tbuckley/cabot-search huggingface dataset:
A phase I/II trial of continuous hepatic intra-arterial infusion of 5-fluorouracil, mitoxantrone, and cisplatin (FMP therapy) for advanced hepatocellular carcinoma.
Authors: M. Ikeda, T. Okusaka, H. Ueno, C. Morizane, K. Nakachi, S. Mitsunaga, Y. Sato, Y. Inaba, M. Satake, Y. Arai
Journal: Journal of Clinical Oncology (2010)

e14556 Background: The aim of this study was to investigate the maximum-tolerated dose and determine the recommended dose, based on the frequency of dose-limiting toxicities, of continuous hepatic intra-arterial infusion of 5-fluorouracil, mitoxantrone and cisplatin (FMP therapy) in a phase I study protocol, and to evaluate the efficacy and toxicity of FMP therapy at the recommended dose for advanced hepatocellular carcinoma (HCC) in a phase II study protocol. Methods: Forty-five patients with advanced HCC who were not candidates for surgical resection, local ablation or transcatheter arterial embolization, had no history of prior chemotherapy, were enrolled. The therapy consisted of intra-arterial administration of cisplatin (P) and mitoxantrone (M) on day 1, and continuous intra-arterial infusion of 5-fluorouracil (F) from day 1 through day 5 (F/M/P[mg/m2]: Level1; 400/4/60, Level 2; 400/6/60, Level 3; 500/6/60). The treatment was repeated every four weeks for a maximum of six courses, until the appearance of evidence of tumor progression or of unacceptable toxicity. Results: In the phase I part of the study, one of six patients at level 1 developed DLT, including grade 3 pulmonary embolism, while none of the patients at either level 2 or 3 exhibited any signs of dose-limiting toxicity. Therefore, the recommended dose of FMP therapy was determined to be the level 3 dose. In the phase II part, 36 patients were enrolled. Nine patients (25%) achieved a partial response, and the response rate was 25% (95% confidence interval: 12- 42%). The overall median survival time, 1-year survival rate and median progression-free survival were 11.3 months, 46.9% and 7.0 months, respectively. The main grade 3 and 4 hematological and non-hematological toxicities were leukopenia (36%), neutropenia (39%) and thrombocytopenia (19%), and elevation of the serum levels of aspartate aminotransferase (22%) and alanine aminotransferase (14%). These toxicities were generally transient and well tolerated. Conclusions: In patients with advanced HCC, hepatic arterial infusion of FMP was feasible, however, no favorable tumor response or survival benefit could be demonstrated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly, Taiho Pharmaceutical
A phase I study of S-1 GI toxicity with and without oxonic acid (Oxo)
Authors: L. I. Chap, I. Laux, A. Van Vugt, A. M. Silva, A. Khashi, J. Zhang, C. Zergebel, P. D. Urrea, L. S. Rosen
Journal: Journal of Clinical Oncology (2008)

13539 Background: S-1 is a fixed combination drug composed of a prodrug of 5-FU (FT), a dihydropyrimidine dehydrogenase (DPD) inhibitor (CDHP), and an inhibitor of 5-FU phosphorylation (Oxo). Due to its GI distribution, the Oxo component of S-1 is expected to protect against 5-FU-evoked GI toxicity without affecting systemic 5-FU exposure. The purpose of this study is to investigate the GI toxicity and dose- limiting toxicities (DLTs) of S-1 (FT+CDHP+Oxo) compared with CFT (FT+CDHP; no Oxo) in a dose escalation design. Methods: Patients with advanced refractory/relapsed solid tumors were randomized to receive either S-1 or CFT administered at 25 mg/m2 bid for 21 days followed by 7 days rest. Dose escalation was planned by 5 mg/m2 increments, with 6 patients maximum per dose level, until 2 DLTs were observed. DLT was defined as G4 hematologic/ ≥G3 non-hematologic treatment-related toxicity in cycle 1. Plasma samples were collected for determination of concentrations of FT, 5-FU, CDHP, Oxo and metabolites. After cycle 1, patients could enroll in an extension phase where all patients received S-1 on the same schedule. Results: A total of 12 patients were enrolled (S- 1=7, CFT=5); 11 (S-1=6, CFT=5) patients were evaluable for DLT. At the 25 mg/m2 dose level, 2 events of G3 diarrhea and 1 sudden death occurred on the CFT arm during cycle 1, while no DLT or drug-related G3/4 events were reported on the S-1 arm. In accordance with the protocol rules, the study was stopped without further dose escalation. S-1 was generally well tolerated in the subsequent extension phase (cycles >1); the most common S-1 related events were fatigue, nausea, and diarrhea. No drug-related G3/4 events were reported for patients in the S-1 arm at any time during study. Single dose PK parameters for FT, 5-FU, CDHP were similar for both S-1 and CFT arms. Conclusions: The Oxo component of S-1 contributes a GI protective effect and a favorable GI safety profile. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Taiho Taiho
Chemoradiation for locally advanced penile squamous cell carcinoma (PSCC): A multi-institution retrospective study.
Authors: Bernhard J. Eigl, Gregory Russell Pond, Matthew I. Milowsky, Michael Paul Kolinsky, Andrea Necchi, Lauren Christine Harshman, Giuseppe di Lorenzo, Tanya B. Dorff, Richard J. Lee, Guru Sonpavde
Journal: Journal of Clinical Oncology (2014)

e15616 Background: Outcomes with concurrent chemoradiation for penile squamous cell carcinoma (PSCC) are unclear and only anecdotal reports have been published. We performed a retrospective analysis of patients who received concurrent chemotherapy and radiotherapy for PSCC. Methods: Individual patient level data were obtained from 5 institutions treated between 2000 and 2012. Eligibility required patients who had received concurrent systemic therapy with external beam radiotherapy without subsequent surgery for localized, locoregionally advanced or metastatic PSCC. Descriptive statistics were calculated and univariable Cox proportional hazards regression analysis was conducted to examine the prognostic impact of candidate factors on progression-free survival (PFS) and overall survival (OS). Results: A total of 26 men were evaluable. The mean age was 60.3 years (SD 12.4 years). The clinical stage was ≤3 in 9 patients (36%) and stage 4 in the rest. Soft tissue and visceral metastasis were present in 35% and 20% of patients, respectively. The chemotherapy was cisplatin-based in 92.3% of patients and the median (range) of external beam radiotherapy administered was 4900 cGy (1800-7000). The median OS was 6.9 months (95% CI: 5, 14) and the median PFS was 5.1 months (95% CI: 2.5, 7.0). When excluding patients with M1 disease, the remaining patients (N=21) had a median OS and PFS of 10.0 months (95% CI: 5, 14) and 6.0 months (95% CI: 2.0, 7.0), respectively. Only 2 patients attained durable PFS and OS >2 years. Baseline neutrophil by lymphocyte ratio (NLR) was significantly associated with OS and visceral metastasis showed a trend for association with OS. The dose of radiation was associated with a 20-30% decreased hazard of both OS and PFS for every 10 Gy increase in dose. Conclusions: Concurrent chemoradiation demonstrated poor outcomes for locally advanced PSCC. Better understanding of tumor biology and study of novel combinations of biologic agents with radiation are warranted.
TCT-620 Shift Of Patient Selection For Balloon Aortic Valvuloplasty After Introduction Of Transcatheter Aortic Valve Replacement: Insights From A Single-center Registry
Authors: Omar A. Meelu, Marco G. Mennuni, Usman Baber, Samantha Sartori, Melissa Aquino, Joe Sweeny, Pedro R. Moreno, Prakash Krishnan, Roxana Mehran, Annapoorna Kini, Samin K. Sharma, George Dangas
Journal: Journal of the American College of Cardiology (2015)
Abstract 17295: Effect of Atrial Rate-responsive Pacing in the Incidence of Sustained Atrial Arrhythmias in Patients With Implantable Cardioverter-defibrillators
Authors: Adolfo Fontenla, Maria Lopez-Gil, Jose B Martinez-Ferrer, Anibal Rodriguez, Javier Alzueta, Enrique Garcia, Nuria Basterra, Rafael Romero, Joaquin Fernandez de la Concha, Xavier Viñolas, Julian Villacastin, Rafael Salguero, Fernando Arribas
Journal: Circulation (2015)

Introduction: Atrial rate-responsive pacing (RRP) has proved to be safe in pacemaker recipients with chronotropic incompetence, but there is little data regarding its use in implantable cardioverter-defibrillator (ICD) patients. Hypothesis: Atrial RRP may increase the occurrence of sustained atrial arrhythmias when programmed in ICD recipients. Methods: Dual-chamber and triple-chamber ICD patients were included in this multicenter cohort study. Patients with permanent atrial fibrillation (AF) or VVI pacing mode were excluded. The number and duration of atrial tachycardia (AT)/AF episodes were assessed by remote monitoring. Results: Data from 415 patients was collected after a 21.3±14.1 months follow-up. Atrial RRP was programmed in 90 (21.7%) patients and was associated to a higher atrial pacing percentage in the overall study population (51.2±33.8% versus 18.4±25.7%, P&lt;0.001) and to a higher ventricular pacing percentage among dual-chamber devices (22.3±37.6% versus 9.3±25%, P 23 hours) were history of AF (odds ratio: 7.98; 95% confidence interval: 4.11-15.47; p&lt;0,001) and atrial RRP (odds ratio: 3,58; 95% confidence interval: 1.82-7.03; p&lt;0,001). RRP was related to a lower sustained AT/AF episodes-free survival both in patients with and without a history of AF (Figure). Within patients with a history of AF, atrial RRP was also associated with a higher median of AT/AF episodes/patient (18.5 [interquartile range: 339] versus 8 [69], P=0.016) and a higher percentage of time recording AT/AF (9.21% [36.32] versus 1.18% [16.31], P=0.024). Cumulative incidence of sustained AT/AF episodes &gt; 23 hours was proportional to the atrial pacing percentages. Conclusions: Atrial RRP in ICD patients was related to a higher cumulative incidence of sustained atrial arrhythmias &gt;23 hours. This pacing mode seems to have an atrial proarrhythmic effect not described up to now in ICD patients, especially among those with a history of AF.
Immunoglobulin Free Light Chain (FLC) and Heavy Chain/Light Chain (HLC) Assays – Comparison with Electrophoretic Responses in Multiple Myeloma (MM)
Authors: Parameswaran Hari, Marcelo C Pasquini, Brent R. Logan, Edward A. Stadtmauer, Amrita Krishnan, Alan Howard, Sairah Alvi, Stephen Harding, Shelly L Carter, Vincent Rajkumar, Edwin P Alyea, Muzaffar Qazilbash, Ginna G. Laport, David G. Maloney, Sergio Giralt, David H. Vesole
Journal: Blood (2011)
TCT-761 Effectiveness of Endovascular therapy for Acute Ischemic Stroke-Evidence from a Meta-analysis of Randomized Trials
Authors: Partha Sardar, Saurav Chatterjee, Anwar Tandar, Amartya Kundu, Ramez Nairooz, Jay Giri, Debabrata Mukherjee, William A. Gray, Philip Meyers
Journal: Journal of the American College of Cardiology (2015)
Chromoplectic TPM3–ALK rearrangement in a patient with inflammatory myofibroblastic tumor who responded to ceritinib after progression on crizotinib
Authors: A.S. Mansfield, S.J. Murphy, F.R. Harris, S.I. Robinson, R.S. Marks, S.H. Johnson, J.B. Smadbeck, G.C. Halling, E.S. Yi, D. Wigle, G. Vasmatzis, J. Jen
Journal: Annals of Oncology (2016)

BackgroundInflammatory myofibroblastic tumors (IMTs) are rare sarcomas that can occur at any age. Surgical resection is the primary treatment for patients with localized disease; however, these tumors frequently recur. Less commonly, patients with IMTs develop or present with metastatic disease. There is no standard of care for these patients and traditional cytotoxic therapy is largely ineffective. Most IMTs are associated with oncogenic ALK, ROS1 or PDGFRβ fusions and may benefit from targeted therapy.Patient and methodsWe sought to understand the genomic abnormalities of a patient who presented for management of metastatic IMT after progression of disease on crizotinib and a significant and durable partial response to the more potent ALK inhibitor ceritinib.ResultsThe residual IMT was resected based on the recommendations of a multidisciplinary tumor sarcoma tumor board and analyzed by whole-genome mate pair sequencing. Analysis of the residual, resected tumor identified a chromoplectic TPM3–ALK rearrangement that involved many other known oncogenes and was confirmed by rtPCR.ConclusionsIn our analysis of the treatment-resistant, residual IMT, we identified a complex pattern of genetic rearrangements consistent with chromoplexy. Although it is difficult to know for certain if these chromoplectic rearrangements preceded treatment, their presence suggests that chromoplexy has a role in the oncogenesis of IMTs. Furthermore, this patient's remarkable response suggests that ceritinib should be considered as an option after progression on crizotinib for patients with metastatic or unresectable IMT and ALK mutations.
GW27-e0251 Effect of Shenfuyixin formula on the content of ATP and expression of uncoupling protein-2 in rats with heart failure following myocardial infarction
Authors: Xie Shiyang, Youping Wang, Xiaoxiao Wang, Bin Li, Peng Chen, Cuiling Zhu, Mingjun Zhu
Journal: Journal of the American College of Cardiology (2016)
Capecitabine in combination with bendamustine in pretreated women with HER2-negative metastatic breast cancer: Efficacy results of a phase II trial (AGMT MBC-6).
Authors: Gabriel Rinnerthaler, Simon Peter Gampenrieder, Daniela Voskova, Andreas L. Petzer, Michael Hubalek, Edgar Petru, Bernd Hartmann, Johannes Andel, Marija Balic, Hanno Ulmer, Thomas Melchardt, Brigitte Mlineritsch, Richard Greil
Journal: Journal of Clinical Oncology (2016)

1032 Background: Capecitabine is a well-established treatment option in HER2-negative advanced breast cancer (ABC) patients. Bendamustine is a generally well tolerated cytotoxic drug. Since bendamustine has already shown anticancer activity in ABC we evaluated the efficacy and tolerability of bendamustine in combination with capecitabine in pretreated patients with ABC. Methods: MBC-6 is a non-randomized, multicenter, open-label, single-arm phase II study in patients with HER2-negative ABC (ClinicalTrials.gov: NCT01891227). All patients were pretreated with anthracyclines and/or taxans and had measurable disease according to RECIST 1.1. Patients received 1000 mg/m2 capecitabine twice daily on days 1 to 14 in combination with 80 mg/m2 bendamustine on day 1 and 8 of a 3-week cycle. The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), clinical benefit rate (CBR), safety and quality of life. Results: From September 2013 to May 2015, 40 patients were recruited in eight Austrian centers. Median age was 60 years (range 29-77). Twenty-five percent of patients had triple-negative disease (TNBC) and 93% showed visceral involvement. Sixty-five percent had received prior chemotherapy in the (neo)adjuvant setting and 63% for ABC (43% one line, 15% two lines, 5% three lines). All patients with ER-positive disease had received prior endocrine therapy. With 20 confirmed PR and 1 confirmed CR, ORR was 53%, 57% in ER-positive and 40% in TNBC. CBR was 60%. At data cut-off on 01/13/16 overall 32 of 40 patients had discontinued treatment with a preliminary median PFS of 8.9 months (95% CI 6.5-12.6). Fourteen patients (35%) experienced at least one drug related non-hematological AE ≥ grade 3 (all grade 3). Three grade 4 neutropenia were observed, but no case of neutropenic fever. One patient died as a result of restrictive cardiomyopathy, where a relationship to capecitabine cannot be excluded, but seems unlikely. Conclusions: The combination of capecitabine and bendamustine shows promising efficacy and a moderate toxicity profile. Further evaluation of this drug combination is warranted. Clinical trial information: NCT01891227.
Allogeneic Hematopoietic Stem Cell Transplantation from Unrelated Peripheral Blood or Bone Marrow Donors: The Impact of HLA Matching Including HLA-DPB1 Allele in a Multivariable Risk Model
Authors: Mauricette Michallet, Mohamad Sobh, Hélène Labussière-wallet, Marie Balsat, Caroline Lejeune, Sophie Ducastelle-Leprêtre, Xavier Thomas, Catherine Giannoli, Philippe Moskovtchenko, Fiorenza Barraco, Franck E. Nicolini, Valérie Dubois
Journal: Blood (2015)
TCT-636 Self-Expanding TAVR in Patients with Low-Gradient, Low Output Aortic Stenosis: 12 Month Results from the CoreValve US Expanded Use Study
Authors: Stanley J. Chetcuti, G. Michael Deeb, Kimberly A. Skelding, Alfred Casale, Ron Waksman, Ammar Bafi, Jae K. Oh, Steven Yakubov, Michael J. Reardon, David Adams, Jeffrey Popma
Journal: Journal of the American College of Cardiology (2015)
A preoperative clinical staging and metabolic imaging model to predict prognosis in early-stage esophageal adenocarcinoma.
Authors: Richard Calvin Turkington, Jaine K. Blayney, Awais Jalil, Rebecca Barbara Goody, Anastasia Papafili, Chloe Henderson, Damian McManus, Patrick Johnston, Richard D. Kennedy, Martin McKinlay Eatock
Journal: Journal of Clinical Oncology (2014)

63 Background: Accurate prediction of outcome for neo-adjuvant therapy in early stage esophageal adenocarcinoma (EAC) is essential for clinical trial design, patient counseling and treatment decisions. The use of 18F-fluorodeoxyglucose positron emission tomography (PET) has improved the staging of EAC and can predict pathological response and survival. Our aim was to develop a pre-operative prognostic model based on metabolic imaging and clinical parameters. Methods: Between April 2004 and December 2010, 118 patients with early stage adenocarcinoma of the distal esophagus or gastro-esophageal junction were treated with platinum and fluorouracil-based combination chemotherapy prior to surgical resection. Patients were staged by endoscopic ultrasound and PET/CT was performed prior to, and upon completion of, chemotherapy. A metabolic response was defined as a &gt;35% reduction in the maximum standard uptake variable (SUV max ). The final prognostic model was selected by multivariate Cox regression analyses and the concordance-index (c-index) was used to assess the fit of the final multivariate model. Results: In both the univariate and multivariate analysis of patient prognosis post-surgery, five pre-surgery factors were included: clinical T and N staging, PET response, neutrophil-lymphocyte ratio and albumin levels. The majority of the patients were T3 (82.1%) and N1 (73.7%) and 69.8% of patients demonstrated a PET response. In the univariate analysis PET response was the only significant prognostic factor with a median overall survival (OS) of 60.4 months for responders compared to 23.3 months for non-responders (p=0.0241). The final multivariate model of T staging and PET response had a c-index of 0.624 with T3/PET non-response resulting in a poorer prognosis compared to T3/PET response and T2/PET responder or non-responder (median OS 11.5 vs 44.5 vs undefined months; p=0.0284). We seek to validate our model in an independent patient dataset to assess its predictive capability. Conclusions: Metabolic imaging and clinical staging can be combined in a prognostic model in early stage EAC. Our model can inform patient counseling and the development of clinical trial strategies.
Efficacy and Safety of Bosutinib (SKI-606) in Patients with Chronic Phase (CP) Ph+ Chronic Myelogenous Leukemia (CML) with Resistance or Intolerance to Imatinib.
Authors: Jorge Cortes, Hagop M Kantarjian, Dong- Wook Kim, H. Jean Khoury, Anna G. Turkina, Zhi-Xiang Shen, Tim H Brummendorf, Mammen Chandy, Steven Arkin, Carlo Gambacorti-Passerini
Journal: Blood (2008)
Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers
Authors: Andreas Ø Bielefeldt, Pia B Danborg, Peter C Gøtzsche
Journal: Journal of the Royal Society of Medicine (2016)

Objective To quantify the risk of suicidality and violence when selective serotonin and serotonin-norepinephrine reuptake inhibitors are given to adult healthy volunteers with no signs of a mental disorder. Design Systematic review and meta-analysis. Main outcome measure Harms related to suicidality, hostility, activation events, psychotic events and mood disturbances. Setting Published trials identified by searching PubMed and Embase and clinical study reports obtained from the European and UK drug regulators. Participants Double-blind, placebo-controlled trials in adult healthy volunteers that reported on suicidality or violence or precursor events to suicidality or violence. Results A total of 5787 publications were screened and 130 trials fulfilled our inclusion criteria. The trials were generally uninformative; 97 trials did not report the randomisation method, 75 trials did not report any discontinuations and 63 trials did not report any adverse events or lack thereof. Eleven of the 130 published trials and two of 29 clinical study reports we received from the regulatory agencies presented data for our meta-analysis. Treatment of adult healthy volunteers with antidepressants doubled their risk of harms related to suicidality and violence, odds ratio 1.85 (95% confidence interval 1.11 to 3.08, p = 0.02, I 2 = 18%). The number needed to treat to harm one healthy person was 16 (95% confidence interval 8 to 100; Mantel-Haenszel risk difference 0.06). There can be little doubt that we underestimated the harms of antidepressants, as we only had access to the published articles for 11 of our 13 trials. Conclusions Antidepressants double the occurrence of events in adult healthy volunteers that can lead to suicide and violence.
BMI1 Collaborates with RUNX1/AML1 Mutants in the Development of Human Myelodysplastic Syndrome (MDS) / Acute Myeloid Leukemia (AML)
Authors: Hironori Harada, Ye Ding, Jun Imagawa, Takahiko Miyama, Akiro Kimura, Yuka Harada
Journal: Blood (2011)
Prognostication of survival from nasopharyngeal carcinoma by reduction of plasma Epstein-Barr viral DNA load at midpoint of radiotherapy course: A new paradigm of prognostication.
Authors: Anthony T. C. Chan, Allen K.C. Chan, Brigette Ma, Edwin Pun Hui, Frankie Mo, Katherine Chow, Linda Leung, Ka Wah Chu, Benny C.Y. Zee, Dennis YM Lo, Sing Fai Leung
Journal: Journal of Clinical Oncology (2013)

6015 Background: To test the hypothesis that prognostication of treatment outcome is feasible by biomarker response at mid-course of chemoradiotherapy (CRT)/ radiotherapy (RT), with respect to the plasma load of Epstein-Barr viral (EBV) DNA in nasopharyngeal carcinoma (NPC). Methods: 107 patients with stage IIB-IV NPC were prospectively studied. Plasma EBV DNA load was measured by quantitative PCR before therapy (pre-DNA), at completion of 4 weeks of CRT/RT (mid-DNA), and within 3 months of completion of therapy (post-DNA). The endpoints are post-DNA load, a recognized surrogate of survival, and clinical outcome. Results: 93% of patients had detectable EBV DNA before therapy (median load = 972 copies/ml). EBV DNA became undetectable in 55 (51%) patients at the end of week 4 of therapy. Detectable mid-DNA was associated with worse clinical outcome (median follow-up time, 6.2 years), for distant failure (HR 12.02, 95% CI 2.78-51.93; P&lt;0.0001), progression-free survival (HR 4.05, 95% CI 1.89-8.67, P&lt;0.0001), and overall survival (HR 3.29, 95% CI 1.37-7.90, P=0.0077). About three-quarters of all failures were associated with detectable mid-DNA, whereas about one-third of all failures were associated with detectable post-DNA. Patients with detectable mid-DNA which disappeared after RT continued to sustain a less favourable prognosis than those with undetectable mid-DNA. Stratification by tumor stage (II, III, IV) has no significant prognostic effect. Conclusions: Unfavorable EBV DNA response at mid-course of radiotherapy/chemoradiotherapy is an adverse prognosticator for treatment outcome, is linked to majority of all failures, and discriminates outcome better than tumor stage. The data could provide a basis for trial design that addresses alteration of therapy intensity during the latter phase of chemoradiotherapy, and adjuvant therapy.