bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II clinical study of radium-223 chloride (BAY 88-8223) in Japanese patients with symptomatic castration-resistant prostate cancer (CRPC) with bone metastases.
Authors: Uemura Hiroji , Nagamori Satoshi , Wakumoto Yoshiaki , Uemura Hirotsugu , Kimura Go , Yokomizo Akira , Kikukawa Hiroaki , Mizokami Atsushi , Kosaka Takeo , Masumori Naoya , Kawasaki Yoshihide , Yonese Junji , Nasu Yasutomo , Fukasawa Satoshi , Sugiyama Takayuki , Uemura Motohide , Yamaguchi Iku , Tsutsui Hirokazu , Matsunaga Eisuke , Matsubara Nobuaki 
Published: February 2017

167 Background: The ALSYMPCA study was conducted to evaluate the alpha-emitting radiopharmaceutical Radium-223 Chloride (BAY 88-8223) in patients with symptomatic bone metastases in Castration resistant prostate cancer (CRPC). This trial met its primary endpoint of overall survival at the time of pre-planned interim analysis. Post hoc analysis showed a reduction from baseline in total ALP at 12 weeks (32% reduction in the BAY 88-8223 arm vs. 37% increase in placebo arm, P < 0.001) (Sartor et al. ASCO 2013). We are reporting here a single-arm, open-label, multicenter, phase II clinical study of BAY 88-8223 in Japanese patients with symptomatic CRPC with bone metastases. Methods: Eligible patients had progressive, symptomatic CRPC with at least 2 bone metastases on bone scintigraphy and no known visceral metastases; were receiving Best Standard of Care; and either had previously received docetaxel, were docetaxel ineligible, or had refused docetaxel. Patients received 6 injections of radium-223 (50 kBq/kg IV) every 4 weeks. The primary endpoint was percentage of change in total ALP from baseline at 12 weeks. Secondary endpoints included overall survival, time to symptomatic skeletal event, percentage of change in bone ALP/PSA/biomarkers, and safety. Results: A total of 67 subjects were enrolled; 18 were screening failures, and 49 were received to the study treatment and received at least one administration from September 2013 to May 2014. The mean percent change in total ALP from baseline at 12 weeks was -19.3% (95%CI: -28.0% to -10.7%). The results of secondary endpoints will be presented. The safety and tolerability profile for BAY 88-8223 were highly favorable and only 1 subject (2.0%) experienced lymphocyte count decreased as a Grade 4 adverse event, and there was no death during the study treatment and within 30 days after the last injection of study treatment. Conclusions: The reduction from baseline in total ALP at 12 weeks seen in this phase II study is consistent with the results shown in ALSYMPCA study. Overall, BAY 88-8223 was well tolerated in Japanese patients with CRPC and bone metastases. Clinical trial information: NCT01929655.
Gleason score and the risk of cause-specific and overall mortality following radiation with or without 6 months of androgen deprivation therapy for men with unfavorable-risk prostate cancer.
Authors: Warren Laura Elizabeth , Chen Ming-Hui , Denham James William , Steigler Allison , Renshaw Andrew A. , Loffredo Marian J. , Kantoff Philip W. , D'Amico Anthony V. 
Published: February 2017

171 Background: We evaluated whether a differential impact of adding 6 months of androgen deprivation (ADT) to radiation therapy (RT) on all-cause, prostate cancer-specific, and other-cause mortality (ACM, PCSM, OCM) in men with unfavorable-risk PC exists within Gleason score (GS) subgroups. Methods: Individual patient data from 743 men with unfavorable-risk PC from two randomized ADT trials were utilized. Competing risks and Cox regression were used to determine whether adding 6 months of ADT to RT significantly impacted PCSM, OCM and ACM within GS subgroups. Results: Men with GS 9,10 versus ≤ 8 were significantly more likely to be over 75 (23.3% versus 12.7%;p = 0.03). At a median follow-up of 11.9 and 11.8 years in the 683 and 60 patients with GS ≤ 8 and GS 9,10, 315 (46.1%) and 44 had died (73.1%), respectively. ADT in men with GS ≤ 8 was associated with significantly decreased ACM (Adjusted hazard ratio (AHR) 0.66; 95% confidence interval (CI): 0.52-0.82; p < 0.001) and PCSM (0.43; 0.28-0.66; p < 0.001) but was not associated with OCM (0.90; 0.68-1.17; p = 0.43). Among men with GS 9,10 PC, ADT significantly reduced PCSM (0.33; 0.11-0.99; p = 0.048) but not ACM (0.79; 0.38-1.61; p = 0.51) and increased OCM (2.16; 0.81-5.79; p = 0.12) resulting in opposite effects of ADT on OCM by GS subgroup (Table) such that the relative AHR of OCM in GS 9,10 versus ≤ 8 was nearly significantly increased (2.42; 0.87-6.71; p = 0.09). Conclusions: While ADT reduced PCSM for all men, survival was not prolonged in men with GS 9,10 due to ADT-driven increased OCM. This supports the hypothesis that older men with significant comorbidity may not experience prolonged survival when ADT is added to RT. [Table: see text]
OLIGOPELVIS – GETUG P07, a multicentre phase II trial of combined salvage radiotherapy and hormone therapy in oligometastatic pelvic node relapses of prostate cancer: Preplanned analysis of acute toxicity.
Authors: Supiot Stephane , Crehange Gilles , Buthaud Xavier , Pasquier David , Hasbini Ali , De Laroche Guy , Pommier Pascal , Loos Genevieve , Beckendorf Veronique , Sargos Paul , Rio Emmanuel , Campion Loic 
Published: February 2017

173 Background: We explored the role of salvage pelvic radiotherapy combined with LH-RH agonists in pelvic oligometastatic patients (pts) detected by 18F-choline positron-emission tomography (FCH-PET) imaging in biochemically relapsing prostate cancer patients following radical therapy. We report a preplanned analysis of acute toxicity and quality of life after the first 20 pts. Methods: Biochemically relapsing prostate cancer pts with 1-5 FCH-PET positive oligometastatic pelvic lymph nodes received high-dose image-guided intensity-modulated radiation therapy (RT: pelvic lymph nodes 54 Gy, 30 f; FCH-PET-positive lymph nodes 66 Gy, 30 f; prostate bed 66 Gy, 33 f; if FCH-PET-positive prostate bed relapse 72 Gy, 36 f) combined with 6 months LH-RH agonists. Primary objective was biochemical-clinical failure-free survival. After the first 20 pts, a preplanned analysis of toxicity at 1 months after RT completion was conducted. Stopping criteria were more than 10 or 2 pts experiencing grade 2 or 3 toxicity respectively. Changes in toxicity (NCI-CTC AE v4), and quality of life (EORTC QLQ-C30 and PR25 questionnaires) over time were analyzed by the Wilcoxon signed-rank test. Results: 20 pts (median age 62) presenting oligometastatic pelvic lymph nodes (mean 1.7) received RT to lymph nodes in all pts and to the prostate bed in 8 pts with a boost to a local relapse in 2 pts. Grade 2 gastrointestinal and genitourinary toxicity was noted in 4/20 and 0/20 pts respectively during radiotherapy that resolved completely in all pts one month after treatment. No grade 3 toxicity was noted. At 1 month, significant worsening was reported by pts for 4/21 QoL items but the worsening was clinically relevant ( > 10 points) for 2 items only: fatigue and dyspnea. However, there was significant - but clinically non-relevant ( < 10 points) - worsening of physical functioning and hormonal-treatment related symptoms. Conclusions: High-dose RT to the pelvis and oligometastatic lymph nodes did not increase acute toxicity. As per protocol, the study resumed and is now recruiting 50 more patients. Clinical trial information: NCT02274779.
Dynamic correlation of serum C-reactive protein (CRP) levels with serum prostate-specific antigen (PSA) levels in patients with prostate cancer (PCa) on androgen deprivation therapy (ADT).
Authors: Kucuk Omer , Balci Bengi , Liu Yuan , Zhang Chao , Yilmaz Bahiddin , Atag Elif , Karaoglu Aziz , Jani Ashesh B. , Harris Wayne , Carthon Bradley Curtis , Rossi Peter John , Master Viraj A. , Alemozaffar Mehrdad , Filson Christopher Paul , Sanda Martin George 
Published: February 2017

181 Background: CRP, a marker of inflammation, has been associated with disease extent and prognosis in urologic cancers (Huang J, et al. Mol Aspects Med, 2015). In this study we wanted to see whether CRP is dynamically correlated with PSA in patients with PCa when they were on ADT. Methods: 83 patients on ADT were included in this analysis. Their CRP and PSA were recorded longitudinally and the range of length of follow up time is from 3 to 47 (median 16) months. All patients had at least 3 pairs of CRP and PSA measurements available. Statistical analysis was conducted using Dynamic Correlation (Dubin JA, Muller H-G. J Am Stat Assoc, 2005) package ‘dynCorr’ in R 3.1.2, and SAS Version 9.4. Significance levels were set at 0.05. We calculated dynamical correlation as function of time lag between CRP and PSA measurements along with 95% bootstrap confidence intervals and p value. Results: See below table. Conclusions: We found that at lag = 30 days (CRP leads PSA by 30 days), the correlation is significant at level of < 0.05, which means any increase or decrease of CRP at a given time point will lead to about same change in PSA 30 days later. Though these findings must be verified in a larger setting, our results support, in the setting of ADT use, the role of CRP as an early marker of PCa progression and treatment response. [Table: see text]
Do we need daily corticosteroid combined with docetaxel when treating against castration-resistant prostate cancer?
Authors: Shimomura Tatsuya 
Published: February 2017

184 Background: Depend on the result of TAX 327, docetaxel are usually used with daily corticosteroid (prednisone) against castration resistant prostate cancer (CRPC). However there is no evidence that combination of daily corticosteroid itself with docetaxel improve survival rate. In this study we investigated whether daily corticosteroid have survival benefit in our docetaxel treatment cohort. Methods: Total of 120 CRPC cases were treated with docetaxel in our department between 2011 and 2014. We compared the group 1 (with daily corticosteroid) and group 2 (without daily corticosteroid) and evaluated their clinical outcome. In group 2, there was no case using estramustine or any estrogen medicine. Results: Group 1 was 104 cases and group 2 was 11 cases in this study. In terms of clinical and pathological demographics at diagnosis of prostate cancer and at starting docetaxel, almost all of the factors did not have significant difference between group1 and 2 other than white blood cell count(mean 7142 and 5664, respectively. p = 0.0449). About the treatment outcome, there were no significant difference in overall survival (p = 0.8696) , PSA response rate (39.2% vs 52.0%, p = 0.2348), PSA decline ³a50% (38.4% vs 45.5%,p = 0.651), PSA decline ³a90% (14.4% vs 36.4%, p = 0.062) and number of cycles (Mean 7.19 vs 8.33, p = 0.174) between group 1 and 2. Conclusions: Although this study was retrospective and the cohort was small, we did not find the difference of outcome among the 2 groups. At least, we could say that there was no survival benefit in the daily corticosteroid groups. And there is a possibility that we do not need to combine daily corticosteroid with docetaxel. We will need prospective randomized trial to prove this hypothesis.
Comprehensive genomic profiling of neuroendocrine carcinoma of the prostate.
Authors: Pal Sumanta K. , Milowsky Matthew I. , Elvin Julia Andrea , Ali Siraj Mahamed , Hoffman-Censits Jean H. , Vergilio Jo-Anne , Suh James , Mian Badar , Fisher Hugh A.G. , Nazeer Tipu , Miller Vincent A. , Stephens Philip J. , Ross Jeffrey S. 
Published: February 2017

187 Background: Neuroendocrine carcinoma of the prostate (NCAP) is an aggressive high grade malignancy that often presents as metastatic disease. Current treatments of this tumor have only modest benefit leading investigators to query whether comprehensive genomic profiling (CGP) would have potential to discover novel targets of therapy. Methods: DNA was extracted from 40 microns of FFPE sections from 37 consecutive cases of relapsed/metastatic NCAP. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 583X for up to 315 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. Genomic alterations (GA) included base substitutions (SUB), INDELs, copy number alterations (CNA) and fusions/rearrangements. Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: The median age of the men in this study was 65.1 years (range 43 to 83 years). All (100%) cases were positive for neuroendocrine markers on immunohistochemical staining and were Stage IV at the time of CGP. Samples used for sequencing were obtained from the primary tumor in 9 (24%) of NCAP and from metastatic sites in 28 (76%) of NCAP (12 liver, 6 LN, 2 each from bladder, pelvis and soft tissue, and 1 each from rectum, bone, urethra and ureter. There were 213 total GA (5.8 GA/sample) and 47 CRGA (1.3 CRGA/sample). The most frequent GA were non-CRGA mutations in TP53 (68%) and RB1 (51%). TMPRSS:ERG fusions were identified in 32% of cases whereas AR was altered in 8% (1 mutation and 2 amplifications). The most frequent CRGA involved PTEN (32%), BRCA2 (14%), FGFR1 (5%), PIK3CA (5%) and AKT2 (3%). No alterations in BRAF were identified. Clinical responses to MTOR inhibitors in patients with MTOR pathway alterations will be presented. Conclusions: NCAP has distinctive genomic alterations from classic acinar CAP including reduced frequencies of alterations in TMPRSS:ERG and AR and frequent RB1 mutations. Multiple alterations in the MTOR pathway identified in this infrequent tumor type suggest that these patients may be candidates for MTOR inhibitors and other targeted therapies.
Real-world experience of therapeutic sequencing and time to first anticancer intervention (ACI) following sipuleucel-T (sip-T): Initial data from the PROCEED registry.
Authors: Sartor A. Oliver , Cooperberg Matthew R. , Armstrong Andrew J. , Vogelzang Nicholas J. , Vacirca Jeffrey L. , Scholz Mark C. , Dakhil Shaker R. , Nordquist Luke T. , Heath Elisabeth I. , Chang Nancy N. , LIll Jennifer Susan , Higano Celestia S. 
Published: February 2017

194 Background: Sip-T is an autologous immunotherapy approved for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).Many therapeutic agents have been approved in a short time frame, and their optimal sequencing in mCRPC is under investigation. The sequencing of agents post–sip-T treatment on PROCEED (NCT01306890) and factors associated with a shorter time to first ACI (tACI) are described. Methods: The number of unique and most common sequences and sequence trends were analyzed. Post–sip-T ACIs evaluated were abiraterone (abi), enzalutamide (enz), docetaxel (D), and cabazitaxel (cbz), excluding radium-223 due to its late approval relative to PROCEED initiation. The tACI and factors associated with shorter tACI were assessed. Results: 1902 pts received ≥1 sip-T infusion, and an estimated 37.0% and 21.2%had not received an ACI at 1 and 2 y, respectively, post–sip-T. 1331 (70%) pts received abi, enz, D, or cbz after sip-T. 47 therapy sequences were recorded post–sip-T, with the most used therapies in order of prevalence: abi alone, enz alone, D alone, abi → enz, abi → D, D → enz, and D → abi. The most common post–sip-T sequences beginning with abi, enz, or D are below (Table). Only 25 pts received cbz as the first ACI post–sip-T. Pts who received abi prior to sip-T had a shorter median tACI (4.6 mos) compared with all pts (8.3 mos) or pts with D prior to sip-T (7.3 mos). Higher baseline alkaline phosphatase, lower hemoglobin, and prior radical prostatectomy were associated with shorter tACI. Conclusions: In the evolving mCRPC space, 47 unique ACI sequences were recorded post-sip-T. The most common sequences post–sip-T were abi, enz, and D as single agents. Prior abi was associated with a shorter tACI post–sip-T, which warrants longer follow-up. While many pts received subsequent therapy, ~20% had not received an ACI at 2 y post–sip-T. Clinical trial information: NCT01306890. [Table: see text]
Circulating tumor cell (CTC) detection, N-terminal androgen (AR) characterization, and PTEN loss in metastatic or advanced castration resistant prostate cancer (CRPC).
Authors: Jia Shidong , Baird Sarah , Anderson Amanda K. L. , Werner Shannon L. , Petersen Jane , Huw Ling , Marrinucci Dena C. , Patel Premal H. 
Published: February 2017

195 Background: Detection and characterization of CTCs offers a minimally invasive mechanism for understanding patient response to therapy and disease evolution. Here we describe a proprietary technology platform to examine CTC incidence, N-terminal AR expression, and PTEN loss in metastatic or advanced CRPC patient samples from a phase II clinical trial (GO27983) testing the combination of the AKT inhibitor ipatasertib and abiraterone. Methods: Blood samples from CRPC patients (n = 283) were collected at screening and shipped to Epic Sciences. Upon receipt, the nucleated cells were plated onto microscope slides and stored at -80C. Two slides were thawed per patient and analyzed with an N-terminal AR CTC assay. CTCs were detected using a combination of CD45 exclusion, CK and N-terminal AR expression, and morphologic criteria. Traditional (CD45-, CK+, DAPI+) and Non-Traditional (CD45-/CK- with distinct morphology or CD45-/CK+ with fragmented nuclei) CTCs were enumerated and N-terminal AR expression was quantified for each CTC. Samples with > 2 Traditional CTCs enumerated per slide were further evaluated for PTEN loss by FISH (n = 170). Results: Traditional CTCs were detected ( ≥ 1 cell/ml) in 86% (242 of 283) of samples. Non-traditional CTCs were detected in 93% (263 of 283) of patients. N-terminal AR positivity was detected ( ≥ 1 AR+ cell/ml) in 53% (128 of 242) of Traditional CTC-positive samples, with the % positivity ranging from 0.4-100%. PTEN status was determined for 66% (160 of 243) of patients with Traditional CTCs detected. Patients with homozygous (HO) PTEN loss had a significantly higher mean CTC/mL (p = 0.0013) and AR+ CTC/mL value (p = 0.0014) than patients with PTEN non-deleted status. Conclusions: The ability of the Epic Sciences platform to detect AR+ CTCs and PTEN loss at screening provides a non-invasive approach to characterizing and monitoring CTCs identified in advanced CRPC patients. The study is ongoing to monitor longitudinal changes in CTC incidence and AR expression in relation to PTEN status. Clinical trial information: NCT01485861.
Cardiovascular safety profile of VT-464 in patients (pts) with castrate-resistant prostate cancer (CRPC).
Authors: Kurman Michael R , Sager Philip , Rudoltz Marc S. , Eisner Joel , Goodman Daniel , Heyman Eugene , Salvail Daniel , Bell Caroline , Moore William R. 
Published: February 2017

198 Background: VT-464 is a dual selective inhibitor of CYP17,20 lyase and an androgen receptor antagonist in development for the treatment of CRPC. In early clinical testing, several pts receiving VT-464 in 28-day cycles were noted to have syncopal, pre-syncopal or vaso-vagal episodes with typical prodromes. To further evaluate these events, Holter monitoring (HM) was performed in pts enrolled in two clinical studies. Methods: Continuous HM was performed at Screening, after the first dose of VT-464 C1D8, and C2D1 for study INO-VT-464-CL-001; and at Screening, after the first dose of VT-464, and C2D1 for study INO-VT-464-CL-004. The Screening visit HM data was considered the baseline. Plasma levels of VT-464 (in selected pts) and 12-lead ECGs of 10-seconds duration were extracted in triplicate for each pt from the HM data at Baseline, Day 1 and C2D1 at multiple time points. Results: 57 pt screened for VT-464 treatment, underwent HM. Nonsustained ventricular tachycardia (NSVT) was seen in 6 pts (11%) prior to VT-464, providing a background estimate in this population. 37 pts were treated with VT-464 and had > 1 post-screen HM; 4 pts (11%; all with cardiac disorders) had post-treatment NSVT (all < 5 beats); no episodes of sustained VT were seen. 28 pts had ECG data extracted from HMs that coincided with peak plasma levels of VT-464. There was no QTcF or QRS prolongation; increases in the HR (mean 13.1-19.5 BPM but with a non-significant VT-464 concentration/HR relationship) and small PR increases (mean 32.9 ms; partially driven by several pts) without second degree AV block were observed. Conclusions: VT -464 did not prolong QTcF or QRS intervals and the lack of a significant exposure response HR analysis suggests that the HR increases may not be drug related. The PR prolongation is unlikely to be clinical significance. HM showed a frequency of NSVT consistent with background frequency for this pt population.A detailed examination of study pts experiencing syncope or presyncope revealed these to likely be vasovagal in nature, consistent with the increased vagal tone observed in nonclinical testing. There does not appear to be a pro-arrhythmogenic potential of VT-464 based on data from both nonclinical and clinical assessments. Clinical trial information: NCT02361086.
A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod (TASQ) in patients (pts) with mCRPC responsive to or stabilized during first-line docetaxel chemotherapy.
Authors: Fizazi Karim , Ulys Albertas , Sengeløv Lisa , Moe Mette , Ladoire Sylvain , Thiery- Vuillemin Antoine , Flechon Aude , Sabbatini Roberto , Bellmunt Joaquim , Climent Miguel Angel , Chowdhury Simon , Dumez Herlinde , Matouskova Michaela , Penel Nicolas , Liutkauskiene Sigita , Stachurski Lech , Sternberg Cora N. , Baton Frederique , Germann Nathalie , Daugaard Gedske 
Published: February 2017

201 Background: TASQ is an oral immunomodulatory, antiangiogenic and antimetastatic agent that targets the tumor microenvironment. In a phase 2 trial in mCRPC, TASQ increased PFS in chemotherapy-naive pts vs placebo (PBO) (Pili et al. JCO 2011), but there was no OS benefit in a recent phase 3 trial (NCT01234311). This study assessed whether TASQ maintenance therapy improved disease control duration in mCRPC pts with response or stabilization on first-line docetaxel (NCT01732549). Methods: Pts with mCRPC not progressing after docetaxel (min. 6 cycles; RECIST criteria; no PSA rise for last 3 tests) were assigned (1:1) to receive within 6 wks of last docetaxel administration: oral TASQ qd (0.25 mg/d rising to 1.0 mg/d over 4 wks, if tolerated) or PBO, until progression or toxicity. Randomization was stratified by visceral metastases and opioid analgesic use. Primary endpoint: radiographic PFS (rPFS) per RECIST 1.1 and PCWG 2 criteria, assessed locally. Planned sample size: 140 pts to achieve 80% power to detect an rPFS hazard ratio (HR) of 0.588 with a 1-sided α error of 0.05. Secondary endpoints: other clinical outcome measures, OS and safety. Results: From Jan 2013 to Oct 2014, 144 pts were randomized (TASQ: n = 71; PBO: n = 73) at 44 sites in 11 countries. Baseline characteristics were similar in both groups – median age: 70 yrs; visceral metastases: 23%; ECOG PS 0–1: 97%; opioid use: 15%. Median follow up: 59 wks for TASQ; 53 wks for PBO. Median rPFS (locally assessed) was 31.7 wks [90% CI 24.3–53.7] with TASQ; 22.7 wks [90% CI 16.1–25.9] with PBO (HR 0.6 [90% CI 0.4–0.9]; p = 0.0162). OS data are immature (14 deaths). Median time to next anticancer therapy: 42.3 wks [90% CI 32.0–58.0] for TASQ; 29.0 wks [90% CI 23.1–39.1] for PBO (HR 0.7 [90% CI 0.5–1.0]). TEAEs ( ≥ Grade 3): TASQ (51%); PBO (26%). TEAEs with TASQ (all grades; > 20%): decreased appetite (37%), constipation (32%), fatigue (28%), nausea (27%), arthralgia (25%), asthenia (24%) and back pain (21%). Conclusions: We believe this is the first completed trial of a maintenance strategy with a novel agent in mCRPC, an appealing concept in pts not progressing after docetaxel therapy. Clinical trial information: NCT01732549.