 10 years. Sociodemographic, behavioural and clinical characteristics, anxiety and depression, health literacy, health status, quality of life, and sleep quality will be assessed. Blood pressure and anthropometrics will be measured, and a fasting blood sample will be collected. Participants’ cognitive performance will be evaluated before treatments and throughout follow-up (Montreal Cognitive Assessment and Cube Test as well as Brain on Track for remote monitoring). All participants suspected of cognitive impairment will undergo neuropsychological tests and clinical observation by a neurologist.Ethics and disseminationThe study was approved by the Ethics Committee of the hospitals involved. All participants will provide written informed consent, and study procedures will be developed to ensure data protection and confidentiality. Results will be disseminated through publication in peer-reviewed journals and presentation in scientific meetings.


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