bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I/II study of adenovirus-mediated reduced expression in immortalized cells (REIC/DKK-3) gene therapy for prostate cancer: An interim report.
Authors: Sasaki Katsumi , Nasu Yasutomo , Watanabe Masami , Kaku Haruki , Tanimoto Ryuta , Kanbara Daiki , Watanabe Toyohiko , Yanai Hiroyuki , Kumon Hiromi 
Published: February 2017

161 Background: A new cancer therapeutic gene; REIC/Dkk-3 was found in Okayama university in 2000. In vivo experiments have demonstrated outstanding cancer-selective apoptosis effects and anti-cancer immunoactivity against various types of malignant tumors. With these positive experimental results, a phase I/II study of adenovirus-mediated REIC/Dkk-3 gene therapy for prostate cancer was initiated from January 2011 in Okayama university hospital. Methods: Two major inclusion criteria category were set up; A: A recurrence of prostate cancer following definitive endocrine therapy with/without metastasis, B: A localized prostate cancer which was considered high risk of recurrences following radical surgery according to a nomogram reported by Kattan et al. Replication-defective adenovirus vector expressing REIC/Dkk-3 (Ad-REIC) was injected directly into the prostate (or metastatic lesion in patients who received prostatectomy) in escalating doses from 1.0×1010 to 1.0×1012 viral particle (vp). Each patient in category A received total of 2 times viral injections every 4 weeks. Patients in category B also received total of 2 times viral injections every 2 weeks, then received radical prostatectomy 6 weeks after second viral injection. Results: Three patients in category A, and 9 patients in category B were entered the present study. No significant side effects were observed. In category B, signs of immunological responses in surgically removed specimens (apoptosis induction of cancer cells in TUNEL staining and infiltration of CD8 positive cells (CTL) in immunohistochemical staining) were observed in second dose. These responses were remarkably observed in the third dose. Conclusions: This initial and preliminary report suggests the favorable safety profile and positive clinical responses in a clinical trial of Ad-REIC gene therapy for prostate cancer.
Phase I trial of metronomic cyclophosphamide (CTX) and lenalidomide (LEN) in patients with castration-resistant prostate cancer (CRPC).
Authors: Wang Jue , McGuire Timothy R. , Schwarz James K. , Meza Jane L , E Talmadge James E 
Published: February 2017

164 Background: Angiogenesis and suboptimal antitumor immune response are important in the progression of CRPC. Both LEN and metronomic CTX have known anti-angiogenic and immunomodulatory activities. A phase I study of a novel combination of metronomic CTX with LEN in patients with CRPC who have failed prior docetaxel therapy was initiated to assess safety and effects on potential biomarkers. Methods: CTX was given 50 mg PO QD(day 1-28) and LEN 10-25 mg PO QD(day 1-21) on a 28 day cycle. Dose limiting toxicity was defined as any treatment-related grade 4 hematologic event or grade 3 / 4 non-hematologic event during cycles one. Quantification of circulating tumor cells (CTC), plasma cytokines, analgesic consumption and quality of life assessments were performed. Measurement of Treg and MDSCs were performed in some patients. Results: 17 patients with CRPC have been enrolled in L0-4; all patients are evaluable for toxicity. Patient characteristics include: ECOG performance status 0/1= 4/13; median age=77 (range 50–86); median PSA=36.7 (range 1.36–2287). Dose level 1 (CTX 50 mg/d, LEN 10 mg/d) was expanded to 6 patients after one out of three initial patients was removed from the study for Gr 3 gastrointestinal bleeding (in cycle 1). Dose level 1 (CTX 25 mg/d, LEN 10 mg/d) had no DLT’s. The maximum tolerated dose has not yet been reached. Other Grade 3/4 toxicities observed after cycle 1 included grade 3 pain (N=1), grade 3 neutropenia (N=4), grade 3 thrombocytopenia (N=2), grade 4 neutropenia (N=2). Most frequent grade 1 and 2 toxicities included anemia, fatigue, neutropenia, and hypocalcemia. Overall, 9 of 14 patients (64%) have experienced a reduction in PSA. One patient had partial response after one cycle. Stable disease was documented in 5 of 14 (36%) evaluable patients. Two inflammatory cytokines, IL-6 (N = 19; r = 0.64; p = 0.0035) and IL-8 (N = 9; r = 0.86; p = 0.0028), were found to significantly correlated with PSA. Conclusions: The combination of metronomic CTX and LEN can be safely administered. Preliminary clinical activity was observed in this heavily-pretreated patient population. Enrollment to this study continues and clinical and biomarker studies are ongoing.
Safety of abiraterone acetate (AA) in castration-resistant prostate cancer (CRPC) patients with concomitant cardiovascular disease.
Authors: Procopio Giuseppe , Verzoni Elena , Testa Isabella , Biasoni Davide , Torelli Tullio , Nicolai Nicola , Salvioni Roberto , Valdagni Riccardo 
Published: February 2017

168 Background: Abiraterone acetate (AA) is an inhibitor of extragonadal androgen biosynthesis that prolongs overall survival in CRPC patients who have received a chemotherapy including docetaxel. The most common adverse events related to AA therapy were fluid retention, hypertension, hypokaliemia and cardiac disorders. No safety data are available in patients with concomitant cardiac disease. Methods: Metastatic CRPC patients were enrolled in this prospective study if they were also suffering from a concomitant controlled cardiovascular disease. AA 1000 mg per day and prednisone 5 mg bid were administered orally until grade 3-4 adverse events (AE) or disease progression. The primary endpoint was the safety profile while the secondary endpoints were progression-free survival and PSA response. Results: From April to September 2011, 33 CRPC patients with concomitant cardiovascular disorders have been treated with AA. Main patients characteristics were: median age 71 years (range 57–81); baseline mean PSA value 40 ng/ml (6.32-995); the most common sites of disease were bone (27 pts, 81%), lung (11 pts, 33%) and liver (5 pts, 15%). All patients were previously challenged with at least 2 lines of hormone therapy and 1 chemotherapy regimen including docetaxel. The most common pre-existing cardiac disorders were hypertension 22 (66%), arrhythmias 4 (12%), cardiac ischemia 3 (9%) and conduction irregularity 2 (4%). Additionally 9 patients (27%) had metabolic disorders including dislipidemy and hyperglicemia. AA was feasible without inducing grade 3-4 AE nor treatment modification. The most common grade 1-2 AE were asthenia (27%), hypertension (18%) and fluid retention (28%). After a median time of treatment of 4 months (range 2–7 months) no dose modifications due to toxicity were required. No efficacy data are still available. Conclusions: Treatment with AA was feasible and well tolerated also in patients suffering from cardiac comorbidities and risk factors for cardiovascular disease.
Personal preferences and treatment choice in an intervention trial of men newly diagnosed with localized prostate cancer.
Authors: Bosco Jaclyn Lee Fong , Halpenny Barbara , Berry Donna Lynn 
Published: February 2017

170 Background: Men diagnosed with localized prostate cancer (LPC) can choose from multiple treatment regimens and are faced with a decision in which medical factors and personal preferences are important. The Personal Patient Profile-Prostate (P3P) is a computerized decision aid for men with LPC that focuses on personal preferences. We determined the proportion of men with LPC who chose a concordant treatment approach by 6-months with self-reported, influential side effects by intervention or control group, and evaluated whether the intervention (versus control) group was more likely to choose a concordant treatment. Methods: English or Spanish-speaking men diagnosed with LPC (2007–2009) from four US cities were enrolled into a randomized trial and followed at 1- and 6-months via mailed or online questionnaire. Men were randomized to receive the P3P intervention or standard education plus links to reputable websites (control group). We classified concordance as men who were (a) concerned with urinary incontinence and/or erectile dysfunction and chose radiotherapy, (b) concerned with bowel dysfunction and chose prostatectomy, (c) concerned with all three side effects and chose watchful waiting, or (d) not concerned with any side effect and chose any treatment. We calculated the proportion of concordance by group. Using logistic regression, we calculated odds ratios (OR) and 95% confidence intervals (CI) for the association between the P3P intervention and concordance. Results: Of 448 men, most were <65 years, non-Hispanic white, and had multiple physician consultations prior to study enrollment. Only 43% of the sample chose a concordant treatment given concerns about potential side effects. There was no significant difference in concordance between the intervention (43%) and control (42%) group (OR=1.1; 95%CI=0.73, 1.7). Conclusions: The P3P intervention was not associated with concordance between potential side effects and treatment choice. Information and/or physician consultation immediately after diagnosis was likely to influence decisions despite concerns about side effects. The intervention may be more effective before the first treatment options consultation.
Heavy ethanol intake and elevated prostate cancer risk among men with previous negative biopsies in the REDUCE trial.
Authors: Banez Lionel Lloyds , Hoyo Cathrine , Gerber Leah , Moreira Daniel M. , McKeever Madeline G , Andriole Gerald L. , Freedland Stephen J. 
Published: February 2017

187 Background: Whether ethanol intake contributes to prostate cancer (CaP) risk is debated. Although ethanol was found to contribute to increased CaP risk in the Prostate Cancer Prevention Trial, whether ethanol intake impacts CaP risk among men with previous negative biopsies has not been previously assessed. We therefore examined the relationship between ethanol consumption and CaP risk in the REDUCE trial and further sought to determine whether ethanol intake modifies the effect of dutasteride in reducing CaP risk. Methods: This is secondary analyses using data from 6,729 men who had at least one on-study biopsy while participating in the REDUCE trial. Ethanol intake, which was expressed as units (½ pint of beer or 1 glass of wine, etc.) per week, was analyzed as a continuous and three-tiered categorical variable [non-drinker, moderate (≤7 units/week), heavy-drinker (>7 units/week)]. Risks for overall and high-grade (Gleason ≥7 vs. Gleason<7 CaP or biopsy negative) CaP were evaluated using logistic regression adjusting for clinical parameters including dutasteride intake. Test for interaction was used to determine whether the association between dutasteride and CaP risk is influenced by ethanol. Results: Forty-nine percent were moderate-drinkers and 26% were heavy-drinkers. On a continuum, increased ethanol intake was significantly associated with elevated risk for overall (p=0.035) and high-grade CaP (p=0.048). Compared to non-drinkers, heavy drinkers were at increased risk for overall (OR 1.21; 95% CI 1.02-1.43; p=0.03) and high-grade CaP (OR 1.34; 95% CI 1.01-1.78; p=0.04). Risks for overall (p=0.55) and high-grade CaP (p=0.21) were comparable between moderate- and non-drinkers. Dutasteride reduced overall CaP risk (OR 0.73; p<0.001) and ethanol intake did not modify the effect of dutasteride on CaP incidence (p-interaction=0.64). Conclusions: Among low-risk men with at least one prior negative prostate biopsy, heavy ethanol intake is associated with increased risk for overall and high-grade CaP. In contrast to CaP prevention with finasteride, which appears to be inhibited by heavy ethanol intake, consumption of ethanol does not negatively impact CaP prevention with dutasteride.
Impact of androgen deprivation therapy (ADT) on bone mineral density (BMD) over 3 years in men with nonmetastatic prostate cancer.
Authors: Alibhai Shabbir M.H. , Mohamedali Hassanabbas Z. , Panju Abbas H. , Timilshina Narhari , Breunis Henriette , Duff Canning Sarah , Fleshner Neil Eric , Krahn Murray , Naglie Gary , Tannock Ian , Tomlinson George A. , Warde Padraig Richard , Cheung Angela M 
Published: February 2017

193 Background: Decreased BMD is a common side effect of ADT, leading to increased fracture risk. Although loss of BMD appears to be greatest within the first 12 months of starting ADT, few data on BMD changes exist beyond 12 months, and other risk factors for bone loss in men on ADT are not well-characterized. Methods: Men age 50+ with non-metastatic prostate cancer and starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual-energy x-ray absorptiometry at baseline and yearly for 3 years. A matched control group of men with prostate cancer but not on ADT was also enrolled. Medication use was recorded at each visit. Multivariable regression analyses were done to examine predictors of BMD loss. Results: 80 ADT users and 80 controls were enrolled (mean age 69.4 y); 49.7% had osteopenia and 4.6% had osteoporosis at baseline. ADT was associated with significant losses in lumbar spine BMD in year 1 compared to controls (p=0.004) and trends towards greater declines at femoral neck and total hip sites. Changes in year 2 and 3 were much smaller and not statistically different from controls (Table). Vitamin D use but not calcium use was associated with improved BMD at the lumbar spine in year 1 (+5.77%, p=0.006) with positive trends at other sites (+2.19% femoral neck, +1.76% total hip) primarily in year 1. Age was not associated with changes in BMD. Conclusions: Losses in BMD with ADT use are greatest at the lumbar spine and in the first year compared to years 2 and 3 and are independent of age. Vitamin D appears to be protective particularly in the first year of ADT use. [Table: see text]
Response to ketoconazole (keto) or docetaxel (D) following clinical progression on abiraterone acetate (AA) in castrate-resistant prostate cancer (CRPC).
Authors: Aggarwal Rahul Raj , Formaker Carl , Small Eric Jay , Molina Arturo , Ryan Charles J. 
Published: February 2017

196 Background: Patients (pts) with CRPC treated with keto often experience a rise in serum adrenal androgen levels upon progression and may subsequently respond to more potent adrenal suppression with AA. In contrast, pts treated with AA do not have a rise in serum androgen levels upon progression, and thus may not respond to further androgen synthesis inhibition with keto but require other treatment modalities such as chemotherapy instead. The goal of this analysis is to report the outcomes of pts with CRPC progressing on AA subsequently treated with either keto or D. Methods: Pts with chemotherapy-naïve CRPC were treated on previously reported phase 1 and 2 trials of AA, with doses ranging from 250 to 1000 mg/day. Subsequent treatment following progression on AA was per individual investigator discretion, including treatment with either keto or D. Results: To date, following disease progression on AA, 6 and 14 pts have been subsequently treated with either keto or D respectively. Of the 14 pts treated with D, 11 (79%) had exposure to keto prior to AA. The keto- and D-treated cohorts were similar with respect to other baseline factors, including prior response to AA (4/6 (67%) pts with > 50% PSA decline on AA in keto cohort; 10/14 (71%) pts in D cohort); though pts treated with D were more likely to require opioid analgesics (0 pts in keto cohort; 7 (50%) in D). For pts treated with keto, none experienced a decline in PSA, improvement in bone scan, or an objective response; all had disease progression by 12 weeks. In contrast, for pts treated with D, 10 (71%) had a decline in PSA; 6 (43%) with a > 50% maximum PSA decline. Of 6 pts with measurable disease, 2 (33%) had an objective response. The median time to progression for the D cohort was 129 days (range 60 – 294). Conclusions: Although the cohort size is small, and post-AA therapy was not randomized, these data provide preliminary support for the hypothesis that CRPC progressing on AA is cross-resistant to further androgen synthesis inhibition with keto. Contrary to other reports, prior treatment with AA does not appear to decrease the likelihood of subsequent response to D, but this observation requires prospective validation.
The impact of neoadjuvant hormone therapy on the permanent 125I-seed brachytherapy for low- or intermediate-risk prostate cancer.
Authors: Tanimoto Ryuta , Bekku Kensuke , Ebara Shin , Araki Motoo , Yanai Hiroyuki , Katayama Norihisa , Nasu Yasutomo , Kumon Hiromi 
Published: February 2017

201 Background: To determine whether neoadjuvant hormonal therapy improves the biochemical outcome for men with low or intermediate risk prostate cancer and undergoing permanent brachytherapy. Methods: From January 2004 to April 2011, 449 patients with low-risk (221 men) or intermediate-risk (228 men) based on NCCN guideline underwent transperineal ultrasonography-guided permanent 125I-seed brachytherapy. Of these patients, 186 received neoadjuvant hormonal therapy (NHT). The median patient age was 67 years. The median follow-up (SD) was 48 (20) months (calculated from the day of implantation). Biochemical disease-free (BDF) survival was defined using Phoenix definition. The clinical variables evaluated for BDF survival included presence of NHT, Gleason score, clinical T-stage and pretreatment PSA. Results: For all patients, the 1, 3, 5-year actuarial BDF survival rates were 99.2%, 96.2% and 90% without NHT, 100%, 97.2%, 91.0% with NHT (p=0.954). When stratified by risk group, NHT did not improve the outcome for patients at low risk (P = 0.745) or at intermediate risk (P = 0.888). The duration (<= 5 vs >5 months) or combinations (single vs combined androgen blockade) of hormonal therapy were not statistically significant in predicting biochemical recurrence. In a multivariate analysis (shown below), only the Gleason score was a strong predicting factor, while NHT as well as pretreatment PSA, T stage were insignificant. Conclusions: In patients treated by permanent prostate brachytherapy, NHT did not improve the biochemical outcome for those at low-risk or intermediate-risk features. Furthermore, the duration or combinations of hormonal therapy conferred no additional biochemical advantage. [Table: see text]
Injection of hyaluronic acid (HA) to better preserve the rectal wall in prostate hypofractionated radiotherapy (HFR).
Authors: Chapet Olivier , Udrescu Corina M , Ruffion Alain , Sotton Marie-Pierre , Devonec Marian , Vincent Marion , Zahra Nabil , Mazzara Christophe , Colombel Marc , Azria David , Jalade Patrice 
Published: February 2017

202 Background: Several studies are in favor of an α/β ratio of less than 3Gy for prostate (P) cancer, encouraging HFR. However, the development of such radiation patterns can only be done if the risk of rectal toxicity is well controlled. The objective of the present study was to evaluate the contribution of an injection of HA between the rectum and the P to reduce the risk of rectal toxicity in a HFR approach. Methods: A phase II study of HFR at 62Gy in 20 fractions (BED = 84Gy; α / β = 1.5Gy) is currently conducted. A transperineal injection of 10cc of HA (NASHA Spacer gel, Q-Med AB, Uppsala, Sweden) is systematically performed, between the rectum and the P, under local anesthesia and under ultrasound guidance. A dosimetric CT scan is performed before (CT1) and after injection (CT2). Patients are treated with a 7 beams IMRT plan, optimized on the CT2. For the first 10 patients included in the study, the same treatment plan was optimized on CT1. The rectum was empty on the 2 CTs and defined from 2cm above the seminal vesicles to 2 cm below the P. The rectal wall was defined by an internal expansion of 5 mm. The volumes of rectum irradiated, with and without HA, were compared on the following dosimetric parameters: maximum dose (D max), dose to 2.5cc (D2.5), 5cc (D5) and 10cc (D10) of rectal wall and volume of rectum receiving 90% (V90), 80% (V80) and 70% (V70) of the prescribed dose of 62Gy. To limit a potential impact of variation of rectal volume between the two CT, all results are given in cc and not in % of volume. Results: The mean P volume was 52.4cc (30cc - 93.8cc) on the CT1 and 52cc (32.5 - 92.7) on the CT2. The injection of HA reduced the mean D max value to the rectal wall of 4.5Gy (57.5Gy vs 62 Gy). The mean values of V90, V80, and V70 are reduced by 69% (1.9cc vs 6.1cc), 46% (4.5cc vs 8.4cc) and 32% (7.4cc vs 10.9cc). Same way, the average values of D2.5, D5 and D10 are reduced by 6.2 Gy (54.6Gy vs 60.8Gy) 9.3Gy (49.0Gy vs 58.3Gy) and 7.8Gy (39.7Gy vs 47.5Gy). Conclusions: In this study, the injection of HA limited the doses to the rectal wall. These results suggest that late toxicities could be significantly reduced. A phase II study is underway to assess the rate of late rectal toxicities when a HFR at 62Gy in 20 fractions is combined with an injection of HA.
Does salvage radiation therapy (SRT) change the biology of recurrent prostate cancer (PCa) based on PSA doubling times (PSADT)? Results from the SEARCH database.
Authors: Muller Roberto Lodeiro , Presti Joseph C. , Aronson William J , Terris Martha K. , Kane Christopher J , Amling Christopher L , Freedland Stephen J. 
Published: February 2017

203 Background: SRT offers a second opportunity for PCa control after biochemical recurrence in men treated with radical prostatectomy. Although some retrospective data suggest an overall survival benefit, we hypothesized that in men with radio-resistant tumors, SRT may indeed promote transformation to a more aggressive cancer due to radiation-induced mutations. To test this, we used PSADT as a surrogate for cancer aggressiveness and compared PSADT before and after SRT in men who failed SRT. Methods: Of 288 men who underwent SRT in the Shared Equal Access Regional Cancer Hospital (SEARCH) database since 1988, we detected 78 with SRT failure defined as PSA ≥ 0.2 ng/mL above the post-SRT nadir. Of these, 44 had PSADT available before and after SRT, which was compared using Wilcoxon’s paired test with men serving as their own controls. We also tested predictors of PSADT change using multivariable logistic regression. Results: There were no differences in PSADT before and after SRT (10.6 vs. 12.2 months; P=0.85). However, in some individual cases large changes were observed. Only seminal vesicle invasion showed a trend towards an association with a shorter post-SRT PSADT relative to the pre-SRT PSADT (P=0.067). Conclusions: Overall, the PSADT after and before SRT were statistically similar suggesting that after SRT failure, PCa does not emerge with more aggressive biologic features. Further studies are needed to identify predictors and the clinical relevance of individual PSADT changes noted in our study. (Note: Authors R. L. Muller and S. J. Freedland received support from DoD Award Number W81XWH-10-1-0155).