bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemotherapy in hormone-refractory prostate cancer: Docetaxel with and without VT122.
Authors: Bhattacharyya Gouri Shankar , Bascomb Newell , Malhotra Hemant , Biswas Ghanashyam , Bondarde Shailesh Arjun 
Published: March 2020

e16062 Background: Randomized study in metastatic castration resistant prostate cancer treated with docetaxel and the benefit of adding VT122. Methods: Castration resistant prostate cancer with bone metastasis, symptomatic were treated with docetaxel 75 mg/m2 every 3 week and prednisolone with continued androgen suppression, LHRH analogue and zoledronic acid, every 28 days with or without VT122. VT122 is a drug combination of etodolac, a COX-2 inhibitor and propranolol, a beta blocker with anti angiogenic properties; this combination has previously been shown to be anti cachectic, anti neoplastic.The dose of etodolac was titrated by C-reactive protein levels to a maximum of 800 mg/day. The dose of propranolol was titrated to keep heart rate at around 60 b/min to 70 b/min. GCSF was allowed, all patients were given Calcium and VitaminD. The primary end point was time to progression, a composite end point of objective progression by RECIST criteria, PSA progression or pain progression, whichever occurred first was applied.The McGill questionnaire was applied to patients. Number of patients 69; 34 in docetaxel arm; 35 in VT122 arm. Age between 50-65 years. Taken from 3 centers with PS ECOG <2 controlled comorbidity with stable analgesic regime. All patients were planned for 6 cycles of docetaxel. Follow-up was for a period of two years. Results: Median age of 62 years with ECOG status 1 was seen in 88%. The median PSA value was seen as 138 ng/ml (10 - 600). 66% in both arms had measurable disease. Conclusions: Addition of VT122 improves response rates, duration of response and symptom scales along with 1-year survival which are statistically significant; toxicities are also significantly decreased and indicating increased efficacy and safety profile of docetaxel. The efficacy and control of toxicity and easy to administer makes this an attractive combination. [Table: see text]
Effectiveness of abiraterone as salvage therapy in patients with docetaxel- and castration-resistant prostate cancer (mDCPC) that progressed during second-line chemotherapy with carboplatin plus weekly docetaxel (DC).
Authors: Morgan Michael A. , Fenner Martin , Grünwald Viktor , Merseburger Axel S. , Ganser Arnold , Reuter Christoph W. 
Published: March 2020

e16064 Background: Our recent data have shown that carboplatin AUC5 on d1 plus docetaxel at a dose of 35 mg/m2 iv on d1, 8, 15 every 4 weeks (q4w) is an effective salvage therapy in mDRPC. Patients (pts) who have progressive disease during DC treatment survive only ~7 months and many are symptomatic. We have demonstrated that high free testosterone (FT) serum levels during DC treatment have a negative prognostic value for PSA response and overall survival in these pts. In this study the impact of abiraterone treatment and other subsequent salvage regimens after DC failure was analyzed. Methods: DC failure was defined as disease progression during DC treatment according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 74 consecutive DRPC pts were treated with at least 2 cycles DC until disease progression. At the time of the current analysis 69 pts have progressed and 43 pts received one or more subsequent therapies (1-3). Results: Overall survival (OS) of all 69 pts who have progressed during DC treatment was 8.0 months (CI 95% 3.7, 12.3). 43 pts received subsequent salvage therapies including mitoxantrone-prednisone-etoposide (MPE) (n=10), cabazitaxel (n=13), docetaxel-oxaliplatin (n=8), abiraterone (n=15), enzalutamide (n=5) and doxorubicin-ketokonazol (n=5). OS of these 43 pts was 14.6 months (CI 95% 11.0, 18.2).In pts receiving abiraterone as salvage treatment, OS after DC was 21.8 months versus 11.9 months (CI 95% 9.0, 14.8) in pts receiving other regimens (HR 0.17, CI 95% 0.07, 0.42; p<0.001). Responses of prostate-specific antigen (PSAR; ≥30% and ≥50%) were only frequently observed in pts receiving abiraterone (8/15, 53.3% and 4/15, 26.7%, respectively). Conclusions: Our data demonstrate for the first time that testosterone is an important prognostic factor for PSA response and OS in mDRPC patients receiving DC chemotherapy and that targeting testosterone after DC failure prolongs post-DC survival.
Predictors of clinical metastases and survival among nonmetastatic prostate cancer (PC) patients (pts) treated with androgen-deprivation therapy (ADT) in Sweden.
Authors: Hernandez Rohini Khorana , Mesterton Johan , Banefelt Jonas , Stålhammar Jan , Sobocki Patrik , Persson Bo-Eric , Liede Alexander 
Published: March 2020

e16066 Background: ADT is the standard of care in Sweden for PC pts with signs of recurrence after primary therapy (tx). Studies of predictors of metastasis (mets) and survival have largely focused on pt characteristics at cancer diagnosis. Time-varying factors, such as prostate-specific antigen (PSA) levels, may have greater impact on a pt’s risk of disease progression. This study examines predictors of mets and survival among men with PC treated with ADT. Methods: Using electronic medical records from Swedish urology clinics linked to national registries (Cancer Registry, National Pt Registry, Cause of Death Registry), we identified men with PC and no evidence of mets treated with ≥6 months (mos) ADT (gonadotropin-releasing hormone agonists/antagonists or bilateral orchiectomy) between 2000-2010 with ≥2 PSA values. Men were followed from ADT index date to mets, death, or end of follow-up (12/31/2010). Multivariate competing risks regression analysis was used to estimate hazard ratios (HR) and 95% CIs; predictors and covariates of interest included PC diagnosis year (yr), age, comorbidities, anti-androgen tx, region, and time-varying characteristics (PSA absolute value, PSA doubling time [DT]). Results: Cohort was 446 men with mean follow-up of 3.3 yrs. Most mets were to the bone (7-yr cumulative incidence 25% for bone, 30% for any mets). Median survival was 6 yrs (5.9 mos after bone mets, 6.1 mos after any mets). Higher PSA and shorter PSA DT were strong predictors of all outcomes. In particular, PSA DT ≤ 6 mos was associated with increased risk of bone mets (13.9 [8.0 – 24.1]), any mets (7.9 [4.9 – 12.8]), mortality (5.7 [3.9 – 8.5]), and bone mets-free survival (6.9 [4.7–10.1]) when compared to PSA DT > 6 mos. HRs were adjusted for age, Charlson comorbidity index, anti-androgen tx, and region. Conclusions: PC pts treated with ADT are at significant risk of bone mets, any mets, and death. This study based on real-world data demonstrates the importance of PSA measured after ADT initiation in defining high risk of these outcomes, particularly PSA DT ≤6 mos. PC pts may benefit from new tx to prevent disease progression since survival is short after bone or other mets.
Health-related quality of life after IMRT or IMRT+ HDR brachytherapy for intermediate or high-risk prostate cancer: Five-year results of a prospective trial.
Authors: Guix Benjamin , Lacorte Teresa Maria , Bartrina Jose Maria , Tello Jose Ignacio , Guix Ines , Galdon Guillermo , Espino Marc , Guix Teresa 
Published: March 2020

e16071 Background: To report long term Health Related Quality of Life (HRQoL) in a prospective series of 629 patients with intermediate or high-risk clinically localized prostate cancer treated with either IMRT or IMRT + HDR. Methods: Between December 1999 and December 2010, 629 patients (pts) with PSA›10, Gleason score›6 and/or T2b-T3 N0 M0 prostate cancer entered the study. Pts were prospectively assigned to one of the two treatment groups: 76 Gy HD-3D-IMRT to the prostate in 38 fractions (group 1; 315 patients) or 46 Gy LD-3D-CRT+ 16 Gy HDR-B given in 2 fractions of 8 Gy (group 2, 316 patients), limiting the maximum rectal dose to 85% of the prescribed dose. Both groups were well balanced taking into account patient’s as well as tumors’ characteristics. Toxicities were scored by the EORTC /RTOG morbidity grading scales. Special attention to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels as well as HRQOL was done. Results: All pts completed treatment. None pts included in group 1 or 2 had grade 3 or more rectal toxicity. With a mean follow-up of 96 m, the 8-year free-from-failure survival was 90.7% and 98.3% (p<0.02) in group 1 and 2 respectively; free-from-metastases survival 96.9% and 97.9% (p<0,08)for group 1 and 2; and cause-specific survival 97.4% and 98.3% (p<0.09). HRQoL was evaluated before treatment, at 3 months interval during the first year follow up and in a yearly basis until 10-year. I-PSS and EORTC’s QLQ-C30 with PR-25 were used. I-PSS scores at 1, 3 and 6 months and at 1, 2, 3, 5 and 8 years follow-up were 6.39, 5.00, 2.52, 2.21, 2.35, 3.65 and 1.43 for group 1 pts and 1.50, 1.10, 1.01, 1.05, 0.89, 0.66, 0.67 for group 2 pts. Global HRQoL scores at 1, 3 and 6 months and at 1, 2, 3 and 5 years follow up were 5.56, 5.75, 5.33, 6.00, 5.40, 5.58 and 5.11 for group 1 pts and 5.60, 6.40, 5.78, 5.89, 5.83, 6.37, 6.00 for group 2 pts, being found to be statistically significant at 3 and 5 years follow up (p<0,001 and p<0,024). Conclusions: High-dose 3D-IMRT + HDR brachytherapy was found to be a method of escalating the dose to the prostate that not only increased the chances of cure for patients if not increased their long-term Health Related Quality of Life.
Clinical significance of plasma fibrinogen level in patients with prostate cancer.
Authors: Ma Xiao-Kun , Wen Jing-Yun , Chen Zhan-Hong , Lin Qu , Li Xing , Dong Min , Wei Li , Chen Jie , Wang Tian tian , Ruan Dan-Yun , Lin Ze-Xiao , Wan XiangBo , Wu Xiang-Yuan 
Published: March 2020

e16077 Background: Most of malignant tumor patients have hypercoagulable state with plasma fibrinogen (Fib) levels increased. In this study, we aimed to investigate correlation of plasma Fib with routine prognostic factors of prostate cancer patients, including Gleason score, prostate specific antigen (PSA), TNM 7th Stage. Methods: From January 2007 to December 2012, 107 patients with prostate cancer and 44 cases of benign prostatic hyperplasia (BPH) were included in our study. Automated coagulation analyzer was used to determine the plasma fibrinogen levels. Results: The patients presented a mean age of 70.6 years, a mean PSA level of 28.73 ng/ml, clinically localized prostate cancer in 47 cases, locally advanced condition in 27cases, and distant metastatic disease in 33 cases. The fibrinogen levels were increased in cancer patients compared to that in patients with BPH (P = 0.031). Higher fibrinogen levels related to metastasis, higher TNM stage and increased PSA (p = 0.000, 0.041 and 0.004 respectively). Fib levels were irrelevant to T state, N state, and Gleason score. Conclusions: Prostate cancer patients displayed increased Fib levels. Plasma Fib is significantly increased in patients with higher PSA level,worse TNM stage and distant metastasis. The patients with high Fib might presented relative worse prognosis and should be monitored closely. [Table: see text]
Safety of cabazitaxel in elderly patients with metastatic castrate resistant prostate cancer (mCRPC) previously treated with docetaxel therapy.
Authors: Gernone Angela , Calderoni Giuseppe , Vallarelli Simona , Montagna Elisa , Pagliarulo Arcangelo , Silvestris Francesco 
Published: March 2020

e16081 Background: Cabazitaxel (Cab) is a novel taxane for treatment of mCRPC in progression during or after Docetaxel therapy. However, the management of elderly pts also depends on comorbidities that may impact the performance status and influence the treatment decisions. This study was aimed to assess both activity and safety of Cab in a cohort of ≥ 65 yrs aged patients with mCRPC unresponsive to Docetaxel. Methods: Between 11/2011 and 01/2013, 26 pts with mCRPC relapsing after Docetaxel as first line treatment were enrolled following their comprehensive geriatric assessment for eligibility to the study also extended as EAP. The Cab schedule included 25 mg/m2 every three weeks plus 10 mg Prednisone (P) daily. Comorbidities were assessed using the cumulative illness rating geriatric scale (CIRS-G) with 0-4 score. Median age was 73 yrs (65-89), ECOG PS 0-2, median baseline PSA was 107 ng/ml, whereas comorbidities included pneumonia, arterial hypertension, arrhythmias and diabetes. Pts were managed every 3 months by CT, whereas both response rate (RR) and correlations between comorbidities and toxicity were the endpoints of the study. Results: Pts received the CabP schedule with none dose reduction. Minimal adverse effects were recorded as grade 3-4 anemia whereas no episodes of neutropenic fever were observed. Sexteen/26 pts entered in EAP study. Comorbidities were recorded as GIRS-G1-2 in 17 pts, G3 in 7, and G4 in 2. 9/26 pts received total previous docetaxel dose < 1200 mg/tot and 17/26 pts received ≥ 1200 mg/toto. Among the CabP-treated pts, 3 of them showed partial response with one year of median duration and PSA response ≥ 50%, whereas 8 maintained a stable disease with 9 months of median duration and PSA response < 50%. Conversely, 15 pts underwent progression after 5 months of CabP treatment. Conclusions: Our data suggest that comorbidities in mCRPC ≥ 65 yrs aged pts do not interfere with the toxicity of CabP thus supporting its efficacy and safety in older pts unresponsive to previous Docetaxel therapy. Therefore, CabP does not impact the quality of life and emphasizes a proper disease control (PR+SD) in 11/26 pts.
Cabazitaxel in docetaxel-pretreated metastatic castration resistant prostate cancer (mCRPC): Canadian experience.
Authors: Sridhar Srikala S. , Winquist Eric , Hubay Stacey , Assi Hazem , Berry Scott R. , Stewart John , Levesque Eric , Aucoin Nathalie , Czaykowski Piotr , Saad Fred 
Published: March 2020

e16082 Background: Cabazitaxel/prednisone (CbzP) improves survival in docetaxel resistant mCRPC. Canadian investigators collected safety, QoL and efficacy data in patients (pts) from a global Expanded Access Program. Methods: Following progression on or after docetaxel, all pts received cabazitaxel 25 mg/m² IV q3wkly and prednisone 10 mg daily. Safety and QoL were collected at baseline and at each cycle. Adverse events were graded according to NCI CTCAE v 4.0. Present pain intensity (PPI) and analgesic scores were assessed using the McGill-Melzack questionnaire. QoL was assessed using FACT-P and EQ 5D-3L. PSA was done at the investigator's discretion at each cycle and at the end of treatment. Results: 61 pts were enrolled at 9 centers. Median age was 65 (18% ≥ 75); 92% were ECOG 0/1; 89% had bone metastases and 21% had visceral metastases. Pts had a median of 9 cycles (median cumulative dose 675 mg/m2) of prior docetaxel, and 38% had progressed on or within 3 months of it. Notably 26 pts (43%) had also received and progressed on prior Abiraterone Acetate (AA) given before (5pts), or after docetaxel (21 pts). Half the patients (51%) received >6 cycles of CbzP. Median relative dose intensity was 99%. At cycle 1, 31% received prophylactic G-CSF. Main grade 3+ toxicities were anemia 9.8%, diarrhea 8.2%, fatigue 8.2% and febrile neutropenia 6.6%. Peripheral neuropathy was uncommon (4.9% ; no grade 3+). There was 1 treatment related death (1.6%) due to abdominal sepsis. Compared to baseline, PPI scores improved despite stable analgesic use and were significant at cycles 2, 4, 9 (p<0.05). The FACT-P prostate specific questions showed significant improvements in the first 4 cycles (p<0.05). On the EQ-5D-3L the percentage of patients reporting “no problem” for the pain domain by the last cycle increased. The PSA response rate (≥50% decrease) was 48.7% in 39 evaluable pts and was similar in AA pretreated and non-pretreated pts (47.1% and 50.0% respectively). Conclusions: In routine clinical practice, CbzP treatment was clinically manageable and toxicities were similar to the TROPIC study. PPI and QoL data support a palliative benefit of CbzP. PSA response rate was 48.7% and similar in AA pretreated and non-pretreated pts.
Effect of ET-1, FGF-2, and HGF on intracellular steroidogenesis in prostate cancer cells.
Authors: Vasileiou Chrysoula , Hatzidaki Eleana , Karkabounas Athanasios , Maragkouli Eleni , Vaiou Maria , Dimas Konstantinos , Liakos Panagiotis , Lekka Marilena , Papandreou Christos 
Published: March 2020

e16083 Background: In the prostatic epithelium endothelin-1 (ET-1), fibroblast growth factor-2 (FGF2) and hepatocyte growth factor (HGF) are involved in cell proliferation and inhibition of apoptosis. The aim of this study is to investigate whether neuropeptides such as ET-1 and growth factors such as FGF and HGF may constitute an alternate pathway to intracellular steroidogenesis. Methods: PC3 cells, an androgen independent prostate cancer cell line were cultured in RPMI 1640, fully supplemented with FBS 10% and in serum free conditions. The cells were incubated with ET-1(10nM, 3 hrs incubation), FGF-2 (10 ng/ml, 3 hrs incubation) and HGF(33 ng/ml, 3 hrs incubation), and then progesterone, 17-OH progesterone and aldosterone were measured in cell lysates by LC-MS using LTQ Orbitrap XL MS 2.5.5 SP1 (Thermo-Fisher) equipped with Accela AS 2.2.1, Accela pump. The data were analysed by Xcalibur 2.1.0 Software. Results: In baseline conditions PC3 cells produce no progesterone but high amounts of 17-OH progesterone and small amounts of aldosterone. Upon stimulation with endothelin there was a significant increase in progesterone, significant decrease in 17-OH progesterone and a very significant increase in aldosterone. Similarly stimulation with both HGF and FGF resulted in significant decreases in 17-OH progesterone and increases in aldosterone. Conclusions: Our results imply that in androgen deprivation conditions intracellular steroidogenesis can still take place by stimulation via seven membrane and tyrosine kinase receptors, contributing in part to a steroid dependent phenotype in addition to a steroid independent one, thus implying the potential for new therapeutic interventions.
Efficacy and toxicity of q 2 weeks docetaxel versus weekly versus q 3 weeks in metastatic castration-resistant prostate cancer (CRPC).
Authors: Malhotra Akshiv , Rosenbaum Paula , Poiesz Bernard J. 
Published: March 2020

e16087 Background: Standard treatment for metastatic CRPC is docetaxel 75 mg/m2q3weeks. Methods: We retrospectively studied patients treated with q 1, 2, or 3 weeks docetaxel regimens at 30, 60 and 75 mg/m2, respectively. The choice of regimen and duration of treatment was decided by their oncologist. Patients who had been in a clinical trial previously, or treated with any other chemotherapy before docetaxel were excluded. On this basis 41 patients were studied. Prostate specific antigen (PSA) was used as the primary method to assess response and progression. Response was a decline of >/=50% from baseline value with no clinical or radiographic evidence of disease progression. For patients whose PSA did not decrease, progression was a >/= 25% increase from baseline. If the PSA decreased without reaching response criteria, progression was a >/= 25% increase from nadir. In those who responded, progression was a >/= 50% increase from nadir. The increase had to be at least 5ng/ml. Toxicity was graded on the basis of CTCAE version 4.0. Response rate and toxicity in the 3 arms was compared using a two by two square t-test. Results: There were 12, 14 and 15 patients in the q1w, q2w and q3w arms, respectively. Response rates, mean progression free survival (PFS), median PFS, mean overall survival (OS), median OS, mean cumulative dose (MCD) and toxicity are shown in table 1. Toxicity was similar in the q1w, q2w and q3w arms, except grade 1/2 neuropathy was higher in the q2w arm vs. the q1w arm (p=0.005). Conclusions: The MCD, response rates, PFS and OS in the q1w and q3w arms were similar to previously published reports. Patients in the q2w arm received a statistically significant higher MCD. Our data suggest a better outcome in the q2w arm as compared to the q1w and q3w arms. However, given the small number of patients studied, the results are not statistically significant. Toxicity was similar save for grade1/2 neuropathy. [Table: see text]
Low-dose metronomic oral cyclophosphamide plus prednisone for castration resistant prostate cancer (CRPC): A retrospective study.
Authors: Martinez Lago Nieves , Anido Herranz Urbano , Leon Mateos Luis , Vieito Maria , Varela Ponte Rafael , Aguin Losada Santiago , Brozos Vazquez Elena , Carmona Campos Marta , Rodriguez Lopez Carmela , Cortegoso mosquera Alexandra Sabela , Candamio Folgar Sonia , López López Rafael 
Published: March 2020

e16095 Background: CRPC remains a therapeutic challenge, although in recent years the introduction of new agents has allowed an improvement in overall survival of these patients. In the literature there are few data on the use of cyclophosphamide in this context. The current study was designed to evaluate the efficacy and toxicity of the metronomic oral administration of a combination of cyclophosphamide and prednisone in patients with CRPC, not candidates for docetaxel or after progression to it. Methods: We retrospectively evaluated the medical records of all patients with metastatic CRPC who were treated with prednisone and cyclophosphamide in our institution. Patients had been previously treated with a docetaxel-containing regimen or were not considered candidates for taxanes, because of important comomorbidities or poor Performance Status (PS). Results: Data from 40 patients treated with cyclophosphamide 50 mg/day vo and prednisone 5 mg bid from January 2010 to December 2012 has been analyzed. Baseline characteristics of the patients are listed in the Table. 36 patients were evaluable for efficacy and toxicity. The PSA response rate (RR) was 30%, with partial responses in 7/40 patients. The clinical benefit (stabilization disease + RR) was 52%. Median progression-free survival was 13 weeks (95% CI 13.2 – 14.5). Median overall survival was 46 weeks (95% CI 26.4 – 65.9). The overall 1-year and 2-year survival were 32% and 8 %, respectively. The treatment was safe and well tolerated. Anemia (grade 0-3) was observed in a third of all patients. Conclusions: In this study in patients with a poor prognosis, metronomic oral cyclophosphamide plus prednisone have demonstrated efficacy with excelent tolerance. Oral cyclophosphamide is an interesting alternative to consider in patients non candidates for intravenous chemotherapy. [Table: see text]