tbuckley/cabot-search huggingface dataset:
A clinical trial for the safety and immunogenicity of a DNA-based immunotherapy in men with biochemically (PSA) relapsed prostate cancer.
Authors: Neal D. Shore, Elisabeth I. Heath, Luke T. Nordquist, Heather H. Cheng, Kamalnayan Bhatt, Nicholas Carroll, Kimberly Kraynyak, Jessica Lee, Jan Van Tornout, Brian Sacchetta, Scott T. Tagawa, Rahul Atul Parikh, Ronald F. Tutrone, Jorge A. Garcia, Young E. Whang, Jianqing Lin, William Kevin Kelly, Ildiko Csiki, Mark L. Bagarazzi
Journal: Journal of Clinical Oncology (2017)

80 Background: Introducing amino acid sequence changes in highly expressed self-antigens for androgen sensitive prostate cancer pts might be sufficient to break tolerance, thus a DNA vaccine was developed using SynCon PSA and PSMA (INO-5150) that share 96.8 and 91.6% sequence identities to these native antigens, respectively. Administration of these antigens to prostate cancer pts along with plasmid encoded adjuvant IL-12 (INO-9012) via electroporation (EP) using the CELLECTRA5P device is postulated to break tolerance, resulting in an antigen-specific immune response which could lead to stabilization of disease progression. Methods: This Phase I, open-label, multicenter study included prostate cancer pts post-definitive therapy with a rising PSA ≥ 1.0 ng/ml after surgery, or ≥ 2.0 ng/ml above nadir after RT and PSA doubling time &gt; 3 months, testosterone &gt; 150 ng/dL and no evidence of metastasis within 12 months. INO-5150 with or without INO-9012 was administered IM followed by EP in 4 arms: low (2 mg) or high dose (8.5 mg) INO-5150 alone or with 1 mg INO-9012 on Day 0 and at week 3, 12, and 24 in 60 planned pts (15 pts/arm). DLT assessments were performed after dosing of the first 3 pts of each arm at Week 4. Results: Enrollment is complete in all 4 arms and at data cut-off (10Oct16), 62 enrolled pts received at least one, 60 pts received 3 and about half, 28 pts (10 in arm A, 8 in B, 7 in C, and 3 in D) received all 4 vaccinations. Safety: there were no DLTs noted. Four pts had five Grade 3 SAEs noted as pre-syncope, cardiac disorder, hospitalization for fall, ALT and AST elevation. No Grade 4-5 AEs were noted. Grade 1-3 treatment-emergent AEs occurred in 50 (81%) pts: 12 (75%) in arm A, 13 (87%) B, 13 (87%) C, and 12 (75%) in D. The most common AEs were injection site pain (24/39%), erythema (13/21%), swelling (12/19%), bruising (10/16%), hyperglycemia (8/13%) and fatigue (6/10%), all Grade 1-2. Assessments of immunological response, PSA kinetics and correlation with clinical outcome are ongoing and will be presented. Conclusions: INO-5150 (+) or (-) INO-9012 is generally safe and well-tolerable at all 4 dose levels in a biochemically relapsed prostate cancer patient population. Clinical trial information: NCT02514213.
Sodium Intake Among Persons Aged ≥2 Years — United States, 2013–2014
Authors: Zerleen S. Quader, Lixia Zhao, Cathleen Gillespie, Mary E. Cogswell, Ana L. Terry, Alanna Moshfegh, Donna Rhodes
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

High sodium consumption can increase hypertension, a major risk factor for cardiovascular diseases (1). Reducing sodium intake can lower blood pressure, and sodium reduction in the U.S. population of 40% over 10 years might save at least 280,000 lives (2). Average sodium intake in the United States remains in excess of Healthy People 2020 objectives,* and monitoring sources of sodium in the U.S. population can help focus sodium reduction measures (3,4). Data from 2013-2014 What We Eat in America (WWEIA), the dietary intake portion of the National Health and Nutrition Examination Survey (NHANES),† were analyzed to determine the ranked percentage sodium contribution of selected food categories and sources of sodium intake from all reported foods and beverages, both overall and by demographic subgroups. These latest data include updated food codes and separate estimates for intake among non-Hispanic Asians.§ In 2013-2014, 70% of dietary sodium consumed by persons in the United States came from 25 food categories; breads were the top contributor, accounting for 6% of sodium consumed. A majority of sodium consumed was from food obtained at stores; however, sodium density (mg/1,000 kcal) was highest in food obtained at restaurants. A variety of commonly consumed foods contributes to U.S. sodium intake, emphasizing the importance of sodium reduction across the food supply (4).
More stereotypes, please! The limits of ‘theory of mind’ and the need for further studies on the complexity of real world social interactions
Authors: Kristin Andrews
Journal: Behavioral and Brain Sciences (2017)

I suggest that the Stereotype Rationality Hypothesis (Jussim 2012) is only partially right. I agree it is rational to rely on stereotypes, but in the complexity of real world social interactions, most of our individuating information invokes additional stereotypes. Despite assumptions to the contrary, there is reason to think theory of mind is not accurate, and social psychology's denial of stereotype accuracy led us toward mindreading/theory of mind - a less accurate account of how we understand other people.
Enhanced therapeutic efficacy of combined use of sorafenib and transcatheter arterial chemoembolization for treatment of advanced hepatocellular carcinoma.
Authors: Lin Zhou, Jin Li, Ding-Lun Ai, Junliang Fu, Xiao-Ming Peng, Lin-Zhi Zhang, Yun Zhao, Jing-Yan Wang, Qiang Yu, Chun-Zi Liu, Wei Ma, Hua-Ming Wang
Journal: Journal of Clinical Oncology (2014)

e15120 Background: Clinical trials suggest that combining therapy of transcatheter arterial chemoembolization (TACE) with sorafenib for the treatment of patients with advanced hepatocellular carcinoma (HCC) shows a superior safety and tolerability profile. The present study aimed to retrospectively analyze the utility and prognostic factors of this combined therapy in advanced HCC patients. Methods: Patients with advanced HCC, treated by TACE and sorafenib subsequently, between February 2010 and September 2012 in our hospital, were retrospectively analyzed. After sorafenib treatment for 12 weeks, abdominal enhanced CT or MRI was used to evaluate short-term outcomes and clinical benefit rate (CBR). Overall survival (OS) and adverse events (AEs) were recorded during follow-up. Univariate and multivariate analyses were used to identify relationships between baseline characteristics and OS. Results: A group of 51 patients with advanced HCC were included. Common AEs for sorafenib were hand-foot skin reaction, alopecia, diarrhea, anorexia, and fatigue. The CBR was 64% and the median survival time was 7.5 months. Median survival of patients with and without portal vein tumor thrombi (PVTT) was 6.0 months and 10.3 months (P<0.001), respectively. Median survival of patients with cholinesterase (ChE) ≥5000 U/L and ChE <5000 U/L was 10.6 months and 6.1 months (P<0.001), respectively. Multivariate analysis identified the presence of PVTT and low ChE level as independent negative predictors of survival. Conclusions: Combining therapy of sorafenib and TACE was safe and effective for advanced HCC patients. PVTT and ChE level are independent predictors of prognosis following use of this combination treatment.
A phase I study of mFOLFOX6 and ADI-PEG-20 in patients (pts) with advanced hepatocellular carcinoma (HCC) and other gastrointestinal (GI) malignancies.
Authors: James J. Harding, Maeve Aine Lowery, Khrystyna Uhlitskykh, Peter Justin Wan, Casey R Hamilton, Adalberto Barba, Kay Chia-Wei Liu, Amanda Johnston, John S. Bomalaski, Eileen Mary O'Reilly, Leonard Saltz, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2017)

384 Background: ADI-PEG-20 (pegylated arginine deiminase), an arginine degrading enzyme, and FOLFOX each exhibit clinical activity in a HCC pt subset. Preclinical data indicate that arginine depletion interferes with folate and pyrimidine metabolism as well as DNA damage repair pathways, suggesting a role for pairing AGI-PEG-20 with cytotoxic chemotherapy. Methods: This is a single center phase 1 trial of mFOLFOX-6 and ADI-PEG-20 in treatment-refractory advanced GI tumors to assess safety and tolerability, and to identify the recommended phase 2 dose (R2PD). mFOLFOX6 was administered intravenously biweekly at standard fixed doses and ADI-PEG-20 intramuscularly weekly at 18 or 36 mg/m2. Toxicity was assessed by CTCAE v4.03 and efficacy by RECIST v1.1. A HCC RP2D expansion was completed to explore efficacy. Serum arginine, citrulline, and anti-ADI-PEG-20 antibodies were monitored every other week. Results: 17 pts were treated—7 pts with GI tumors in dose escalation and 10 HCC pts in RP2D dose expansion. Histologies included HCC (13), pancreatic (3) and fibrolamellar carcinoma (1). All HCC pts had Child-Pugh A liver function and had progressed on sorafenib. Treatment-related grade ≥ 3 laboratory adverse events (AEs) occurred in 47% of pts, including neutropenia (4), thrombocytopenia (3), anemia (2), lymphocytopenia (2) and hyponatremia (1). Treatment-related grade ≥ 3 clinical AEs occurred in 2 pts, notably grade 3 fatigue and a grade 3 cardiac event not otherwise specified. No dose limiting toxicities, treatment-related deaths, or cases of hepatic failure were observed. Efficacy data for the 13 HCC pts revealed 3 (23%) PR, 6 (46%) SD, 3 PD and 1 NE. Arginine levels were depleted with therapy (mean ± SEM: baseline 85.3 ± 13.0 uM, 8 wks 4 ± 3.0 uM, 16 wk 1.1 ± 0.8uM). Anti-ADI-PEG-20 antibodies were not detected at 8 weeks (mean ± SEM: baseline 0.7 ± 0.5, 8 wks 1.5 ± 1). Conclusions: Concurrent mFOLFOX6 plus ADI-PEG-20 intramuscularly at 36 mg/m2 weekly shows an acceptable safety profile with rapid and durable reduction in serum arginine. Further evaluation of this combination is warranted in advanced HCC pts. Clinical trial information: NCT02102022.
Comparison of outcomes of phase II trials (P2Ts) and subsequent randomized control trials (RCTs) using identical therapeutic regimens
Authors: M. I. Zia, L. L. Siu, G. R. Pond, E. X. Chen
Journal: Journal of Clinical Oncology (2004)

6000 Background: RCTs are cornerstones of evidence-based clinical oncology practice. RCTs are often based on promising results from P2Ts. However, it is not clear whether these results translate into positive RCTs. Methods: We searched for all RCTs of chemotherapy or combined chemotherapy and radiation therapy in solid malignancies published in the English language literature from July 1998 to June 2003. RCTs of neoadjuvant or adjuvant therapy were excluded. Eligible RCTs were reviewed to identify preceding P2Ts. To be included in the analysis, P2Ts and RCTs must have used identical therapeutic regimens in same patient populations. RCTs were considered to be positive if the experimental regimen was significantly better than the control in terms of primary endpoints. Response rates from both P2Ts and RCTs were retrieved. The following variables were also collected from P2Ts: number of patients, whether P2Ts were randomized and/or multi-centered, and the impact factor of the journal in which a P2T was published. Logistic regressions were performed to evaluate influences of these variables on outcomes of subsequent RCTs. Results: Of 181 RCTs identified, 47 used same therapeutic regimens as those in 59 preceding P2Ts. Ten (21.3%) of 47 RCTs are considered positive RCTs. Response rates were at least equal to those in P2Ts in only 9 (19.1%) RCTs. The mean difference in response rates between P2Ts and RCTs was 13% (absolute difference, range: 0 - 37.8%). The only statistically significant predictor of a positive RCT is the number of patients entered in preceding P2Ts. For every 10-patient increment in the size of a P2T, the odds of observing a positive RCT increases by 1.22 times (p = 0.042). Conclusions: Promising results from P2Ts frequently do not translate into positive RCTs. Response rates in most RCTs are lower than those in preceding P2Ts. The only significant predictor of a positive RCT is the number of patients in preceding P2Ts. No significant financial relationships to disclose.
Preclinical development of an interleukin-11 receptor-targeted pro-apoptotic peptide against advanced prostate cancer
Authors: A. J. Zurita, A. Hajitou, M. Cardó-Vila, P. Troncoso, C. J. Logothetis, R. Pasqualini, W. Arap
Journal: Journal of Clinical Oncology (2004)

3190 Background: Direct screening of combinatorial peptide libraries in patients allows the identification of ligands that target biochemical differences in the endothelium of blood vessels. In a screening performed on a patient, we selected and isolated a mimic motif of interleukin 11 (IL-11) from prostate biopsies after an intravenous administration of a phage display peptide library. We also demonstrated that the IL-11 phage mimic bound specifically to a corresponding IL-11 receptor (IL-11Rα). More recently we showed that IL-11Rα is a potential target for intervention in human prostate cancer (PCa) through morphologic and functional analyses (Zurita et al., Cancer Res 2004, in press). We observed stage-specific up-regulation of IL-11Rα during disease progression, particularly in androgen-independent and metastatic PCa and their associated blood vessels. Moreover, a pro-apoptotic peptide was specifically targeted and internalized through IL-11Rα in PCa cell lines. Here we evaluate antitumor efficacy, selectivity of action, and host toxicity in preclinical animal models of human PCa. Methods: We are currently performing systemic efficacy studies in nude mice PCa xenograft models, and dose range-finding studies to establish a maximally tolerated dose in mice. Results: Our preliminary data show promising results against PCa xenografts in nude mice. Conclusions: An IL-11Rα-targeted, chimeric pro-apoptotic peptide, is a candidate for translation into clinical applications. No significant financial relationships to disclose.
Initial English translation and validation of a symptom-specific quality of life (QOL) module for acute myeloid leukemia (AML)
Authors: S. M. Alibhai, A. Schumacher, T. Kuchler, H. Kermalli, A. Schattner, V. Gupta, J. Brandwein, M. D. Minden, A. Schuh, R. W. Wells
Journal: Journal of Clinical Oncology (2004)

8183 Background: QOL is becoming increasingly important in oncology and is usually measured using general cancer scales and symptom-specific scales. AML is an aggressive hematological tumor that affects primarily older adults and often responds poorly to standard treatment. Understanding QOL will assist in treatment decision-making, symptom palliation, and evaluation of new biologic agents. Yet there is no validated English-language symptom module for use in AML. Methods: In this pilot study, we set out to translate and perform English-language validation of an existing German symptom-specific module for AML designed by Schumacher and Kuchler for use with the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 (Leukemia 1998; 12:586). Forward-backward translation of the 20-item module (7 subscales) was performed. Face and content validation of the English module were assessed by a panel of hematologists and QOL researchers. The module was then administered along with the QLQ-C30 to 14 English-speaking patients aged 60 or older with newly diagnosed AML at baseline and at 1 and 4 months. Semi-structured interviews were conducted with patients to assess clarity and comprehensiveness. Results: 10 men and 4 women with a mean age of 73 years completed the instruments on up to 3 occasions. Completion rates were 100%. The module was completed in a mean of 5 minutes (range 3–8). Item analysis indicated adequate scaling for all items. One question required minor rewording. No additional items were suggested by patients for inclusion. There were moderate correlations between global QOL on the QLQ-C30 and both general symptoms and diagnosis-specific symptoms in the symptom module. Pain subscales in the symptom module correlated well with the QLQ-C30 pain subscale. Conclusion: Administration of a symptom-specific QOL module is feasible in older patients with AML. The module has face and content validity, preliminary construct validity, and can be administered in a short time frame. Further testing is required to examine reliability, construct validity, and responsiveness. No significant financial relationships to disclose.
In-patient supportive care unit in oncology: A 3-year assessment (2011-2013).
Authors: Maria Kfoury, Pauline Leroy, Stephane Hans, Christian Herve, Daniel Brasnu, Stephane Oudard, Clarisse Sauvajot, Christophe Aubaret, Ludovic Tripault, Anne Guillou, Florian Scotte
Journal: Journal of Clinical Oncology (2014)

e20708 Background: An in-patient unit for supportive care in oncology (USSO) was created in 2011 at the Georges Pompidou European Hospital. Its primary objective was to improve patient care management and complications during their cancer treatment. A yearly evaluation was conducted to monitor the unit’s activity. Methods: An observational study was performed in the 4-bed unit from January 1 - December 31, 2013. Results: A total of 244 patients were included in the study (158 in 2011 versus 192 in 2012). In 2013, 67.6% of patients came directly from home, which resulted in 6.5% emergency admissions. The predominant diseases observed were head and neck cancer 37.7% and lung cancer 24.1%. The main reasons for hospitalization were bad performance status 30.3%, pain 13.5%, invasive procedures 12.7%, and nutritional disorders 9.1%. In USSO, an interdisciplinary approach remains the cornerstone of treatment with a daily collaboration of dieticians, psychologists, physiotherapists, and the palliative care team. Based on this policy, the patients average length of stay was reduced to 8.3 days for an occupancy rate of 100%. Finally, 61% of the patients were discharged home. With the help of a social worker, 9% of the patients were transferred to a recovery unit and 12.7% to a palliative care unit (total 9% deaths recorded). Conclusions: With the opening of the in-patient USSO, and the development of its interdisciplinary strategy, most of the patients were able to recover faster. By anticipating admissions at an early stage of the disease or treatment complications, we greatly amended patient management. These positive results enabled us to increase USSO capacity from 4 to 8 beds, which not only improved the supportive care organization but also the patient’s quality of life. 2011 2012 2013 Total Number of stays 158 192 244 584 Home admissions (%) 59.4 64 67.6 Emergency admissions (%) 17.7 8.3 6.5 Home discharge (%) 51.8 60 61
Complications of hyperglycemia in phase 1 trials targeting the PI3K-akt-mTOR (PAM) pathway.
Authors: Elena Geuna, Desamparados Roda, Saeed Rafii, Begona Jimenez, Marta Capelan, Karim Rihawi, Timothy Anthony Yap, Stanley B. Kaye, Johann Sebastian De Bono, L Rhoda Molife, Udai Banerji
Journal: Journal of Clinical Oncology (2014)

2612 Background: PAM inhibitors (PAMi) are targeted agents increasingly being used as single agents or in combinations to treat metastatic cancer. Hyperglycemia has often been reported as an on-target toxicity of agents inhibiting this pathway and will become increasingly important with their use in larger number of patients (pts). We aimed to compare the incidence and degree of hyperglycemia across a range of PAMi phase I clinical trials. Methods: Retrospective case-control study of 510 pts with advanced solid tumours treated on 28 different phase 1 clinical trials at the Royal Marsden Hospital, UK, between June 2008 and May 2013. Data were collected on pt treatment and tumor characteristics, baseline and highest blood sugar levels during the trial. Results: 400 pts were treated in 18 trials with PAMi (82 pts with PI3Ki, 139 with mTORi, 150 with AKTi and 29 with PI3K/mTORi). A control group of 110 pts treated in 10 trials of targeted agents not targeting the PAM pathway were randomly selected. Baseline characteristics were well balanced between both study groups. There was no difference in the incidence of all grade hyperglycemia in the PAMi and control group, 347/400 (86.7%) and 89/110 (80.9%), OR 1,55 (95% CI 0.89-2,69 p=0.124). Importantly there was increased grade 3-4 hyperglycemia in pts in PAMi versus controls respectively, (28/400 vs 0/110, p = 0.005). Within the PAMi treated group the incidence of grade 3-4 hyperglycemia was 1.2%/11.3%/ 2.9%/20% in PI3K, AKT, m-TOR and PI3K/mTOR inhibitors, respectively and these differences were statistically significant (p = 0.001). In the PAMi group the study drug was stopped in 9 pts (2.3%) due to hyperglycemia. Only 27 pts (7%) required treatment for hyperglycemia; n=23 (6%) metformin and n=4 (1%) insulin. No pts developed severe metabolic complications, e.g. diabetic ketoacidosis or hyperosmolar hyperglycemic state. Conclusions: PAMi are associated with a significantly increased risk of high-grade hyperglycemia, compared with controls but high-grade hyperglycemia was not found to be associated with severe metabolic complications. These data confirm that hyperglycemia is a common, predictable and manageable toxicity which should not impair the development of these agents.
Oxaliplatin, irinotecan, and cetuximab in advanced gastric cancer. First efficacy results of a multicenter phase II trial (AGMT Gastric-2) of the Arbeitsgemeinschaft Medikamentoese Tumortherapie (AGMT)
Authors: E. Woell, R. Greil, W. Eisterer, M. Fridrik, B. Grünberger, A. Zabernigg, B. Mayrbäurl, G. Russ, J. Thaler
Journal: Journal of Clinical Oncology (2009)

4538 Background: Patients (pts.) suffering from advanced gastric cancer have still a poor prognosis and treatment options are limited. In our previous phase II trial (AGMT-Gastric-1) we could show that the combination of oxaliplatin and irinotecan was well tolerated and showed an objective response rate of 58% (Anticancer Res 28:2901–2906, 2008). This chemotherapy regimen was tested in combination with cetuximab in a multicenter phase II trial. Methods: Oxaliplatin 85 mg/m 2 biweekly and irinotecan 125 mg/m 2 biweekly were combined with cetuximab 400 mg/m 2 loading dose and subsequently weekly 250 mg/m 2 . 51 patients with histological proven unresectable and/or metastatic gastric adenocarcinoma were treated in a first line setting. Median age: 62 years (range 19–79 years), PS 0: 25 patients, PS 1+2 26 patients, single metastatic site: 24 patients, multiple metastases: 27 patients. Results: Frequently reported adverse events (more than 20% of pts.) were predominantly grade 1 or 2 and included neutropenia (35% of pts.), thrombocytopenia (33%), anemia (73%), nausea (45%), diarrhea (57%), alopecia (22%), and fatigue (37%). Grade 3 and 4 toxicities included neutropenia in 9/1 pts., thrombocytopenia in 1/0 pts., anemia in 3/1 pts., nausea in 2/0 pts., and diarrhea in 7/2 pts. Sensory neuropathy occurred mostly as grade 1 and 2 in 37% of pts., in 7 pts. grade 3 neurotoxicity was observed. Acneiform skin rash grade 1 / 2 / 3 / 4 was reported in 31% / 20% / 6% / 2% of pts. respectively. 16 pts. went off-study due to neutropenia (n=5), nausea/vomiting (n=1), diarrhea (n=1), progressive disease (n=3), toxic colon (n=2), and allergic reaction to cetuximab at first (n=2), second (n=1) or third infusion (n=1). 35 patients are assessable for response with 1 pt. (3%) showing a CR, 21 pts. (60%) a PR, 7 pts. (20%) a SD and PD in 6 pts. (17%). A disease control rate was achieved in 83%. Median time to progression was 24.8 weeks (n=29), median overall survival 38.1 weeks (n=32). Conclusions: The combination of oxaliplatin and irinotecan with cetuximab is feasible, safe and active in advanced gastric cancer. [Table: see text]