bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II clinical study evaluating the efficacy and safety of neoadjuvant and adjuvant sunitinib in previously untreated patients with metastatic renal cell carcinoma (mRCC)(NeoSun).
Authors: Welsh Sarah , Fife Kate , Matakidou Athena , Mullin Jean , Machin Andrea , Qian Wendi , Ingleson Victoria , Dalchau Katy Marie , Whittaker Pamela , Warren Anne , Priest Andrew N , Zaccagna Fulvio , Barrett Tristan , Gallagher Ferdia Aidan , Riddick Antony , Armitage James Neil , Eisen Timothy George Quentin 
Published: September 2018

e16087 Background: Sunitinib improves clinical outcomes in patients (pts) with mRCC. The single arm phase II NeoSun trial was designed to investigate its added value to nephrectomy, and to explore translational biological and imaging biomarkers. Methods: Pts with mRCC, scheduled for nephrectomy, no prior systemic therapy were recruited to receive 50mg OD sunitinib for 12 days, then post-surgery on a 4 week-on, 2 week-off, repeating 6 week cycle until disease progression. Diffusion-weighted, BOLD and dynamic contrast enhanced MR imaging (DW-MRI, DCE-MRI) and research blood sample collection were performed at baseline and end of 12 days. CT Imaging was performed at baseline, pre- and post-surgery, and then every 2 cycles. The primary endpoint was objective response rate (RECIST). Secondary endpoints included changes in diffusion DW-MRI, DCE- MRI of the tumour following 12 days suntinib, overall survival (OS), progression-free survival (PFS), response duration, surgical morbidity/mortality, and toxicity. Results: 14 pts received pre-surgery sunitinib, 71% (10/14) took the planned 12 doses. All 14 underwent total nephrectomy, and 13 recommenced sunitinib post-operatively. The mean number of post-surgery cycles was 11 (range 2 – 22). 58.3% (7/12) of pts achieved confirmed response (95% CI: 27.7 - 84.8%).91.7% (11/12) achieved objective clinical benefit (95% CI: 61.5 - 99.8%). Median OS is 33.7m and median PFS is 15.7m. Amongst those achieving PR/CR, median response duration is 8.7m. No unexpected surgical or sunitinib-related toxicities or complications were observed and the mean number of days from surgery to hospital discharge was 5.9 (range 3.0 – 17.0).There was a trend forOS to be better in pts with high baseline plasma VEGF-A (p = 0.06) or VEGF-C (p = 0.02) expression. A larger % tumour volume reduction after 12 days treatment is correlated with a smaller baseline % necrosis (coefficient = -0.51, p = 0.03). Conclusions: Sunitinib is effective and safe when given before and after nephrectomy to previously untreated pts with mRCC. Neoadjuvant studies such as NeoSun can safely explore translational biological and imaging endpoints. Clinical trial information: 2005-004502-82.
Efficacy of sequencing of cytotoxic and endocrine therapies in veterans with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Lamble Nina Mosallaei , Graff Julie Nicole , Beer Tomasz M. 
Published: September 2018

e16501 Background: The optimal sequencing of therapies in the treatment of mCRPC has not been established. We examined the efficacy of one to two lines of endocrine therapy with chemotherapy sequencied before or in between endocrine therapies versus without chemotherapy. Methods: We prospectively enrolled 103 male veterans from 2013 to 2016 receiving abiraterone or enzalutamide for mCRPC therapy. Participants received usual care. Through chart review, for each line of therapy, we analyzed progression-free survival (PFS), defined as PSA increase 25% and 2ng/mL above nadir and confirmed by a second value, and PSA response rate, defined as a 50% PSA reduction from baseline at treatment initiation, for participants receiving various sequences of endocrine therapies with or without docetaxel chemotherapy. Results: We observed no statistically significant differences between the above measures except for an improvement in PFS when comparing those that received two lines of endocrine therapy without chemotherapy between treatments to those with who received chemotherapy between treatments ( p-value = 0.027, Log-rank test). Conclusions: There were no compelling clinically significant differences noted in PFS or PSA response rate amongst the various sequences of endocrine and cytotoxic therapies. Our results suggest that various sequences of therapy may yield similar results. Larger randomized studies analyzing sequencing of therapies will help determine if cross-resistance arises with use of multiple therapies. [Table: see text]
A first-in-human phase 1 study of proxalutamide (GT0918), a dual MOA androgen receptor blocker in patients with advanced CRPC.
Authors: Zhou Tie , Xu Wei-Dong , Xu Chuang-Liang , Gao Xu , Hou Jian-Guo , Ren Shancheng , Yang Bo , Wei Guolan , Sun Ye , Chen Chunyun , Guo Chuangxing , Tong Youzhi , Zhou Karl , Sun Ying-Hao 
Published: September 2018

e16511 Background: Proxaluatmide is a novel dual MOA androgen receptor (AR) blocker with potent AR antagonist activity and capability to down-regulate AR level. We conducted a first-in-human phase 1 study to investigate safety, tolerability, and pharmacokinetics of GT0918 in patients with advanced CRPC. Methods: All participating patients must be confirmed with advanced CRPC progressed on SoC, PS 0-1, went through 2 periods of time of both single-dose and repeated-dose PK. Patients received GT0918 once orally followed by PK in first 7 days, and then once daily continuously for 28 days for DLT evaluation and repeated-dose PK. PK of drug elimination was done at the end of first cycle (7 days off-treatment). By the end of first 28-day cycle, DLT was evaluated and dose escalation was determined by modified Fibonacci's rule of 3+3 design. If patient tolerated GT0918 well and had no sign of tumor progression, he continued on the study medication thereafter. Results: Ninteen patients were enrolled and 16 patients were treated with GT0918 at five dose levels: 50 mg (n = 2), 100 mg (n = 4), 200 mg (n = 3), 300 mg (n = 3) and 400 mg (n = 4). No DLT was observed. MTD was not reached. GT0918-related adverse events were relatively mild (CTCAE grade 1 or 2), including hypercholesterolemia, peripheral edma, fatigue, flush, constipation and anorexia. PK study showed plasma drug concentrations increased as dose increased from 50mg to 300mg and saturation observed between 300mg and 400mg. Compared single dose (D1) with repeated dose (D35), the elimination half-life (T1/2) were shown 14-35h and 28-51h, respectively. With consideration of overly drug exposure and saturation of oral absorption, 100-400mg were recommended to be the dose range for Phase 2 for further clinical evaluations and dose selection. Clinical activities have been observed in numbers of patients in 100/200/300/400mg dose cohorts. Conclusions: Proxalutamide (GT0918) dosed orally once a day continuously for 12 weeks was generally well tolerated. GT0918 showed promising preliminary anti-tumor activity. Dose range of 100-400mg was recommended for Phase 2 trial and for 24 weeks of treatment.
Enzalutamide (E) versus abiraterone acetate (AA) in the treatment of metastatic, castration-resistant prostate cancer: Results of an indirect comparison with network meta-analysis.
Authors: Cherubini Chiara , Bianchi Emanuela , Drudi Fabrizio , Tamburini Emiliano , Fantini Manuela , Nicoletti Stefania , Stocchi Lucia , Nicolini Mario , Montanari Francesco , Gianni Lorenzo , Tassinari Davide 
Published: September 2018

e16519 Background: To compare efficacy and safety of E and AA in the treatment of metastatic, castration-resistant prostate cancer. Methods: Efficacy and safety of E and AA were compared using the data of the PREVAIL, AFFIRM, COU-AA-302 and COU-AA-301 trials. All the data extracted from the selected trials were reported ad Hazard Ratio (HR) or Odds Ratio (OR). Overall survival was assumed as index of efficacy, and was the primary end point of our analysis, all the side effects, grade III-IV side effects, serious side effects, side effects leading to treatment discontinuation or death were assumed as indexes of safety and were the secondary end points of our analysis. Overall survival was assessed both in the entire population and in the subgroups of patients chemotherapy-naïve or docetaxel-resistant. An alpha error of 5% was assumed as index of statistical significance. Results: The outcome of 5191 patients were reviewed. 1671 patients had been treated with E, 1339 with AA and 2181 with placebo. Comparing E vs AA no differences were observed for overall survival in the entire population (HR = 0.955, IC95% = 0.796-1.144, p = 0.616), overall survival in chemotherapy-naïve patients (HR = 0.947, IC95% = 0.723-1.24, p = 0.692), overall survival in docetaxel-resistant patients (HR = 0.961, IC95% = 0.753-1.228, p = 0.75), all side effects (OR = 0.414, IC95% = 0.054-3.196, p = 0.463), grade III-IV side effects (OR = 1.36, IC95% = 0.253-7.318, p = 0.72), serious side effects (OR = 0.742, IC95% = 0.137-4.006, p = 0.729), side effects leading to treatment discontinuation (OR = 0.743, IC95% = 0.132-4.193, p = 0.736), and side effects leading to death (OR = 0.572, IC95% = 0.089-3.657, p = 0.556). Conclusions: Although E and AA differ for pharmaceutical structure and mechanism of action, they seem to be comparable both for indication (pre- or post-docetaxel treatment in patients with metastatic, castration-resistant prostate cancer), and for efficacy or safety (in chemotherapy-naïve and docetaxel-resistant patients). It follows that compliance, patients characteristics and costs can play a role in the decision making process of clinical practice.
New treatment for advanced and hormone refractory prostate cancer (HRPC) with an oral cholesterol derivative (hydroxysterol 24-ethyl-cholestane- 3β,5α,6α-triol).
Authors: Habib Nabil , Hage George , Daaboul Hamid Elia , Jabbour Abdo Elias , Zeitouni Hind , Khalife Ryiad 
Published: September 2018

e16531 Background: Hydroxysterols and oxysterols are oxygenated derivatives of cholesterol. They are involved in the regulation of some aspects of neoplastic cell growth and proliferation, as demonstrated in vitro in a variety of human cancer cells including prostate cancer cells.These effects can be dependent on the activation of the oxysterol-binding liver X receptors (LXRs). LNCaP prostate tumor cells stimulated with synthetic LXR agonists showed G1 to S-phase cell cycle arrest through the suppression of Skp2.Prostate cancer is the most frequent cancer in men and most patients become resistant to upfront treatments with hormones. At advanced stages most refractory patients are symptomatic and their life expectancy is limited. (24-ethyl-cholestane- 3β,5α,6α-triol) is a new hydroxysterol developed by us. It is the first oxysterol to be tested in the clinic. It is also one of the safest in this class of compounds. Methods: We have treated with this new drug 14 patients suffering from advanced and hormone-refractory prostate cancer (HRPC). Their median age was 73 (60-88). Seven with a Gleason 7, 5 with a Gleason 8 and 2 with a Gleason 9. Eleven had stage IV disease, Eight with bone metastasis, 4 with advanced loco-regional disease and 2 with visceral metastasis. Ten patients were symptomatic. Four patients had received also 1 line of chemotherapy and 2 others received 2 lines of chemo. Four patients were also previously treated with radiotherapy. Patients received daily 10 mg/Kg of oral (24-ethyl-cholestane- 3β,5α,6α-triol) divided into 3 equal doses, until disease progression. Results: Ten patients experienced either a biological or a radiological partial response (PR), Two patients had a stable disease (NC) and two patients had a disease progression (PD). The median duration of response was 2 years. Patients did not report any side-effect from treatment. Eighty percent of symptomatic patients had a remarkable symptom control. Conclusions: These encouraging results make this new and safe drug a good candidate for further clinical trials either alone or in combination with other drugs in the treatment of HRPC.
Costs of pre-hospice care among metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone + prednisone (ABI) and enzalutamide (ENZ).
Authors: Li Sophia S , Engel-Nitz Nicole , Blauer-Peterson Cori , Behl Ajay S. , Dawson Nancy Ann 
Published: September 2018

e16534 Background: mCRPC patients are likely to receive oral therapies such as ABI or ENZ prior to hospice care. Payers and clinicians perceive hospice care as improving the quality of life for advanced prostate cancer patients dying of cancer, but literature suggests that it may be underutilized. A previous study found a longer time to starting hospice for patients initiated on ABI (vs. ENZ) with no significant difference in time spent in hospice. Understanding the active-treatment period prior to hospice may shed light on the overall burden of treatment without discounting the benefits of hospice. This study examined total pre-hospice per patient per month (PPPM) costs among mCRPC patients who utilized hospice care and treated with ABI or ENZ. Methods: A retrospective study of a large national health claims database identified patients initiated on ABI or ENZ from 09/2012 to 06/2015. Patients included had: ≥1 claim with a prostate cancer diagnosis (ICD-9-CM 185.xx) from 6 mo. pre- to 30 days post-index; ≥6 mo. pre- and ≥3 mo. post-index health plan enrollment. Index was date initiated on first oral therapy (ABI/ENZ). The subset of patients who entered hospice care were identified. Descriptive analyses assessed total PPPM costs (pharmacy, ambulatory, ER, inpatient, other medical costs) for subset of pre-hospice patients and all patients. Generalized linear model (GLM) assessed adjusted pre-hospice costs. Since the GLM used a log-link function with cost as a dependent variable, results are interpreted as a ratio of costs. Results: Among 1,516 mCRPC patients, 213 had utilized hospice care (ABI: 161, ENZ: 52). Total pre-hospice PPPM cost was greater for patients initiated on ENZ (ENZ = $19,485 ABI = $13,252; p = 0.048). Adjusted analysis found a 25.8% greater PPPM cost for those patients (Cost Ratio = 1.26, p = 0.038). Among all 1,516 patients, total all-cause PPPM cost was higher in ENZ but not statistically significant (ENZ = $11,268 ABI = $10,520; p = 0.090). Total prostate cancer related PPPM cost was statistically significant (ENZ = $10,327 ABI = $9,477, p = 0.038). Conclusions: Total pre-hospice PPPM cost is 26% lower for mCRPC patients initiated on ABI vs. ENZ.
Predictors of radiologic progression free survival (rPFS) during abiraterone acetate (AA) treatment in a randomized phase II study of AA maintenance in combination with docetaxel (D) after disease progression to AA in metastatic castration resistant prostate cancer (mCRPC): ABIDO-SOGUG trial.
Authors: Castellano Daniel , Méndez-Vidal María José , Puente Javier , Sáez M Isabel , Font Pous Albert , Duran Ignacio , Santander Carmen , Sanchez-Hernandez Alfredo , Arranz Arija Jose Angel , Alonso Teresa , Mellado Begoña , Lázaro Quintela Martin , Gonzalez del Alba Aranzazu , Esteban Emilio , Maroto Pablo , Cassinello Javier , Climent Miguel Ángel 
Published: September 2018

e16536 Background: AA improves OS and rPFS in asymptomatic/minimally symptomatic mCRPC patients. D is currently one of the standard treatments after progression to AA. However, the value of maintaining AA along with D despite progression to AA has not been tested. ABIDO trial aims to evaluate efficacy and safety of AA + D maintenance after disease progression to first line AA in mCRPC. Clinicopathologic features associated with rPFS during first line AA are presented. Methods: ABIDO trial is a randomized, phase II, open-label study with two stages. In stage I pts receive AA (1000 mg + prednisone (P) 10 mg qd) until progressive disease. In the stage II pts will be randomized to receive three-weekly D 75 mg/m2plus P 10 mg/d with (arm A) or without (arm B) AA 1000 mg/d. Pts had no visceral metastases, ECOG PS 0-1, and adequate organ functions. Clinicopathological predictors for rPFS to first line AA were estimated using the Kaplan-Meier method and independent associations were evaluated using Cox regression models. Results: 143 pts were included. Analyzed variables were: median age was 70y, 60% of pts had ECOG 0, 84% bone metastases (18% > 4), 42% BPI score 2-3, 53% Gleason > = 8, 30% PSA > 80 ng/mL, 38% node involvement and 11% had at least one lymph node > = 3 cm; 53% of pts achieved 4 weeks PSA reduction > 50%.Median rPFS was 18 months. Univariate analysis identified as significant variables: PSA, BPI, Gleason, node involvement, 4 weeks PSA reduction > 50%, and total volume of lymph node metastasis. On multivariate analysis, BPI (0-1 vs 2-3) (hazard ratio [HR] 1.81; p = 0.039), Gleason ( < 8 vs > = 8) (HR 2.51; p = 0.005), node involvement (no nodes, nodes < 3 cm and at least 1 node > = 3 cm (HR 2.8; p = 0.001 and 3.57; p = 0.009) and PSA reduction > 50% (HR 3.06; p < 0.001) were independently associated with rPFS. Median rPFS was superior in pts with 3 or more good prognostic factors (14m vs not reached; p < 0.001). Conclusions: BPI, Gleason, node involvement and 4-week PSA response were identified as independent prognostic factors for rPFS in first line AA treated patients. Clinical trial information: NCT02036060.
Insurance status and patterns of late diagnosis and cancer treatment: A population-based study.
Authors: Lu-Yao Grace L. , He Jianming , Giri Veda N. , Klassen Ann 
Published: September 2018

e16553 Background: This population-based study assesses the relationship between insurance status and patterns of prostate cancer diagnosis and treatment among men under age 65. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 114,871 prostate cancer patients who were diagnosed before 65 between January 2007 and December 2013. Insurance type was classified as uninsured (3.1%), Medicaid (5.1%) and other including private insurance and coverage from the military or Veterans Affairs (91.8%). We used logistic regression model to quantify the relative risk of being diagnosed with metastasis or regional disease, and the relative likelihood of receiving radical prostatectomy or radiotherapy among those with localized cancer adjusted by, age, race, marital status, region, and diagnosis period. Results: Medicaid or uninsured patients are more likely to have late diagnosis (diagnosed with positive lymph node or metastasis) than patients with non-Medicaid insurance (Table 1). Among men diagnosed with localized prostate cancer, Medicaid and uninsured patients are less likely to receive prostatectomy. Medicaid patients are more likely to have radiotherapy than un-insured (see table). Conclusions: Compared with patients with non-Medicaid insurance, Medicaid and uninsured patients are more likely have late diagnosis and less likely to have radical prostatectomy for localized cancer, after accounting for differences in age, race, marital status, region, and diagnosis period. [Table: see text]
Utility of a novel biopsy instrument with long side-notch needle in the selection of patients for active surveillance.
Authors: Kanao Kent , Kajikawa Keishi , Kobayashi Ikuo , Muramatsu Hiroyuki , Morinaga Shingo , Nishikawa Genya , Kato Yoshiharu , Watanabe Masahito , Nakamura Kogenta , Sumitomo Makoto 
Published: September 2018

e16581 Background: Active surveillance (AS) is now an accepted strategy for men with low-risk prostate cancer (PCa). A critical factor for successful AS is the best possible patient selection. We recently develop a novel 18-G biopsy instrument based on an existing instrument, by extending the side-notch length from 19 to 25 mm and the stroke length from 22 to 28 mm, to take a longer tissue core and to reach the anterior portion of the prostate.In this study, we evaluated utility of the novel biopsy instrument in the selection of patients for AS. Methods: A total of 167 PCa patients diagnosed with the long-notch needle (n = 62; long-notch group) or normal-notch needle (n = 105; normal-notch group), who subsequently underwent prostatectomy, were retrospectively analyzed. All patients were diagnosed with 12 transrectal ultrasound-guided standard cores.The sampled core length, correlation between total tumor length in biopsy specimens, and total tumor volume in prostatectomy specimens were compared between the two groups. Gleason score (GS) upgrading was also compared. Prostatectomy specimens of patients who met the criteria of the PRIAS study were compared for the two groups. Results: The mean length of tissue taken with the long-notch needle was significantly longer than that taken with the normal-notch needle (16.3 vs. 22.4 mm, p < 0.001). The correlation coefficient between total tumor length in biopsy specimens and total tumor volume in prostatectomy specimens of the long-notch group was higher (r = 0.701) than that in the normal-notch group (r = 0.611). GS upgrading in the long-notch group was significantly lower than that in the normal-notch group (25.8 vs. 41.0%, p = 0.0479).Only 1 patient with tumor volume > 0.5 cc and GS 4+3 or more was included among the 5 who met the criteria of the PRIAS study in the long-notch group, while 6 patients were included among the 10 who met the criteria in the normal-notch group. Conclusions: We developed a novel biopsy instrument with a 25 mm side-notch for longer tissue samples, increased correlation between tumor volume in biopsy and prostatectomy specimens, and decreased GS upgrading. These results suggested the utility of the long-notch needle in the selection of patients for AS.
Phase II study of perioperative combination chemotherapy with triweekly carboplatin and weekly dose dense paclitaxel and radical hysterectomy for locally advanced cervical cancer (SGSG-016 study).
Authors: Nagao Shoji , Kogiku Ai , Nonaka Michiko , Shiroyama Yuko , Oishi Tetsuro , Yamaguchi Satoshi , Takehara Kazuhiro , Shimada Muneaki , Kigawa Junzo 
Published: September 2018

e17022 Background: The primary objective of this study was to assess efficacy and safety of triweekly carboplatin plus weekly dose dense paclitaxel (ddTC therapy) before and after radical hysterectomy without radiotherapy (RH) for women with locally advanced cervical cancer. Methods: Patients with FIGO stage IB2, IIA2, or IIB cervical cancer received 3 cycles of carboplatin at an area under the curve of 6 on day 1 and paclitaxel at 80mg/m2on day 1, 8, and 15 every 21 days followed by RH. Patients with one or more high-risk factors for recurrence including lymph vascular invasion, parametrial invasion, lymph node matastasis, or positive margin received additional 3 cycles of ddTC therapy after RH. Results: Between September 2014 and July 2016, 50 women including 13 with FIGO stage Ib2, 5 with stage IIa2, and 32 with stage IIb were enrolled in this study. There were 37 squamous cell carcinoma, 10 adenocarcinoma, 2 adenosquamous carcinoma, and 1 large cell neuroendocrine carcinoma. Median age was 46 years (range 30-78). Forty-three women (86%) completed planed 3 cycled of chemotherapy before surgery. The overall response rate was 92% (18 complete response, 28 partial response, 3 stable disease, 1 progressive disease). Forty-nine patients (98%) completed planed radical hystsrectomy, but a patient with invasion to bladder musculature received concurrent radiation therapy instead of surgery. Eleven patients (22%; 10 with SCC, 1 with large cell neuroendocrine carcinoma) achieved pathological complete response. Eleven other patients with one or more high-risk factors received 3 cycles of ddTC therapy after surgery. Grade 3/4 hematological toxicities included neutrocytopenia (58%), thrombocytopenia (2%) and anemia (24%). One patients experienced neutropenic fever. Grade 3/4 non-hematological toxicities were observed in 4 patients (1, grade 3 nausea; 1, grade3 carboplatin allergy; 1, grade 3 paclitaxel allergy; 1 grade 3 elevetaed liver enzyme). Conclusions: Administration of ddTC therapy before and after RH has good efficacy and acceptable toxicity in women with locally advanced cervical cancer. Clinical trial information: UMIN000024136.