tbuckley/cabot-search huggingface dataset:
A phase II study of capecitabine in combination with erlotinib as first-line therapy in patients with metastatic pancreatic cancer (stage IV).
Authors: S. Candamio Folgar, C. Méndez Méndez, M. Jorge Fernández, C. Romero Reinoso, G. Quintero-Aldana, M. Salgado Fernández, J. de la Cámara Gómez, M. Reboredo López, M. Ramos Vazquez, R. Lopez
Journal: Journal of Clinical Oncology (2011)

277 Background: Patients with metastatic pancreatic cancer (mPC) have poor prognosis. Given the activity of both capecitabine and erlotinib in pancreatic cancer, we hypothesized that combination use of two drugs in first-line therapy would improve clinical outcomes in these patients. Methods: A prospective, single arm, open-label, phase II study. Patients received capecitabine 1,000mg/m 2 twice daily on days 1-14 in 3-week cycles combined with erlotinib 150 mg po daily for 18 weeks, until disease progression, unacceptable toxicity or withdrawal, with a follow-up visit performed at 30-days post-treatment. The primary endpoint was objective response rate measured with RECIST criteria. Results: A total of 32 patients were evaluated. Baseline characteristics: median age was 64 years (56-70), male: 50%, Karnofsky PS ≥ 80%: 94%, tumor histology: 93.5% adenocarcinoma, 49% moderately differentiated. 11 (34%) patients had surgery, 2 (6%) had prior radiotherapy and 3 (9%) prior chemotherapy. Median treatment duration was 61 days (6-156). 3 (9%) patients required dose reduction of capecitabine and 8 (25%) of erlotinib. Of the 32 patients, 6 completed the treatment period, 22 discontinued the study prematurely due to disease progression and 4 due to AEs. Disease control rate (confirmed complete response [CR], partial response [PR] and stable disease [SD] according to RECIST criteria) was 28.2%. 2 (6.3%) patients achieved PR and 7 (21.9%) had SD. After a mean follow-up of 6.3 months, the median progression-free (PFS) and overall survival (OS) was 2.10 and 4.3 months, respectively, with a 6-months survival rate of 43.8%. Safety analysis revealed that the main grade 1/2 toxicities were rash (34%), asthenia (31%), diarrhea (31%), stomatitis (22%) and emesis (22%). Three cases of grade 3 hand-foot syndrome and 1 case of infection due to biliary stent were detected. No toxicity grade 4 occurred. Conclusions: Capecitabine administered in combination with erlotinib is an active regimen in patients with metastatic pancreatic cancer with a favourable safety profile. These results suggest that this regimen could represent a first-line treatment option for these patients. No significant financial relationships to disclose.
First-line treatment of advanced colorectal cancer with bevacizumab in France: The ThInDiT observational cohort study.
Authors: Solene Doat, Solene Samson, Philippe Ricordeau, Didier Guillemot, Emmanuel Mitry
Journal: Journal of Clinical Oncology (2012)

655 Background: ThInDiT (Therapeutic Innovations in Digestive Tumors) is an ambispective observational cohort study based on the database of the French national health insurance system. Using this database, we analysed the use of bevacizumab in the front-line treatment of metastatic colorectal cancer. Methods: Patients and treatment characteristics were collected for 4 273 incident cases of colorectal cancer with synchronous metastases diagnosed between April 1 st and September 30 th 2009. A logistic regression was used to identify factors predictive of non-prescription of bevacizumab among patients receiving chemotherapy within the first three months. Results: 2 757 (64.5%) received chemotherapy, in combination with bevacizumab in 827 patients (30% of the treated patients). Median age was 64 years in the bevacizumab group against 70 years in the no bevacizumab group (p&lt;0.0001). Major factors significantly associated with the non-prescription of bevacizumab in multivariate analysis were: age ≥ 75 years (OR= 2.47, IC95% 1.9-3.1), unresected primary tumour (OR=1.44, IC95% 1.2-1.8), rectal site (OR= 1.37, IC95% 1.1-1.8), peritoneal carcinosis (OR=1.37, IC95% 1.1-1.7), radiotherapy within the last month (OR=3.59, IC95% 2.1-6.1), arterial (OR= 1.72, IC95% 1.1-2.6) or venous (OR=2.04, IC95% 1.3-3.1) thromboembolic event within 6 months, arterial hypertension (OR=1.37, IC95% 1.1-1.7), wound (OR=3.35, IC95% 1.3-8.7), chronic bronchopneumopathy (OR=1.66, IC95%: 1.0-2.7), nephropathy (OR=2.69, IC95% 1.5-4.7). Brain metastasis and colonic endoprothesis were not associated. 1-year overall survival rate was 81% in the bevacizumab group and 76% in the no bevacizumab group. Conclusions: Based on the database of the national health insurance system, this analysis reports data on the use of chemotherapy in combination with bevacizumab in the French population, reflecting the real life practice among non-selected patients. About 2/3 of the patients with synchronous metastatic colorectal cancer are treated with chemotherapy, in combination with bevacizumab in 30% of the cases. Patients receiving bevacizumab are younger with less comorbidities.
Safer transitions of care at a major cancer center: The emergency center to hospitalist experience.
Authors: Srinivas Banala, Carmen E. Gonzalez, Norman Brito-Dellan, David Rubio, Mohamed Ait Aiss, Terry Rice, Karen Chen, Diane C. Bodurka, Carmelita P. Escalante
Journal: Journal of Clinical Oncology (2016)

247 Background: Failures in communication lead to serious medical errors particularly during transitions of care. A standardized handoff of patients requiring admission to the inpatient setting between the Emergency Center (EC) and the Hospitalist Inpatient Service (HIS) at a comprehensive cancer center was lacking during this vulnerable time. Methods: A quality pilot study using Plan, Do, Study, Act methodology was conducted. First, root cause analysis and process mapping of the current state was performed to identify pitfalls of the handoff process between the EC and the Hospitalist Service. Second, a validated standardized handoff tool, “I-PASS” (Illness severity, Patient summary, Action list, Situational awareness and contingency planning, and Synthesis by receiver) was selected and then transformed to DE-PASS, where D stands for Decisive problem requiring admission and E for Evaluation, to suit the EC workflow. The DE-PASS identified patients at higher risk for complications as urgent and emergent in the evaluation section and required a verbal communication in addition to an email using DE-PASS format. Third, we measured pre versus post intervention impact metrics. ICU transfers and Rescue Team calls within 24 hours were obtained from 822 patients. Time interval between EC admission physician order and HIS order was analyzed in a population of 174 randomly selected patients. Provider satisfaction with handoffs was surveyed. Results: The DE-PASS utilization ranged from 75% to 100% by the end of the pilot. The data analysis revealed a 60% reduction in the number of ICU transfers and a 64% reduction of Rescue Team calls post intervention. There was an 18% reduction in the interval time for an inpatient order in the medical record. EC Physicians satisfaction with DE-PASS increased by 10% and the Hospitalists increased by 40%. Conclusions: Implementation of the standardized handoff tool DE-PASS led to improved communication between two clinical services of a major cancer center. Patients’ safety improved by designation of risk stratification and reducing the time to evaluate unstable patients by the receiving HIS. Physician’s satisfaction with the handoff process increased.
Association of cross-talk between α1D-adrenergic receptor (α1D -AR) and transient receptor potential vanilloid 1 (TRPV1) with the proliferation of PC3 prostate cancer cells.
Authors: Giorgio Santoni, Valerio Farfariello, Maria Beatrice Morelli, Sonia Liberati, Massimo Nabissi, Matteo Santoni, Alessandro Piergentili, Wilma Quaglia, Consuelo Amantini
Journal: Journal of Clinical Oncology (2013)

87 Background: Growing evidence supports the role of α1-ARs in the direct mitogenic effect of catecholamines on prostate cancer (PC) cell growth. The expression of α 1D -AR on PC3 prostate cancer cells and the ability of noradrenalin (NA) to stimulate PC3 cell proliferation in a α 1D -AR-dependent manner were reported (Quaglia et al., 2005). In addition, TRPV1 expression was also found in prostate cancers (Sanchez et al., 2006). Aim of this study was to investigate the relationship between α 1D -AR and TRPV1 receptors and the involvement of TRPV1 in NA-induced proliferation in PC3 cells. Methods: By western blot analysis and confocal microscopy the expression α 1D -AR and TRPV1 and localization in PC3 cells were evaluated. PC3 cells were incubated with NA alone or in combination with WS433 and capsazepine (CPZ), α 1D -AR and TRPV1 antagonists. Proton release, calcium influx and cell proliferation were assessed in α 1D -AR-, TRPV1- or α 1D -AR/TRPV1 double-silenced PC3 cells by cytosensor and cytofluorymetric analyses. Finally, lysates from NA-treated PC3 cells alone or in combination with WS433 or CPZ were blotted with anti-phospho ERK, anti-ERK and anti-phospho-(Ser) PKC substrate Abs and Inositol-1,4,5-trisphosphate [3H] radioreceptor assay were performed. Results: α 1D -AR and TRPV1 co-localize and are co-immunoprecipitated in PC3 cells. Treatment of PC3 cells with NA strongly stimulated proton release, calcium influx and cell proliferation that were reverted by α 1D -AR WS433 and TRPV1 antagonist. NA-induced increase of survival and proliferation was totally abrogated in α 1D -AR/TRPV1 silenced cells. In addition, NA stimulates ERK and PKC substrate phosphorylation that was inhibited by WS433 and CPZ. Finally, CPZ treatment inhibited NA-dependent PLC activation, while WS433 had no effect. Conclusions: A functional and structural cross-talk between α 1D -AR and TRPV1 receptors control NA-induced proliferation of PC cells. These data strongly suggest the development of new pharmaceutical approaches based on bifunctional antibodies and molecules recognizing both α 1D -AR and TRPV1 receptors.
A randomized phase III study of elacytarabine versus limited investigator’s choice in patients with refractory acute myeloid leukemia (AML).
Authors: D. Rizzieri, N. Vey, M. Gobbi, D. L. D. Selleslag, M. W. Dennis, K. Kuliczkowski, U. Krug, F. Moscardo, D. Bron, A. D. Moicean, A. Venditti, T. F. Jacobsen, O. Foss, F. J. Giles
Journal: Journal of Clinical Oncology (2011)

TPS206 Background: Elacytarabine is a novel chemical entity developed as an antineoplastic agent. It is a fatty acid derivative (elaidic acid ester) of cytarabine (Ara-C). In contrast to cytarabine, preclinical data show that elacytarabine is independent of transporters (hENT1) to enter leukemic cells, and might therefore overcome one of the resistance mechanisms for cytarabine. Elacytarabine has in a phase II study (61 patients with 2nd salvage AML), shown a median survival of 5.3 months compared to 1.5 months in a matched historical control population The remission rate was 18% versus 4.1% and the short term mortality was 13% (O’Brien et al, EHA abstract 2010). Methods: The pivotal phase III study (CLAVELA) is an open-label, randomized controlled trial designed to compare efficacy and safety of elacytarabine single agent with a limited investigator's choice of treatment in patients with refractory AML. The primary objective is to compare overall survival and secondary objectives are to compare the response rates, duration of response, and safety profile of elacytarabine with investigator's choice treatments (HIDAC, MEC, FLAG/FLAG-IDA, Low-dose Ara-C, hypomethylating agents, hydroxyurea or palliative care). The investigator will determine the control treatment prior to randomization. In addition, blast cells will be collected for exploratory hENT analysis and the effect on possible outcome will be studied. The study is powered to detect a hazard ratio of 0.70, i.e. a 30% proportional reduction in mortality with 80% power at the p<0.05 significance level. This requires 250 deaths (events of interest). A total of up to 350 patients will be recruited at 75 sites in the USA, Canada, Australia and Europe. The DMC last reviewed the trial in November 2010 and suggested that the trial continue as planned. The key inclusion criteria: Adult patients with AML, who have received 2 or 3 previous induction regimens, and never attained a CR or failed initial induction, attained CR after salvage therapy(ies), and relapsed after < 6 months or attained CR after initial induction, relapsed after < 12 months and failed to respond to salvage therapy(ies) or relapsed within < 6 months after the latest CR.
Prospective phase II study of inoperable pancreatic adenocarcinoma with neoadjuvant gemcitabine, docetaxel, and capecitabine (GTX).
Authors: Anthony Paul Gulati, Stephen M. Schreibman, Beth Schrope, James A. Lee, John Allendorf, John A. Chabot, Dawn Tsushima, Kelley B. Mowatt, Anna Oprescu, Kyung Chu, William H. Sherman, Ronald D. Ennis, Yoomi Lee, Robert Lance Fine
Journal: Journal of Clinical Oncology (2014)

274 Background: Chemoradiation (CRT) is used in unresectable pancreatic cancer (PC) to convert patients to a resectable state. Those who go to surgery can have a similar survival as those initially deemed resectable, with a mOS of 8.2-9 mo. We recently reported a prospective phase II trial of our synergistic regimen (GTX) for patients with metastatic PC with a mOS of 14.7 mo. Methods: 35 patients with ECOG PS 0-2 and completely unresectable advanced PC (localized to the pancreas, small bowel, stomach and/or encasing at least 2 vessels such as the SMA, CA, HA, PV, or SMV) were treated with GTX: Capecitabine (Xeloda) PO 1500mg/m 2 divided into 2 doses daily on days 1-14, gemcitabine 750mg/m 2 IV given over 75 min on days 4 &amp; 11, docetaxel 30mg/m 2 IV infusion over 30 minutes preceded by dexamethasone 10mg IV/PO on days 4 &amp; 11, in a 21 day cycle. 3 cycles were given before evaluation. If eligible, a patient was allowed to proceed to surgery without radiation. Otherwise, starting on week 12, 5040 cGy of conformal radiation was given over 5-6 weeks (Mon-Fri) with weekly gemcitabine 250-300mg/m 2 IV infusion over 30 min. No adjuvant treatment was given on protocol. Primary objective was conversion rate to operable status, and secondary objectives included RR (based upon RECIST), OS, and PFS. Results: Duration of neoadjuvant chemotherapy was 9 weeks and 0% showed POD during this time. 20 of 35 patients (57%) became eligible for surgery. Of all 35 patients, there was a 49% rate of negative margins at surgery (in 85% of those patients who underwent surgery). 23 patients (66%) underwent CRT, and 11 of them (48%) ultimately went to surgery and had clean margins. Median OS from initiation of chemotherapy for all patients was 17.4 mo and &gt;22 mo if they went to surgery (20/35 pts, 1 alive). PFS of patients who underwent surgery was 13.2 mo. Grade 3/4 toxicities primarily included neutropenia (25%), leukopenia (11%), and diarrhea (6%). No deaths were attributed to GTX. Conclusions: Neoadjuvant GTX +/- radiation with gemcitabine can be used as an effective treatment for patients with truly unresectable PC. Clinical trial information: NCT00869258.
Breast cancer recurrence risk-reduction beliefs and behaviors among African American breast cancer survivors.
Authors: Selina Smith, Benjamin E. Ansa, Wonsuk Yoo, Mary S. Whitehead, Steven S. Coughlin
Journal: Journal of Clinical Oncology (2016)

180 Background: A growing body of evidence suggests that breast cancer (BC) recurrence risk is linked to lifestyle behaviors. This study examined correlations between BC recurrence, risk reduction beliefs and related behaviors among African American (AA) breast cancer survivors (BCSs). Methods: 191 AA BCSs, mean age = 56.3 years (standard deviation = 11.4 years) completed a lifestyle assessment tool. Results: Most respondents believed that being overweight (52.7%), lack of physical activity (48.7%) and a high fat diet (63.2%) are associated with BC recurrence. 66.3% considered themselves overweight; one third (33.5%) endorsed that losing weight could prevent BC recurrence; another third (33%) did not, while the remainder (33.5%) don’t know; and nearly half (47.9%) believed that BC recurrence could be prevented by increasing physical activity. 87.3% survivors with BMI &lt; 25 Kg/M 2 reported no recurrence compared to 75.7% with BMI &gt; 25 Kg/M 2 (p = 0.0580); almost all the women (99.2%) answered ‘yes’ to seeking professional help to lose weight, 79.7% of which were recurrence-free (p = 0.0508). Conclusions: These results provide information about AA BCSs’ beliefs and behaviors protective against BC recurrence. Additional research is warranted to determine the effectiveness of educational interventions for AA BCSs that promote consumption of a healthy diet and engaging in regular physical activity.
Refining the clinical trials assessment of infrastructure matrix tool.
Authors: Bryan Weiner, Randall Teal, Eileen P. Dimond, Marjorie J. Good, Angela Carrigan, Diane C. St. Germain, Andrea Denicoff, Worta J. McCaskill-Stevens, Kandie Dempsey, Robin Zon, Stephen S. Grubbs
Journal: Journal of Clinical Oncology (2014)

230 Background: Many community cancer research programs aim to exceed Good Clinical Practices. To support such efforts, the National Cancer Institute and collaborators began developing the Clinical Trials Assessment of Infrastructure Matrix (CT AIM) Tool in 2008. CT AIM’s 3 levels of exemplary performance span 11 infrastructure attributes. 2013’s revisions focused on interpretability, usability, and measurability. Methods: Tool input was obtained at national research meetings. Also, 4 Principal Investigator-Program Administrator (PI/PA) pairs from NCI-funded community cancer programs with varied demographics (eg, size, population) underwent cognitive interviews. Aggregated responses and a major-themes summary led to tool revisions. Next a web-based version was piloted with 4 more PI/PA pairs. The frequency/distribution of responses within pairs was assessed. The revised tool was then field-tested with 9 more PIs and scoring method feedback was collected; the tool was further revised. Results: Per community input and cognitive interviews: (1) “best practice” designation was replaced with “assessment of infrastructure”, (2) attributes were reordered based on perceived importance, (3) terms and cumulativeness of levels were clarified. Receiving 0 “don’t understand”s indicated improvement in clarity. 64% of “don’t know” responses were from respondents at the same program and 5 were from the biospecimen research attribute, indicating the information is difficult for programs to obtain. PI/PA responses varied 36% of the time, of which 70% involved a 1-level difference in response, indicating variation in responses by program role. 2 questions generated inconsistent responses from all 4 pairs, indicating possible further revisions. Average scoring was more accurate and sensitive to incremental program improvements. Conclusions: Broad community input, cognitive interviews, and piloting improved the tool’s clarity. Program leaders are encouraged to use CT AIM with research team members to enhance site infrastructure. CT AIM is useful for quality improvement, benchmarking research performance, progress reporting, and communicating program needs with institutional leaders. NCI Contract No. HHSN261200800001E
Trends in diagnosis and treatment for people with dementia in the UK from 2005 to 2015: a longitudinal retrospective cohort study
Authors: Katherine Donegan, Nick Fox, Nick Black, Gill Livingston, Sube Banerjee, Alistair Burns
Journal: The Lancet Public Health (2017)

The objectives of this study were to describe changes in the proportion of people diagnosed with dementia and the pharmacological treatments prescribed to them over a 10 year period from 2005 to 2015 at a time of UK policy strategies and prioritisation of dementia. We aimed to explore the potential impact of policy on dementia care.In this longitudinal retrospective cohort study, we included all patients registered at a Clinical Practice Research Datalink (CPRD) practice between July 1, 2005, and June 30, 2015, with a diagnosis of dementia defined using Read codes. The main outcomes were the number and proportion of acceptable patients, who met the CPRD threshold for data quality, in a GP practice defined by the CPRD as contributing up-to-standard data with a diagnosis of dementia and the number and proportion of these with a prescription for an antidementia or antipsychotic medication. We examined the prevalence of dementia diagnosis and prescribing by calendar quarter, and stratified by age, sex, and UK country (England, Scotland, Wales, or Northern Ireland). We investigated the use of antidementia drugs, alone and in combination, antipsychotics, antidepressants, anxiolytics, and hypnotics. The trend in the proportion of patients with a diagnosis of dementia, before and after the introduction of the UK National Dementia Strategy, was estimated using an interrupted time-series analysis.8 966 224 patients were identified in the CPRD whose most recent registration period overlapped the study period. Of these, 128 249 (1·4%) had a diagnosis of dementia before the end of the study period. The proportion of people diagnosed with dementia in the UK doubled from 0·42% (19 635 of 4 640 290 participants) in 2005 to 0·82% (25 925 of 3 159 754 participants) in 2015 (χ2 test for trend, p<0·0001), and the proportion of those who received antidementia medication increased from 15·0% (2942 of 19 635) to 36·3% (9406 of 25 925). The interrupted time-series analysis showed a significant acceleration in the rate of diagnosis of dementia after the introduction of the UK National Dementia Strategy (p<0·0001). There was a large reduction in antipsychotic drug prescription in dementia from 22·1% (4347 of 19 635) in 2005 to 11·4% (2943 of 25 925) by 2015.Over the 10 years studied, there is evidence of a sustained positive change in diagnosis rates of dementia and in the quality of drug treatment provided to those diagnosed. The prescription of antidementia drugs more than doubled and the prescription of potentially hazardous antipsychotics halved after the introduction of national dementia strategies. These data support the formulation and delivery of national policy to improve the quality of care for people with dementia.None.