bluuebunny/crossref_metadata_2025_split huggingface dataset:
Questionnaire to evaluate prostate cancer multidisciplinary committees in Spain.
Authors: Cassinello Javier , Henríquez López Iván , Gonzalez del Alba Aranzazu , González San Segundo Carmen , López Torrecilla José , Gallardo Díaz Enrique , Rodríguez Antolín Alfredo , Juárez Álvaro , Unda Miguel , Arranz Arija Jose Angel 
Published: March 2017

e568 Background: Prostate Cancer (PC) management through Multidisciplinary Committees (MDC) has demonstrated some benefits that could be relevant in patient's outcomes. In Spain MDC are widely implemented although they are not homogeneous among hospitals. The aim of the study was to design a questionnaire to evaluate the functionality/effectiveness of PC MDC in Spain. Methods: The questionnaire was developed from a literature review (22 articles included) and validated by 9 opinion leaders (3 medical oncologists, 3 urologists and 3 radiation oncologists). Experts scored each questionnaire item regarding its ability to assess MDC functionality/effectiveness to obtain a final score of each hospital (from 0-minimum to 100-best functionality/effectiveness) used to classify them according to the cluster analysis (high/intermediate/low level of functionality/effectiveness). The questionnaire was distributed to different specialties by the Spanish Societies of Urological Cancer (URONCOR, GUO and SOGUG). Results: 218 physicians answered the questionnaire, 90 medical oncologists, 86 urologists and 42 radiation oncologists, from 109 hospitals with national representativeness. 91% of hospitals had a Urological MDC, 5% a PC MDC and 4% a General Tumour Committee. Core medical specialities (Urology, Medical Oncology, Radiation Oncology, Pathology, Radiology) were represented in > 80% of MDC. Only 9% MDC discussed the treatment of all patients with PC whereas in 60% of MDC less than 50% of the whole population of PC patients were evaluated. According to 95% of physicians, agreement in therapeutic strategies were reached in > 80% of cases discussed. A score was established that allowed the classification of MDC in each center according to its functionality into 3 clusters: 43% of centers fell in cluster 3 (high), 36% in cluster 2 (intermediate) and 21% in cluster 1 (low). Conclusions: Urological Cancer MDC is a widespread practice in Spain, which comprises a wide range of medical specialists that meet regularly to agree on therapeutic strategies for PC patients. Less than 50% of total PC patients are evaluated in Urological MDC. It is still necessary to improve some aspects allowing more hospitals to reach a higher level of functionality.
Impact of pharmacist-led monitoring of olaparib (O) for metastatic castrate resistant prostate cancer (mCRPC).
Authors: McNatty Andrea , Dow Elizabeth , Bryce Alan Haruo 
Published: March 2017

e569 Background: O is a PARP inhibitor that has received breakthrough designation for use in mCRPC based on a study in which a subset of 16 patients with DNA repair defects had an 80% response rate. O is an oral tablet taken twice daily. Studies have demonstrated that compliance with oral agents is often poor, and the less frequent contact with medical staff increases the risk of toxicities when compared to IV therapies. This is compounded by a bias where oral medications are thought of as less toxic than IV medications. The toxicities of O include myelosuppression, nausea, vomiting, and fatigue. Our practice employs a pharmacist to conduct weekly phone calls for toxicity management, monitor patient adherence, and monitor for drug-drug interactions. We report our experience with patient adherence, toxicities, and response with O in mCRPC. Methods: A single institution, retrospective review was performed on 14 mCRPC patients treated with O from November 2015 - October 2016. Adherence and toxicity data were assessed and documented via phone calls conducted by a clinical pharmacist. The primary outcomes were number of missed doses, incidence of toxicities, and dose modifications. The secondary outcome was response rate, defined as a 50% reduction in PSA or radiographic response according to RECIST 1.1 for a duration of greater than 3 months. Results: Patients reported taking 99% of the prescribed doses. The toxicities observed most commonly were fatigue (64%), nausea (57%) and anemia (57%). As a result of toxicities, four patients required a dose reduction to 300 mg BID, three patients required a dose reduction to 200 mg BID and two patients were initiated on 200 mg BID and maintained on that dose until progression. Partial responses were seen in 6 of 14 patients. Conclusions: Our pharmacist led adherence program facilitated timely dose adjustments and high patient adherence. Response rates were comparable to published data.
Overall survival beyond first-line docetaxel in patients with metastatic castrate-resistant prostate cancer treated with abiraterone acetate or enzalutamide.
Authors: Heo Mi Hwa , Park Se Hoon , Kim Hee Kyung , Cho Jinhyun , Kim Youjin , Lee Hansang 
Published: March 2017

e570 Background: In post-docetaxel setting of metastatic castrate-resistant prostate cancer (mCRPC), survival benefit with abiraterone acetate or enzalutamide is well established. This retrospective study was performed with the data obtained our cancer chemotherapy registry to evaluate real-world mCRPC patient outcomes. Methods: All consecutive patients treated with either abiraterone acetate or enzalutamide in post-docetaxel setting between 2013 and 2014 were included. The decision for administering second-line agents was, in most cases, at the discretion of the treating oncologists. The primary endpoint of this study was overall survival (OS), and the secondary endpoints included safety, prostate-specific antigen (PSA) response ( ≥ 50% decline) and progression-free survival (PFS). Univariate and multivariate analyses for OS were performed on the recognized baseline parameters and therapy. Results: A total of 54 eligible mCRPC patients received either abiraterone acetate (n = 25) or enzalutamide (n = 29). At the time of commencing second-line therapy, the patients’ median age was 70 years (range, 45-86) and 30 patients (56%) had a symptomatic disease. Visceral disease was present in 12 patients, and 12 had bone-only metastasis. Both were well-tolerated without significant toxicities. PSA response was observed in 36% and 52% for abiraterone acetate and enzalutamide, respectively. The estimated median PFS and OS were 5 and 15 months, respectively. Multivariate analysis revealed that the presence of clinical symptoms was the only independent prognostic factor for OS. Conclusions: Within the limitation of small sample size, the results are consistent with existing literature suggesting that both abiraterone acetate and enzalutamide appear to be effective as second-line therapy for docetaxel-pretreated mCRPC.
Heterogeneous populations driven by clinical practice: A case example comparing enzalutamide (ENZA) and bicalutamide (BIC).
Authors: Kim Ruth , Brookhart M. Alan , Flanders Scott , Schultz Neil M. , Fryzek Jon , Barlev Arie 
Published: March 2017

e571 Background: Comparative real-world insurance claims data (RWD) analysis can be used to compare homogeneous cohorts (to avoid selection bias). Since the National Comprehensive Cancer Network guidelines recommend ENZA for metastatic castration-resistant prostate cancer (PC) and BIC for localized PC, it was of interest to evaluate these 2 heterogeneous cohorts as the ENZA cohort, being further advanced in the disease, has a worse prognosis than the BIC cohort. Here, we describe the results of a post hoc analysis on the ENZA and BIC cohorts to confirm the heterogeneity of demographics presented in a published study (Behl A et al. J Clin Oncol. 2016;34:235). Methods: The RWD captured enrollees with PC, claims for ENZA or BIC from 09/01/2012–12/31/2014, and at least 6 mo of continuous enrollment prior to the index date. After replicating methods from Behl et al using Truvan, we explored the balance of demographics in baseline periods greater than 6 mo. Differences in demographics and the post hoc analysis were compared. Results: Behl et al reported balanced age between the ENZA (73.1±10.0 y) and BIC (71.4±10.5 y) cohorts. However, 90% (531/592) of the ENZA cohort were metastatic vs 35% (1917/5524) of the BIC cohort. The Quan-Charlson comorbidity index was higher for the ENZA (5.6±2.1 y) than BIC (3.2±2.1 y) cohort. In the ENZA cohort, abiraterone acetate (ABI) or BIC utilization in the baseline period was higher (53%) than in the BIC cohort (0%). When the baseline period was greater than 6 mo, per our post hoc analysis, prior use of ABI or BIC increased to 68% for the ENZA cohort and remained unchanged in the BIC cohort. Conclusions: Despite results from the Behl analysis, the ENZA and BIC cohorts were dissimilar; ENZA patients had more advanced disease (metastatic disease; received ≥ 1 therapy) than BIC patients. Comparison of such heterogeneous populations can lead to biased estimates of treatment effects. Analyses lacking appropriate measures of prognostic variables that guide treatment decisions should be cautiously interpreted. Further analysis is required to identify best practices for using RWD and to address confounding driven by clinical practice.
Early assessment of PSA response in patients with mCRPC treated with enzalutamide and abiraterone.
Authors: Feibus Allison H. , Guccione Jeffrey R. , Vasudevamurthy Ashwin , Ledet Elisa M. , Cotogno Patrick , Manogue Charlotte , Ernst Emma M. , Lewis Brian E. , Silberstein Jonathan L. , Sartor A. Oliver 
Published: March 2017

e574 Background: Abiraterone (Abi) and enzaleutamide (Enza) are first-line agents for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Primary resistance is well-documented, but little data exists for rapid treatment responders. This study intended to further characterize patients with early prostate-specific antigen (PSA) decline. Methods: A single-institution retrospective review was performed on 123 mCRPC patients treated with Abi and/or Enza. PSA was recorded every 4 weeks for the duration of treatment. The primary endpoint was to describe PSA response, including sensitivities and specificities, as a predictor of later treatment response (defined as ≥50% decrease in PSA from baseline). Additional clinical covariates were also evaluated as treatment-response predictors. Results: A PSA response to Abi was achieved in 52/123 (42%) of patients. Median time to PSA nadir was 37 days. 30/52 (58%) patients responded to the drug within 4 weeks. Median length of time on drug was 110 days. A PSA response to Enza was achieved in 21/123 (17%) of patients. Median time to PSA nadir was 140 days. 18/21 (86%) of patients responded to the drug within 4 weeks. Median length of time on drug was 161 days. Conclusions: Percentage of PSA decline and time to drug response for Enza and Abi are important variables that can serve as reliable way for clinicians to predict long-term PSA response. It is vital to make appropriate treatment modifications for patients that do not display early PSA response. [Table: see text]
Association between primary surgery and all-cause mortality among elderly patients with high-risk prostate cancer.
Authors: Chhatre Sumedha , Lee David Inkoo , Yu Doyeong , Malkowicz S. Bruce , Jayadevappa Ravishankar 
Published: March 2017

e576 Background: To determine the five year survival impact of primary surgery compared to radiation therapy in older men with high risk prostate cancer. Methods: This was a population-based cohort study using Surveillance, Epidemiology, and End Results (SEER)-Medicare patients 66 years or older, diagnosed for prostate cancer between 2004 and 2008. High-risk prostate cancer was identified as Gleason score of ≥ 8, or clinical stage T3a. Treatments studied were definitive local (curative intent) therapy (surgery or radiation therapy) within 180 days of prostate cancer diagnosis. The two treatment groups were retrospectively followed for one-year pre and five years post diagnosis. Main outcome measure was five-year all-cause mortality and cancer specific mortality. Sequential Cox regression was used to assess the hazard of mortality associated with surgery, compared to radiation therapy, after adjusting for socio-demographic variables, variables and propensity score. Results: We identified a cohort of 24,838 men newly diagnosed for high-risk for prostate cancer between 2004 and 2008. Forty-seven percent of these had surgery (n = 11,696) as well as radiation therapy (n = 11,724) as a primary treatment with curative intent within 180 days of diagnosis. Mean age at diagnosis of radiation therapy group was higher compared to surgery group (73.5, sd = 5.3 vs. 70.3, sd = 4.9; p = 0.020). Radiation group had higher comorbidity compared to surgery group (37% vs. 26%, p = 0.0316). Unadjusted all-cause mortality comparison over five years of follow-up showed that surgery treatment was associated with lower mortality (HR = 0.58, CI = 0.54, 0.62). After adjusting for propensity score, the hazard of all-cause five year mortality remained lower for surgery compared to radiation therapy (HR = 0.86, CI = 0.78, 9.4). Conclusions: Over a five-year follow-up, primary surgery was associated with improved survival compared to radiation therapy in high-risk prostate cancer patients. Longer follow-up is needed to determine if the survival advantage of surgery will persist as well as factors contributing to the difference in survival.
Interim analysis of NCT02458716: Feasibility of cytoreductive prostatectomy in men newly diagnosed with metastatic prostate cancer.
Authors: Yuh Bertram E. , Kwon Young Suk , Shinder Brian , Kim Sinae , Lee Nara , Ruel Nora , Kim Isaac Yi 
Published: March 2017

e578 Background: Emerging evidence has suggested that local tumor control may enhance the effect of subsequent therapies in patients with metastatic prostate cancer. However, little is known about surgical safety of cytoreductive prostatectomy (CRP). In this study, we report the first interim analysis of a phase I study evaluating the safety and feasibility of CRP. Methods: The study was approved by the IRB and activated in June, 2015. Individuals with newly diagnosed clinical metastatic prostate cancer to lymph node or bones (cT1-3N1M0 or cT1-3N0M1a-b) were recruited. Following surgery, all patients received androgen deprivation therapy. The primary endpoint is the major complication rate (Clavien ≥ III). The secondary outcome measures are the time to PSA nadir and rate of incontinence (pad-free). Results: A total of 20 men from two institutions have been enrolled and undergone CRP. Overall, 6 (35.3%) perioperative complications were observed, including 1 major complication (Clavien ≥ III). There were 5 minor complications, including deep venous thrombus (Clavien II), postoperative ileus (Clavien II), and 3 cases of urethral anastomotic leaks (Clavien I). In men with a minimum of 6 month follow-up, PSA < 0.2 ng/ml in 63.6% of men and 50% of men were pad free. Conclusions: CRP is surgically feasible in carefully selected patients. However, early incontinence rate is high. Further studies are warranted to further define long-term complications and verify the oncologic benefits of the surgery. Clinical trial information: NCT02458716. [Table: see text]
Antitumor activity of abiraterone, enzalutamide, and docetaxel following treatment with diethystilbestrol in castration-resistant prostate cancer.
Authors: Assoun Sandra , Campedel Luca , Roupret Morgan , Vaessen Christophe , Parra Jerome , Boostandoost Haide Angele , Comperat Eva , Simon Jean-Marc , Khayat David , Bitker Marc-Olivier , Malouf Gabriel G. , Spano Jean-PHilippe 
Published: March 2017

e581 Background: Docetaxel and Next-Generation Anti-Androgens (NGAA) including abiraterone and enzalutamide represent the standard of treatment for patients with castration-resistant prostate cancer (CRPC). Treatment sequencing of these agents is a challenge. Recent studies identified cross-resistances between hormonal therapies and taxanes, as well as between different NGAA. In aiming to elucidate whether synthetic oestrogen diethylstilbestrol (DES) therapy impacts the efficacy of later-line treatments or not, we evaluated the antitumor activity of NGAA and docetaxel following DES therapy in CRPC patients. Methods: All patients with CRPC treated at Pitié-Salpêtrière hospital in first-line setting with DES from September 1995 to July 2016 were retrospectively identified. We evaluated further activities of abiraterone, enzalutamide and docetaxel in those patients after DES therapy, using Prostate Cancer Working Group 3 criteria. Clinicopathologic characteristics, including age, performans status, metastatic sites at diagnosis and treatments initiation, and data survival were also assessed. Results: Twenty-three patients with CRPC were initially treated with DES with a median time to prostate-specific antigen (PSA) progression of 9.7 months (range, 4.7-20.3). Thirteen patients(56.5%) received abiraterone or enzalutamide before docetaxel and 21 patients (91.3%) after. Median age at first NGAA initiation was 79 years) range, 55-91). Only one patient (7.7%) achieved a PSA decline before docetaxel and two out of 18 evaluable patients (11.1%) after docetaxel. Median time to PSA progression and overall survival with a NGAA treatment were respectively 2.8 (range, 2.0-4.1) and 16.5 months(range, 4.3-31.0). Fifty percent of patients showed a PSA response with docetaxel. No clinical factors were found to be significantly associated with PSA response to NGAA treatment, nor to docetaxel. Conclusions: The activity of NGAA appears markedly limited after a DES therapy, regardless of the PSA response to docetaxel. These data suggest the likelihood of a cross-resistance mechanism between DES and NGAA, without no impact on taxanes pathways.
Head-to-head pharmacokinetic and pharmacodynamic comparison of subcutaneous versus intramuscular leuprorelin acetate formulations in male patients.
Authors: Moul Judd W. , McLane John A. , Atkinson Stuart , Concepcion Raoul S. 
Published: March 2017

e589 Background: Leuprolide acetate (LA) is the standard-of-care luteinizing hormone-releasing hormone (LHRH) agonist used to suppress serum testosterone (T) in the treatment of advanced prostate cancer. There are currently two LA formulations available: a controlled-release implant injected subcutaneously (SC) or a microsphere intra-muscular (IM) injection. The study compared the pharmacokinetics/pharmacodynamics of both formulations at the same one-month dose. Methods: Thirty-two healthy men were randomized to receive a single 7.5 mg injection of SC-LA (n = 16) or IM-LA (n = 16) in this phase 1, open-label, parallel-group study. Serum LA, T, and luteinizing hormone (LH) were assessed. Results: The initial surge of LA was higher for IM-LA than SC-LA (Cmax 27±4.9 vs. 19±8.0 ng/mL, respectively), with a shorter tmax (1.0±0.4 vs. 2.1±0.8 hrs). Mean serum LA remained above the level of quantification (LOQ, 50 pg/mL) through Day 49 for SC-LA, whereas for IM-LA, mean serum LA dropped below the LOQ after Day 28. Median LH concentration remained low at Day 56 in the SC-LA group, whereas LH levels began to rise after Day 35 in the IM-LA group. Consequently, serum T began to increase by Day 42 in the IM-LA group. By Day 56, 13 SC-LA subjects maintained serum T levels ≤ 50 ng/dL vs. 0 in the IM-LA group. Both SC-LA and IM-LA were well tolerated, however SC-LA subjects experienced more mild injection site disorders compared to IM-LA. Conclusions: The initial surge of LA was higher for IM-LA than SC-LA (Cmax 27±4.9 vs. 19±8.0 ng/mL, respectively), with a shorter tmax (1.0±0.4 vs. 2.1±0.8 hrs). Mean serum LA remained above the level of quantification (LOQ, 50 pg/mL) through Day 49 for SC-LA, whereas for IM-LA, mean serum LA dropped below the LOQ after Day 28. Median LH concentration remained low at Day 56 in the SC-LA group, whereas LH levels began to rise after Day 35 in the IM-LA group. Consequently, serum T began to increase by Day 42 in the IM-LA group. By Day 56, 13 SC-LA subjects maintained serum T levels ≤ 50 ng/dL vs. 0 in the IM-LA group. Both SC-LA and IM-LA were well tolerated, however SC-LA subjects experienced more mild injection site disorders compared to IM-LA.
Polymer delivered, subcutaneously administered leuprolide acetate provides stable and long-term drug delivery and testosterone suppression in 4 pivotal trials.
Authors: Chu Franklin , Atkinson Stuart , McLane John A. , Kassabian Vahan 
Published: March 2017

e592 Background: Prostate cancer patients receive androgen deprivation therapy (ADT) to suppress testosterone (T) to prevent proliferation of cancer cells. T suppression levels achieved by bilateral orchiectomy remain the gold standard for the target of suppression by ADT. Although the historical threshold definition of castration is T ≤ 50 ng/dL, increasing evidence suggests T lower than 20ng/dL may improve clinical outcomes, e.g., an increased cancer specific survival and delayed disease progression. To determine the minimal threshold of serum leuprolide required to maintain castrate level T suppression in prostate cancer patients, data from 4 pivotal trials evaluating long-acting, subcutaneously (SC) administered leuprolide acetate (LA) formulated with a biodegradable polymer were pooled. Methods: 438 eugonadal prostate cancer patients (age 40-86) were treated with SC-LA at 7.5, 22.5, 30, or 45mg delivered with a single dose lasting over 1, 3, 4, or 6 months (n = 120, 117, 90, 111), respectively in 4 open-label, fixed-dose, pivotal trials. Descriptive statistics were used to summarize the median concentration of leuprolide acetate at each time point as well as to determine level of T suppression. Results: Over the dosing intervals of the 1, 3, 4 and 6-month SC-LA formulations, median serum leuprolide levels were consistent and median serum T remained below T < 20 ng/dL. In the pooled analysis (n = 86), 99% of patients with LA ≥ 0.1 ng/mL after injection achieved castration after 4 Weeks. Conclusions: These data suggest that SC-LA achieves consistent and prolonged drug delivery resulting in sufficient serum LA levels to provide favorable T suppression below 20 ng/dL, which may have clinical outcomes, e.g., increased cancer specific and progression free survival.