bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survey on management of metastatic hormone-refractory prostate cancer upon progression during or following first-line chemotherapy in five European countries.
Authors: Auziere Sebastien , Flinois Alain , Obi-Tabot Eliot , Rose Mathieu , Parnaby Adam 
Published: February 2017

232 Background: In Europe, docetaxel is the standard first-line (1L) chemotherapy for patients with metastatic hormone-refractory prostate cancer (mHRPC). Upon progression, either during or after 1L chemotherapy, treatment options are limited. This study evaluated how patients who progressed during or after 1L docetaxel between October 2009 and June 2010 were managed. Methods: A representative sample of 349 physicians (oncologists, urologists) who managed patients with mHRPC selected from Germany, France, United Kingdom, Spain and Italy were surveyed. Information on the treatments used at the time of progression (during or within the first 6 months following 1L treatment with docetaxel was provided. Results: Information on a total of 2,870 mHRPC patients was provided of which 2,670 (94 %) had received docetaxel in 1L. 1,389 (52%) patients progressed during 1L docetaxel or within 6 months following treatment; of these, 615 (44 %) received as 2L chemotherapy the agents listed in the table. Conclusions: In this study, mitoxantrone was the most commonly used chemotherapy agent for 2L treatment of patients with mHRPC who progressed during treatment or within the first 6 months following the end of 1L. Docetaxel rechallenge was uncommon for patients experiencing progression early, during or after the end of 1L. [Table: see text]
Physical activity and prostate cancer risk reduction: Does race matter?
Authors: Singh Abhay A , Antonelli Jodi A , Jones Lee , Gerber Leah , Calloway Elizabeth Ellen , Shuler Kathleen , Hoyo Cathrine , Grant Delores , Freedland Stephen J. , Banez Lionel Lloyds 
Published: February 2017

235 Background: We previously reported that physical activity may reduce prostate cancer (CaP) risk among men undergoing prostate biopsy. However, whether the potential benefit of exercise against cancer differs by race is unclear. We therefore sought to further characterize the link between physical activity and CaP risk as a function of race. Methods: Men undergoing prostate biopsy at the Durham VA Hospital were asked to complete a survey assessment of current exercise habits including frequency of differing intensities (mild, moderate and strenuous) as well as the average duration. Total current exercise was calculated by multiplying the frequency of sessions within each intensity by their average duration, weighted by the estimated metabolic equivalent (MET) and then summed across all intensities expressed as average total MET hrs/wk. Specifically, exercise intensities were as follows: mild (3 METs, e.g. easy walking), moderate (5 METs, e.g. tennis), and strenuous (9 METs, e.g. running). Quantified exercise was compared between race groups using rank sum test. Associations between exercise and CaP risk was determined using crude and adjusted logistic regression stratified by race. Results: A total of 308 men had complete data for analysis. Of these men, 53% were white and 47% were black. There was no significant difference in the amount of physical activity between race groups (p= 0.11). Increased amount of exercise was associated with decreased CaP risk for white men in both crude (OR= 0.89; 95% CI=0.81–0.98; p=0.02) and adjusted (OR=0.90; 95% CI=0.82−0.99; p=0.04) regression models that controlled for age, BMI, DRE, previous biopsy, and family history of CaP. We found no association between exercise and CaP risk among black men in both crude (p=0.79) and adjusted regression models (p=0.87). Conclusions: Increased physical activity was associated with CaP risk reduction among white men but not among black men. Further investigations to validate this potential source of CaP race disparity and to identify exercise-specific parameters that influence CaP risk reduction (ex. age-specific or cumulative exercise) are required. Investigating the race-specific mechanisms through which exercise modifies CaP risk is also warranted.
Circulating tumor cells (CTCs) as a predictor of metastatic disease in patients with biochemical recurrence (BR) of prostate cancer with equivocal scan results.
Authors: Aragon-Ching Jeanny B. , Simmens Samuel J. , Patierno Steven R. , Siegel Robert S. 
Published: February 2017

239 Background: Staging for BR is challenging since the yield of computed tomography (CT) and bone scans are low, especially in patients with low prostate specific antigens (PSA) levels. We examined the utility of circulating tumor cells (CTCs) to predict metastatic disease in a cohort of patients who presented with BR (Aragon-Ching, et. al. ASCO GU 2011;abstr 60). Methods: 33 pts enrolled from May 2010 to September 2011 with BR, defined as patients (pts) who have undergone primary treatment with PSA rise to >/= 0.2 from a prior undetectable level for prior prostatectomy or > 2 mg/dl rise from post-nadir radiotherapy, were included. PSA doubling time (PSADT), scan results, Gleason scores, age, testosterone levels were all obtained. CTCs were evaluated in 7.5 mL of peripheral blood using the CTC CellSearch test. BR patients with equivocal CT and/or bone scan results who were biopsiable and consentable underwent bone biopsy to confirm metastatic disease. Results: The median age for 33 patients was 71 y/o (range: 51 – 91), median PSA of 1.7 ng/mL (range 0.2 – 65.8), testosterone levels of 315.5 ng/dL (range: 31 – 727), Gleason score of 7, hemoglobin of 13.78 g/dL, BMI of 27.72 and alkaline phosphatase of 68 IU/L. Prostatectomy was the primary treatment in 23 pts, radiotherapy in 9 pts and Cyberknife in 1 pt. Median PSADT varied between 0.35 to 55.2 months. Only a small number of patients had either biopsy confirmed metastatic disease (n=2) or detectable CTC (n=3). Both of the 2 patients with metastatic disease had detectable CTC (sensitivity = 1.00, 95% CI: .34, 1.00). For the patients without signs or confirmation of metastatic disease, 30/31 had no detectable CTC (specificity = .97, 95% CI: .84, .99). Conclusions: While most pts with BR have negative blood CTCs, patients with detectable CTCs and equivocal findings on scans should raise suspicion and prompt a search for metastatic disease, given increasing available treatment options for metastatic prostate cancer. However, the limited number of patients may preclude reliable statistical evaluation of CTCs in this population. Supported by IRG-08-091-01 from ACS to GWU Cancer Institute.
A combination herbal supplement for biochemically recurrent prostate cancer.
Authors: Dorff Tanya B. , Hawes Debra , Tsao-Wei Denice D. , Quinn David I. , Goldkorn Amir , Lieskovsky Gary , Vogelzang Nicholas J. , Groshen Susan G. , Pinski Jacek K. 
Published: February 2017

24 Background: After curative local therapy, thousands of men will have rising PSA as an early indicator of recurrent prostate cancer. For them, no standard of care exists, and concern over serious side effects of androgen deprivation (ADT) makes delaying ADT common. We tested Prostate Health Cocktail (PHC), which contains vitamins D & E, saw palmetto, lycopene, green tea and soy extracts, in this population, to see whether it could induce PSA declines. Methods: Eligible men had rising PSA with doubling time (DT) 3-36 months, with no evidence of metastases on CT and bone scans. After IRB approval, 28 men were treated with PHC 3 capsules PO daily for 4 week cycles. PSA was repeated after the first cycle, then every 2 cycles with imaging only as clinically indicated; the primary endpoint was PSA decline. PSA progression was defined as 25% increase and absolute increase of 5 ng/mL or return to baseline. Circulating tumor cells (CTCs) were measured at baseline and after 3 cycles using parylene membrane filters. Results: The median age was 67 (range 54-84) and baseline PSA was 2.9 ng/mL (1.1-53.2); the median number of cycles was 6 (1-13). Stable PSA was the best response for 23/28 men (83%) and 8/27 men (29.6%) had a PSA decline (1.1%-29.4% maximum decrease). 47% stopped therapy for progression with median time to progression=9.2 months. There was no association between Gleason score or baseline PSA, vitamin D or selenium level and PSA decline. CTCs were detected in 5 of the first 23 subjects. The median PSA for these men was 2.77 ng/mL (range 1.63-16.8). There was no significant change in testosterone or DHT during treatment. Median PSA DT at baseline was 7.8 months (range 3-36). One patient had grade 3 transaminitis in the setting of alcohol consumption, otherwise toxicities were limited to grade 1 or 2 hypercalcemia(1), hyperkalemia(2), hyperglycemia(4), flatulence(4), other GI(5), and rash(1). Conclusions: PHC demonstrated activity in men with biochemically recurrent prostate cancer, resulting in PSA declines in nearly a third of cases, and was not associated with changes in serum androgens or significant toxicities. For the first time, we are reporting that circulating tumor cells can be detected in men with biochemical recurrence using filter technology.
Ipilimumab (IPI) in metastatic castrate-resistant prostate cancer (mCRPC): Results from an open-label, multicenter phase I/II study.
Authors: Slovin Susan F. , Hamid Omid , Tejwani Sheela , Higano Celestia S. , Harzstark Andrea , Alumkal Joshi J. , Scher Howard I. , Chin Kevin M. , Gagnier Paul , McHenry M. Brent , Beer Tomasz M. 
Published: February 2017

25 Background: IPI is a fully human, anti-CTLA-4 monoclonal antibody capable of enhancing anti-tumor immunity. Preclinically, radiotherapy (XRT) and CTLA-4 blockade have synergistic anti-tumor activity. This phase 1/2 study in patients (pts) with mCRPC was designed to assess: safety of IPI at various doses, feasibility of combining IPI with XRT, and activity. Methods: mCRPC pts with or without prior chemotherapy were enrolled. In the dose-escalation phase, 33 pts (³6 pts per cohort) received IPI q3 weeks x 4 doses at 3, 5, or 10 mg/kg, or with XRT at 3 or 10 mg/kg. Single dose XRT (8 Gy/lesion, up to 3 lesions per pt) was given 24 to 48 h before the first IPI dose. The 10 mg/kg ± XRT cohorts were expanded to 50; 34 received IPI + XRT (Table). Based on clinical benefit, pts received additional doses of IPI. Endpoints were safety, and activity as assessed by serum prostate-specific antigen (PSA) and RECIST criteria. PSA was monitored monthly, with scans q3 months (mos). Results: There were no dose-limiting toxicities; 10 mg/kg ± XRT cohorts were, therefore, expanded for phase 2 evaluation. Treatment-related adverse events (AEs) and immune-related AEs (irAEs) were common across all cohorts with or without XRT. Common (≥ 15%) treatment-related AEs of any grade in the 10 mg/kg ± XRT group were fatigue (50%), diarrhea (54%), nausea (24%), colitis (22%), decreased appetite (22%), vomiting (18%), rash (32%) and pruritus (20%). Most common grade 3/4 irAEs were colitis (16%), diarrhea (8%) and hepatitis (10%). irAEs were generally responsive to immunosuppressives. Of 50 PSA-evaluable pts in the 10 mg/kg ± XRT group, 8 had PSA response (Table) lasting between 3 and 13+ mos. Of the 28 tumor-evaluable pts receiving 10 mg/kg ± XRT, 1 had complete response and 6 had stable disease. Conclusions: In pts with mCRPC, IPI 10 mg/kg alone or in combination with XRT showed clinical antitumor activity with disease control in some patients, and a generally manageable safety profile. The combination (IPI 10 mg/kg ± XRT) and monotherapy (IPI 10 mg/kg) are being explored in randomized phase 3 trials. [Table: see text]
First results of a phase II trial to assess the efficacy of efavirenz in patients with metastatic androgen-independent prostate cancer.
Authors: Houede Nadine , Pulido Marina , Mourey Loic , Joly Florence , Ferrero Jean Marc , Bellera Carine , Priou Franck , Lalet Caroline , Laroche Audrey , Canal-Raffin Mireille , Piazza Pier Vi 
Published: February 2017

251 Background: This Phase II trial assessed the efficacy of efavirenz, a non-nucleoside reverse transcriptase inhibitor in patients with asymptomatic HRPC [hormone refractory prostate cancer] who progressed, before docetaxel based chemotherapy. Preclinical studies showed that efavirenz, via Line-1 inhibition, could block proliferation and induced re-differentiation of prostate cancer cell line. We then investigated if efavirenz treatment can delay biological and clinical progression. Methods: The primary objective was to assess the efficacy of efavirenz in patients, with no clinical symptom related to disease progression. Each patient received efavirenz 600 mg/day until objective biological progression or study discontinuation. It was possible to increase the dose (up to 1200 mg daily) in case of PSA progression at 3 months. Efficacy was measured in terms of 3-month non-progression. Based on a 2-stage Simon’s design, a total of 16 non-progressions out of 54 eligible patients were required to claim efficacy. Results: 61 patients were enrolled in the study with 53 eligible for the primary endpoint. At baseline, median age was 71 years and median PSA level was 49.6 ng/mL. A total of 15/53 (28%) non-progressions were observed at 3 months. As patients are still being followed, overall survival, PSA progression free survival and symptomatic progression free survival at one year will be presented. Sixty patients were assessable for toxicity. Of these, 9 (15%) experienced at least one grade III/IV toxicity i.e. neuropsychiatric adverse events already reported in efavirenz-treated HIV patients. With regard to pharmacokinetics (PK), preliminary data indicates variability in the 3-month efavirenz concentration. Ongoing preliminary analyses suggest a better response in patients with elevated (>3000ng/ml) plasmatic concentration. Conclusions: Current analyses do not allow to claim efficacy of Efavirenz at the 600 mg dose. The ongoing analysis of the relationship between plasmatic concentration of efavirenz and treatment efficacy could confirm that higher doses of efavirenz may constitute an efficient treatment. A phase I dose escalation study is currently being performed.
Use of radiographic progression to predict overall survival in men with castration-refractory prostate cancer.
Authors: Kamoi Kazumi , Okihara Koji , Takaha Natsuki , Iwata Tsuyoshi , Kawauchi Akihiro , Miki Tsuneharu 
Published: February 2017

254 Background: The purpose of this study was to analyze prognostic factors to predict overall survival in patients with castration-refractory prostate cancer (CRPC). Methods: A total of 68 patients with CRPC treated by secondary hormonal therapy (dexamethasone) and/or chemotherapy including docetaxel were analyzed. Primary endpoint was survival after PSA relapse. PSA relapse was defined as 3 consecutive PSA increase and serum PSA more than 4 ng/ml. Factors analyzed to predict survival were initial PSA value, initial clinical stage, pathological tumor grade (WHO grade), time to PSA relapse, nadir PSA value, time to nadir PSA, age at PSA relapse, PSA value at relapse, radiographic progression revealed by bone scan or CT scan, and bone pain. Univariate and multivariate analysis were performed using Cox regression hazard model. Results: Univariate analysis revealed nadir PSA value, time to nadir PSA, PSA value at relapse, radiographic progression revealed by bone scan or CT scan, and bone pain were significant predictors (p<0.05). Multivariate analysis revealed only radiographic progression was the independent predictor for survival after PSA relapse (p=0.039). Median survival time was 63.5 and 23.5 months in patients with (n=39) and without (n=29) radiographic progression, respectively (log-rank p=0.0002). Median survival time in 39 patients with radiographic progression in bone (n=31), lymph nodes (n=6), visceral lesion (n=3), and local lesion (n=4) were 23.5, 5, 2, and 12.5 months, respectively. Conclusions: For patients with PSA relapse after hormonal therapy, the finding of radiographic progression was the only independent factor to predict overall survival.
A QTc study of cabazitaxel in patients with advanced solid tumors.
Authors: Wade James Lloyd , Dakhil Shaker R. , Baron Ari David , Rottey Sylvie , Millard Frederick E. , Daugaard Gedske , Machiels Jean-Pascal H. , Conkright William A. , Sharma Sunil , Soetekouw Patricia M.M.B. , Yachnin Jeffrey , Sengeløv Lisa , van Veldhuizen Peter , Agarwala Sanjiv S , Nguyen TX Quyen , Chadjaa Mustapha , Maison-Blanche Pierre 
Published: February 2017

257 Background: Cabazitaxel (Cbz) improves overall survival in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure, compared with mitoxantrone (HR 0.70; 95% CI 0.59–0.83; P < 0.0001). Following Cbz approval for the treatment of mCRPC, this study was undertaken to evaluate any effect of Cbz on the QTc interval. Methods: This prospective, multinational, open-label study ( NCT01087021 ) enrolled pts with advanced solid tumors (without other therapeutic options). Cbz 25 mg/m² IV was administered on Day 1 Q3W. QTc and other ECG intervals were assessed on Day 1 of Cycle 1. Triplicate ECGs were obtained from 12-lead Holter recordings and concomitant serial blood samples were collected for pharmacokinetic (PK) analysis. The primary endpoint was change from baseline in the corrected QTc interval (according to the Fridericia formula QTcF). Results: A total of 96 pts were enrolled; 32 pts under the original protocol (6-h Holter) and 64 pts following protocol amendment 1, which extended ECG and PK monitoring (24-h Holter). Median age was 63 yrs (69.8% male), 30.5% and 57.9% of pts were ECOG PS 0 and 1 respectively; 33 pts (34.4%) had prostate cancer. Screening ECG was abnormal but not clinically significant in 39.6% of pts. The majority (n = 65) of pts received ≥ 3 treatment cycles; safety and ECG parameters were evaluated in 95 and 94 pts, respectively. In the 24-h Holter group (n = 63), the maximum least squares (LS) mean change from baseline in QTcF was 4.8 msec (90% CI 2.1–7.5), returning to baseline by 24 h. Similar results were observed in the overall population (n = 94). At Cmax, Cbz concentration had no effect on QTcF change from baseline; the mean (CV%) Cmax (n = 91) and AUC (n = 92) were 276 ng/ml (63%) and 1245 ng.h/ml (82%). The LS mean change from baseline in heart rate increased up to 24 h but remained < 10 beats per minute. The most common Grade 3/4 AEs were neutropenia (27.4%), febrile neutropenia (12.6%), fatigue (12.6%) and dehydration (5.3%). No Grade 3/4 cardiac AEs were reported. Of the 6 deaths reported, 1 (infection) was study drug related. Conclusions: Cbz had no significant effect on QTc interval in pts with advanced tumors. The Cbz safety profile is consistent with previous findings and with other taxane-based therapies.
Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: First results from STAMPEDE (MRC PR08, CRUK/06/019), a randomized controlled trial.
Authors: James Nicholas David , Sydes Matthew Robert , Mason Malcolm David , Clarke Noel W , Anderson John , Dearnaley David Paul , Dwyer John , Jovic Gordana , Ritchie Alastair SW , Russell J. Martin , Sanders Karen , Thalmann George , Bertelli Gianfilippo , Birtle Alison J , O'Sullivan Joe M. , Protheroe Andrew , Sheehan Denise , Srihari Narayanan , Parmar Mahesh ,   STAMPEDE Investigators
Published: February 2017

26 Background: Long-term hormone therapy (HT) alone is standard of care for men with metastatic or high-risk non-metastatic prostate cancer (PCa). STAMPEDE investigates whether early use of additional therapies improves overall survival. It is an international randomised controlled trial ( NCT00268476 ) using novel multi-arm, multi-stage methods to assess adding 1 or 2 of three agents (docetaxel, zoledronic acid (ZA), celecoxib) in 5 research arms in men with PCa starting long-term HT for the first time. Methods: HT was given as per standard care. Celecoxib was planned as 400mg bid until the sooner of 1 year or disease (including PSA) progression. The trial has 3 intermediate activity stages (I-III) where the outcome measure (OM) is failure-free survival (FFS) and 1 final efficacy stage (IV) with overall survival as primary OM. At the end of each stage, research arms are compared pairwise to the control arm. Accrual of further patients is discontinued early for any research arm either showing (a) safety concerns or (b) insufficient evidence of activity (lack-of-benefit) where the treatment effect on FFS is compared against a pre-defined stopping guideline. The interim activity “hurdle” becomes increasingly stringent stage-by-stage. Results: From Oct-2008 to Feb-2011, 2114 patients were consented and randomised, including 875 in this comparison. With 205 control FFS events, there was evidence of insufficient activity for HT+celecoxib over HT-alone: HR 0.98 (95%CI 0.90-1.06). The Independent Data Monitoring Committee recommended stopping accrual to this arm; stopping celecoxib was also recommended for patients currently on treatment. (Accrual was also stopped to HT+celecoxib+ZA but data are not disclosed.) There was no evidence of differences in toxicity: 25% and 23% of patients reporting grade ≥3 toxicities or adverse events with or without celecoxib. Control arm FFS was 51% at 2 years, in line with expectations. Conclusions: Celecoxib shows no evidence of activity in this setting. Accrual continues seamlessly to the other research arms. Follow-up of all arms is ongoing. Support: MRC, Cancer Research UK, Novartis, Sanofi-Aventis, Pfizer.
Flexible trial design in practice: Dropping and adding arms in STAMPEDE (MRC PR08, CRUK/06/019)—A multiarm, multistage randomized controlled trial.
Authors: Sydes Matthew Robert , James Nicholas David , Mason Malcolm David , Clarke Noel W , Amos Claire , Anderson John , De Bono Johann Sebastian , Dearnaley David Paul , Dwyer John , Jovic Gordana , Ritchie Alastair SW , Russell J. Martin , Sanders Karen , Thalmann George , Parmar Mahesh ,   STAMPEDE Investigators
Published: February 2017

27 Background: STAMPEDE ( NCT00268476 ) is a multi-centre, RCT using novel multi‐arm, multi‐stage (MAMS) methods. We describe the methodological and practical issues arising with early stopping of recruitment to some arms following an intermediate analysis and the issues in adding new research arms during the trial. Methods: The trial recruits men with locally advanced or metastatic prostate cancer starting standard long-term hormone therapy. There are 5 research and 1 control arm assessed over 3 intermediate activity stages I-III [outcome measure: failure-free survival (FFS)] and a final efficacy stage IV [outcome measure: overall survival]. At the end of each stage, research arms are formally compared to the control arm. Accrual of further patients is discontinued early for research arms not showing sufficient evidence of activity or with adverse safety considerations; accrual continues to the other arms; this interim hurdle is increasingly stringent at each stage. The addition of new research arm(s) can be actively considered when sufficiently interesting agents emerge. New research arms are compared only to contemporaneously-recruited control arm pts using the same intermediate guidelines in a time-delayed manner. Results: (1) After the second intermediate activity analysis (Mar-2011), the IDMC recommended and the Trial Steering Committee ratified discontinuation of recruitment to two research arms for lack-of-sufficient activity. Nearly 100 recruiting centres in UK and Switzerland had to promptly implement changes. Detailed advanced preparation meant that activation was swift and recruitment continued seamlessly into Activity Stage III. (2) An application to add a new research arm, abiraterone, has been agreed by funders, industry partner and ethics committee; regulatory approval awaited. Details on methodological and practical issues and implementation of these changes will be presented. Conclusions: The STAMPEDE experiences shows that recruitment to MAMS trials is achievable and that mid-flow changes to trial design are practicable and encouraged.