Treatment, healthcare resource utilization, and costs associated with non-metastatic and metastatic castration-resistant prostate cancer: A claims analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18341-e18341 ◽  
Author(s):  
Adriana Valderrama ◽  
Krishna Tangirala ◽  
Svetlana Babajanyan ◽  
Sreevalsa Appukkuttan ◽  
Lonnie Kent Wen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Resource Utilization ◽  
Healthcare Resource ◽  
Management Strategies ◽  
Baseline Period ◽  
Healthcare Resource Utilization ◽  
Castration Resistant Prostate Cancer ◽  
Before And After ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

e18341 Background: Limited evidence exists about economic burden in non-metastatic castrate resistant prostate cancer (nmCRPC). The aim of this study was to describe the real-world treatments in this setting and to quantify both the costs and healthcare resource utilization (HCRU) during the year before and after metastasis for this patient population. Methods: A retrospective cohort of metastatic castrate resistant prostate cancer (mCRPC) patients was identified from Truven Health MarketScan database from January 2009 to March 2015 with metastasis diagnosis as index date. mCRPC algorithm was based on ICD-9 codes for both prostate cancer and secondary metastatic disease, and a subsequent claim for a FDA approved treatment for mCRPC. Patients were also required to have evidence of surgical or medical castration in the baseline period to define nmCRPC. Costs and HCRU were compared in the 1 year pre- and post-index time periods. Results: Among 341 mCRPC patients identified, mean age was 71.9 years (72.4% ≥65 years old), 72.7% were Medicare Advantage patients and 19.4% had Klabunde comorbidity > 1. Most common treatments in the pre index period were bicalutamide (90%), leuprolide (83.6%), docetaxel (27.6%), abiraterone (22.9%) and ketoconazole (21.4%). Mean per patient per year (PPPY) all cause HCRU and costs were significantly higher (all P < 0.05) in the mCRPC patients compared to nmCRPC patients (Table). Conclusions: Average yearly costs more than doubled following mCRPC diagnosis, which indicates the need for appropriate management strategies for nmCRPC patients in order to optimize the potential delay of disease progression. [Table: see text]

scholarly journals Titration of Androgen Signaling: How Basic Studies Have Informed Clinical Trials Using High-Dose Testosterone Therapy in Castrate-Resistant Prostate Cancer

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 884
Author(s):  
Steven K. Nordeen ◽  
Lih-Jen Su ◽  
Gregory A. Osborne ◽  
Perry M. Hayman ◽  
David J. Orlicky ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Dose ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Ablation ◽  
Clinical Observations ◽  
Clinical Benefits ◽  
Castrate Resistant Prostate Cancer ◽  
Prostate Cancers ◽  
Castrate Resistant ◽  
Basic Studies

Since the Nobel Prize-winning work of Huggins, androgen ablation has been a mainstay for treatment of recurrent prostate cancer. While initially effective for most patients, prostate cancers inevitably develop the ability to survive, grow, and metastasize further, despite ongoing androgen suppression. Here, we briefly review key preclinical studies over decades and include illustrative examples from our own laboratories that suggest prostate cancer cells titrate androgen signaling to optimize growth. Such laboratory-based studies argue that adaptations that allow growth in a low-androgen environment render prostate cancer sensitive to restoration of androgens, especially at supraphysiologic doses. Based on preclinical data as well as clinical observations, trials employing high-dose testosterone (HDT) therapy have now been conducted. These trials suggest a clinical benefit in cancer response and quality of life in a subset of castration-resistant prostate cancer patients. Laboratory studies also suggest that HDT may yet be optimized further to improve efficacy or durability of response. However, laboratory observations suggest that the cancer will inevitably adapt to HDT, and, as with prior androgen deprivation, disease progression follows. Nonetheless, the adaptations made to render tumors resistant to hormonal manipulations may reveal vulnerabilities that can be exploited to prolong survival and provide other clinical benefits.

Studies of a novel modified E2F-targeted peptide with activity against castration-resistant prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 205-205
Author(s):  
Joseph R. Bertino ◽  
Zoltan Szekely ◽  
Kathleen W Scotto
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Replication Proteins ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
The Stability

205 Background: The E2F family of genes encodes transcription factors that are key to the regulation of a number of target genes, including those encoding cyclins , CDKs , checkpoints regulators, and DNA repair and replication proteins. One of the primary functions of the E2Fs is to control the cell cycle, playing a major role in regulating the G1/S transition. One of the primary regulators of E2F expression is the retinoblastoma gene, RB, a chromatin associated protein that, in its unphosphorylated state, binds to and negatively regulates E2F; hyperphosphorylation of RB releases E2F, allowing cell cycle progression. Many tumor cells have mutant or dysfunctional RB, allowing the aberrant overexpression of the E2Fs and tumor cell proliferation; this aberrant overexpression is better tolerated when p53 is mutated, suppressing subsequent apoptosis. Overexpression of E2F, particularly E2F1, has thus been an attractive target for therapeutic intervention. However, this approach has not yet been successful, most likely due to the redundancy of the E2Fs and the lack of biomarkers for sensitivity. Methods: Using phage display, we have previously identified a novel peptide that, when coupled with penetratin (PEP) to enhance uptake), targets the E2F consensus site in E2F1,2 and 3a, leading to the downregulation of the activating E2Fs and their downstream targets. We have recently enhanced the stability and potency of this peptide by substituting L-Arg within the peptide with D-Arg. Results: Castrate resistant prostate cancer (CRPC) cells, DU-145, lack functional RB, have mutant p53, and are more sensitive to the D-Arg PEP than LnCap or PC-3 cells, with functional RB. Xenograft studies in mice show that the PEP, when encapsulated in PEGylated liposomes (PL-D-Arg PEP) , regresses DU-145 tumors without toxicity. Current studies are examining the combination of the (PL-D-Arg PEP) with taxotere, cisplatin and irradiation in prostate cancer xenografts and organoids from patients. Conclusions: A peptide that inhibits transcription of the activating E2Fs has promise to treat CRPC.

scholarly journals Bone-Targeted Therapies in Metastatic Castration-Resistant Prostate Cancer: Evolving Paradigms

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Joelle El-Amm ◽  
Ashley Freeman ◽  
Nihar Patel ◽  
Jeanny B. Aragon-Ching
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Kinase Inhibitors ◽  
Targeted Agents ◽  
Pain Palliation ◽  
Castration Resistant Prostate Cancer ◽  
Humanized Monoclonal Antibody ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Overall Survival Benefit

Majority of patients with metastatic castrate resistant prostate cancer (mCRPC) develop bone metastases which results in significant morbidity and mortality as a result of skeletal-related events (SREs). Several bone-targeted agents are either in clinical use or in development for prevention of SREs. Bisphosphonates were the first class of drugs investigated for prevention of SREs and zoledronic acid is the only bisphosphonate that is FDA-approved for this indication. Another bone-targeted agent is denosumab which is a fully humanized monoclonal antibody that binds to the RANK-L thereby inhibiting RANK-L mediated bone resorption. While several radiopharmaceuticals were approved for pain palliation in mCRPC including strontium and samarium, alpharadin is the first radiopharmaceutical to show significant overall survival benefit. Contemporary therapeutic options including enzalutamide and abiraterone have effects on pain palliation and SREs as well. Other novel bone-targeted agents are currently in development, including the receptor tyrosine kinase inhibitors cabozantinib and dasatinib. Emerging therapeutics in mCRPC has resulted in great strides in preventing one of the most significant sources of complications of bone metastases.

Docetaxel and imatinib every 21 days for castration resistant prostate cancer: A phase II trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16086-e16086
Author(s):  
T. L. Gillison ◽  
L. J. Appleman ◽  
D. M. Friedland ◽  
T. L. Evans ◽  
P. N. Lara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Castration Resistant Prostate Cancer ◽  
Meaningful Improvement ◽  
Neutropenic Sepsis ◽  
Significant Toxicity ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

e16086 Background: Docetaxel (D) IV every 21 days, is the only cytotoxic agent that prolongs survival in men with castrate resistant prostate cancer (CRPC). Imatinib (I), a tyrosine kinase inhibitor, modulates PDGFR-ß in tumor vasculature. Based on phase I data from our institution, we hypothesized that D plus I would prolong time to progression (TTP) in patients (pts) with CRPC. Methods: Subjects with CRPC received D 60 mg/m2 IV every 21 days plus I 400 mg PO daily. After 10 pts, the study treatment was modified due to toxicity so that pts received I 400 mg on 10 of 21 days/cycle. The primary endpoint was TTP. Secondary endpoints were rate of PSA response and overall survival (OS). The sample size of 43 pts was designed to provide 90% power to detect an increase in TTP from 5 to 8 months. Results: 43 pts enrolled from 8/05 to 9/08. Age at enrollment ranged from 54–86 years (median 69 years). 14 pts received <1 cycle of D plus I and were unevaluable: 10 had significant toxicity, 4 due to non-treatment related reasons. Primary toxicities were hematologic: 21% G4 neutropenia, 5% G4 anemia, and no G4 thrombocytopenia. Fatigue, nausea, diarrhea, and electrolyte abnormalities were common, but <2 cases each of G3-G4 toxicity occurred. 1 case of G5 non-neutropenic sepsis occurred. 29 pts received >2 cycles of chemotherapy (mean 4.6). 12 pts had PR (41.4%), 9 had SD (31.0%), and 8 had no response (27.6%) by PSA. No objective responses were seen by CT imaging among 10 pts with measurable disease. 3 pts remain on trial. For evaluable pts, overall median TTP was 6.4 months (95% CL: 4.8, 8.4 months) compared with TTP of 5 months seen in previous trials. 23 (79%) pts had PSA progression, 3 pts died before progression, and 3 pts remain on trial. For all evaluable pts who had PR or SD by PSA (N = 21), median TTP was 7.1 months (95% CL: 5.5, 9.1 months). Median OS was 23.1 months (95% CL: 11.61 months, NR), compared with 18.9 months for GC Conclusions: Docetaxel on day 1 plus imatinib 10 days of each 21-day cycle resulted in meaningful improvement in TTP in the subset of pts who showed a response. Toxicity precludes its use in the general population, although its role in select pts with good performance status needs to be explored. [Table: see text]

scholarly journals Metastatic Castration-Resistant Prostate Cancer: Critical Review of Enzalutamide

2013 ◽  
Vol 7 ◽  
pp. CMO.S11670 ◽  
Author(s):  
Joelle El-Amm ◽  
Nihar Patel ◽  
Ashley Freeman ◽  
Jeanny B. Aragon-Ching
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Survival Benefit ◽  
First Generation ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Overall Survival Benefit

Enzalutamide, previously known as MDV300, is an oral, second-generation androgen receptor (AR) signaling inhibitor or antagonist that was approved by the Food and Drug Administration in 2012 for the treatment of metastatic castrate-resistant prostate cancer (mCRPC) postdocetaxel. Preclinical studies have demonstrated impressive affinity to the AR compared to the first-generation AR inhibitors. The landmark Phase III AFFIRM trial demonstrated improved overall survival benefit compared to placebo in addition to improvement in all tested parameters. Enzalutamide is currently being studied in several trials prechemotherapy and in earlier settings of prostate cancer. This review will discuss the mechanism of action of enzalutamide, its pharmacokinetics, the preclinical and clinical trials that led to its approval, the ongoing clinical trials, its safety and efficacy, as well as patterns of resistance, and discusses its place in therapy within the context of several recently approved agents for mCRPC.

scholarly journals Impact of Non-Persistence on Healthcare Resource Utilization and Costs in Patients With Immune-Mediated Rheumatic Diseases Initiating Subcutaneous TNF-Alpha Inhibitors: A Before-and-After Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Nuria Carballo ◽  
Enric Garcia-Alzórriz ◽  
Olivia Ferrández ◽  
María Eugenia Navarrete-Rouco ◽  
Xavier Durán-Jordà ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Resource Utilization ◽  
Rheumatic Diseases ◽  
Laboratory Testing ◽  
Healthcare Resource ◽  
Certolizumab Pegol ◽  
Healthcare Resource Utilization ◽  
Immune Mediated ◽  
Before And After ◽  
The Impact

Rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis are chronic progressive immune-mediated rheumatic diseases (IMRD) that can cause a progressive disability and joint deformation and thus can impact in healthcare resource utilization (HCRU) and costs. The main outcome of the study was to assess the effect of non-persistence to treatment with subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) on HCRU costs in naïve patients with IMRD who started treatment with adalimumab, etanercept, golimumab or certolizumab pegol during 12 months after initiation of treatment. The impact of persistence and non-persistence of SC-TNFis on HCRU costs was compared between 12 months before and 12 months after initiating SC-TNFis. Persistence was defined as the duration of time from initiation to discontinuation of therapy. The study was conducted in an acute care teaching hospital in Barcelona, Spain. Data for the period between 2015 and 2018 were extracted from the hospital cost management control database. HCRU costs comprised outpatient care, outpatient specialized rheumatology care, in-patient care, emergency care, laboratory testing and other non-biological therapies. The study population included 110 naïve SC-TNFis patients, divided into the cohorts of persistent (n = 85) and non-persistent (n = 25) patients. Fifty-six percent of patients were women, with a mean (standard deviation) age of 47.6 (14.8) years. Baseline clinical features and HCRU costs over the 12 months before the index prescription were similar in the two study groups. Before-and-after differences in mean (standard deviation) HCRU costs were significantly higher in the non-persistence group as compared to the persistence group for outpatient rheumatology care (€110.90 [234.56] vs. €20.80 [129.59], p = 0.023), laboratory testing (−€193.99 [195.88] vs. −€241.3 [217.88], p = 0.025), other non-biological drugs (€3849.03 [4046.14] vs. −€10.90 [157.42], p &lt; 0.001) and total costs (€3268.90 [4821.55] vs. −€334.67 (905.44), p &lt; 0.001). Treatment persistence with SC-TNFis may be associated with HCRU cost savings in naïve IMRD patients. Prescribing SC-TNFis with the best long-term persistence is beneficial.

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