tbuckley/cabot-search huggingface dataset:
High complete response (CR) rate in patients (pts) with esophageal carcinoma (EC) undergoing neoadjuvant combination of docetaxel and cisplatin (DC) ± cetuximab(DCE) chemoradiation therapy—a retrospective analysis
Authors: T. J. Fillos, P. Hentschel, K. Watkins, M. S. Karpeh, A. Meek, B. Kim, D. Franceschi, S. Zee, S. Madajewicz
Journal: Journal of Clinical Oncology (2007)

15093 Background: EC is a highly lethal disease with 5 year survival less than 15%. Surgery offers a chance for cure in early disease. Still, fewer than 20% of pts treated with surgery alone are alive at 5 years. Neoadjuvant chemoradiation offers the theoretical advantage of increasing R0 resections and reducing early local and distal metastases which may translate into improved survival. Several clinical trials have resulted in pathologic complete response (pCR) rates of 20–30%. Methods: Newly diagnosed pts with EC Stage 2A (T3) to 4 received weekly Docetaxel (D)25–30mg/m2 and Cisplatin (C)25–30mg/m2.for 6–8 weeks concurrently with radiation, 5040 cGy in 28 fractions. Cetuximab (E) 200mg/m2 was added after it became accepted treatment in head and neck cancers. Pts were scheduled 4 - 6 weeks later for surgery followed by the same chemotherapy for total of 16 weeks of treatment. Pts were assessed for time to progression, overall survival and toxicities. Results: Fifteen pts treated in 2005–6 underwent IRB approved evaluation; 11 male and 4 female, median age of 62(range 44–78) . Four had squamous cell (SCC) and 11 adenocarcinomas. Nine pts had Stage II, 4 pts stage III and 2 pts stage IV disease. Seven pts underwent surgery, all R0 resections. Four of them had pCR, one pPR (downstaged from T3 to T1) and two pts had stable disease. An additional 3 pts had radiological and endoscopic proven CR (medically not surgical candidates) for an objective response (CR+PR) in 8 out of 15 pts (3 SCC and 5 adenoca). Five out of 9 receiving DC had an objective response while 3 of 6 receiving DCE responded. Five pts progressed prior to surgery. Grade 3/4 neutropenia occurred in 2, nausea in 3, and 1 pt experienced Grade 3 dehydration. Four patients required dose reductions by 20%. Six patients had one cycle and 2 had 3 cycles delayed by one week each. Conclusions: Neoadjuvant chemoradiation treatment with weekly Docetaxel and Cisplatin ± Cetuximab is tolerable with high rate of CRs. There was no observed difference in response with the addition of cetuximab. A Phase III study is suggested. No significant financial relationships to disclose.
Abstract 13223: Evaluation of a New Strain Analysis Program Developed for Small Animal Imaging: Validation Against Sonomicrometry
Authors: Muhammad Ashraf, William H Packwood, Meihua Zhu, Andrew Nickerson, Cole Streiff, Xubo Song, David J Sahn
Journal: Circulation (2012)

Background: Small animal imaging is an integral part of imaging research. The aim of this study was to test a new motion analysis program developed for very high frame rate 2D images from small animals. Methods: Ten C57BL/6 mice were subjected to left lateral sternotomies under inhalation anesthesia and continuous monitoring. Two 0.7 mm sonomicrometry crystals were attached along the circumference of the mouse heart. Each mouse was subjected to pharmacological intervention using intravenous infusion of dobutamine (30 ng/gm BW/min) and esmolol (10 mcg/gm BW/min) to change the heart rate no more than 10-15% from the baseline, allowing complete recovery to basal heart rate between and after interventions. Myocardial ischemia was produced by ligating the left anterior descending aorta (LAD) at the end of study. At each steady state, short axis views were acquired using an MS-550S probe on a Vevo 2100 ultrasound system at frame rates >300fps directly from the surface of the heart. Image data was analyzed for c...
Warfarin and small-cell lung cancer.
Authors: M H Huber, W K Hong
Journal: Journal of Clinical Oncology (1993)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1993.11.2.383 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8381165 Warfarin and small-cell lung cancer. M H HuberxM H HuberSearch for articles by this author , W K HongxW K HongSearch for articles by this author https://doi.org/10.1200/JCO.1993.11.2.383 PDF "Warfarin and small-cell lung cancer.." Journal of Clinical Oncology, 11(2), p. 383© 1993 by American Society of Clinical Oncology
Neurophenotypes in Airway Diseases. Insights from Translational Cough Studies
Authors: Maria G. Belvisi, Mark A. Birrell, Saifudin Khalid, Michael A. Wortley, Rachel Dockry, Julie Coote, Kimberley Holt, Eric Dubuis, Angela Kelsall, Sarah A. Maher, Sara Bonvini, Ashley Woodcock, Jaclyn A. Smith
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Most airway diseases, including chronic obstructive pulmonary disease (COPD), are associated with excessive coughing. The extent to which this may be a consequence of increased activation of vagal afferents by pathology in the airways (e.g., inflammatory mediators, excessive mucus) or an altered neuronal phenotype is unknown. Understanding whether respiratory diseases are associated with dysfunction of airway sensory nerves has the potential to identify novel therapeutic targets.To assess the changes in cough responses to a range of inhaled irritants in COPD and model these in animals to investigate the underlying mechanisms.Cough responses to inhaled stimuli in patients with COPD, healthy smokers, refractory chronic cough, asthma, and healthy volunteers were assessed and compared with vagus/airway nerve and cough responses in a cigarette smoke (CS) exposure guinea pig model.Patients with COPD had heightened cough responses to capsaicin but reduced responses to prostaglandin E2 compared with healthy volunteers. Furthermore, the different patient groups all exhibited different patterns of modulation of cough responses. Consistent with these findings, capsaicin caused a greater number of coughs in CS-exposed guinea pigs than in control animals; similar increased responses were observed in ex vivo vagus nerve and neuron cell bodies in the vagal ganglia. However, responses to prostaglandin E2 were decreased by CS exposure.CS exposure is capable of inducing responses consistent with phenotypic switching in airway sensory nerves comparable with the cough responses observed in patients with COPD. Moreover, the differing profiles of cough responses support the concept of disease-specific neurophenotypes in airway disease. Clinical trial registered with www.clinicaltrials.gov (NCT 01297790).
Phase I clinical trial of taxotere administered as either a 2-hour or 6-hour intravenous infusion.
Authors: H Burris, R Irvin, J Kuhn, S Kalter, L Smith, D Shaffer, S Fields, G Weiss, J Eckardt, G Rodriguez
Journal: Journal of Clinical Oncology (1993)

PURPOSE To determine the potential efficacy and dose-limiting toxicity of taxotere, a hemisynthetic inhibitor of tubulin depolymerization. PATIENTS AND METHODS Fifty-eight patients were administered taxotere in this phase I clinical trial as a 6-hour or a 2-hour infusion repeated every 21 days. Forty patients received 181 courses on the 6-hour infusion schedule, and 18 patients received 105 courses on the 2-hour infusion schedule. RESULTS Neutropenia was the dose-limiting toxicity on both schedules. The maximally tolerated dose was 100 mg/m2 on the 6-hour infusion schedule and 115 mg/m2 on the 2-hour infusion schedule. The most prominent nonhematologic toxicities included mucositis (more prominent on the 6-hour infusion schedule), transient rash (more common on the 2-hour infusion schedule), and alopecia. Hypersensitivity reactions were seen in five patients. There was no evidence of neurotoxicity or cardiotoxicity. One partial response was noted on the 6-hour infusion schedule (one in refractory breast cancer) and four additional partial responses were noted on the 2-hour infusion schedule (two in adenocarcinoma of the lung, one in refractory breast cancer, one in cholangio-carcinoma). In addition, 10 patients had minor responses. Pharmacokinetic studies showed plasma concentrations of taxotere declined in a triexponential manner, with a terminal half-life of 11.8 hours. CONCLUSION The recommended starting dose for phase II taxotere trials is 100 mg/m2 administered as a 2-hour infusion, repeated every 21 days. Taxotere is a promising antineoplastic agent worthy of extensive phase II testing in patients with a variety of malignancies.
ABX-EGF monotherapy in patients (pts) with metastatic colorectal cancer (mCRC): An updated analysis
Authors: J. R. Hecht, A. Patnaik, I. Malik, A. Venook, J. Berlin, G. Croghan, B. L. Wiens, S. Visonneau, S. Jerian, N. J. Meropol
Journal: Journal of Clinical Oncology (2004)

3511
Synthesis and dephosphorylation of MARCKS in the late stages of megakaryocyte maturation drive proplatelet formation
Authors: Kellie R. Machlus, Stephen K. Wu, Deborah J. Stumpo, Thomas S. Soussou, David S. Paul, Robert A. Campbell, Hermann Kalwa, Thomas Michel, Wolfgang Bergmeier, Andrew S. Weyrich, Perry J. Blackshear, John H. Hartwig, Joseph E. Italiano
Journal: Blood (2016)
Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation
Authors: Christoph Schmid, Myriam Labopin, Gerard Socié, Etienne Daguindau, Liisa Volin, Anne Huynh, Jean Henri Bourhis, Noel Milpied, Jan Cornelissen, Patrice Chevallier, Johan Maertens, Pavel Jindra, Didier Blaise, Stig Lenhoff, Norbert Ifrah, Frédéric Baron, Fabio Ciceri, Claude Gorin, Bipin Savani, Sebastian Giebel, Emmanuelle Polge, Jordi Esteve, Arnon Nagler, Mohamad Mohty
Journal: Blood (2015)
Abstract 19081: 5-lipoxygenase Inhibitor Via-2291 (atreleuton) Reduces Inflammation and Coronary Necrotic Core Plaque and Improves Left Ventricular Function in Patients After an Acute Coronary Syndrome
Authors: Naser Ahmadi, Vahid Nabavi, Reuben J Ram, Ferdinand Flores, Michael Baskett, Philippe L L'Allier, Josephine Pressacco, Jean-Claude Tardif, Matthew Budoff
Journal: Circulation (2012)

Background: The 5-lipoxygenase inhibitor VIA-2291 effectively lowers production of leukotriene metabolites. This study investigates the relations between inflammation, coronary plaque characteristics and left ventricular function in response to treatment with VIA-2291 (Atreleuton) in patients after an acute coronary syndrome (ACS). Methods: Fifty six post-ACS patients who participated in a randomized trial evaluating the effects of VIA-2291 vs. placebo and underwent cardiac computed tomography angiography were studied. Leukotriene E4 (LTE4), high-sensitivity C-reactive protein (hs-CRP), coronary plaque volume (PV) with vulnerable characteristics (Necrotic Core) and left ventricular ejection fraction (LVEF) were measured at baseline and at 6-month follow-up. The relation of changes in LTE4, hs-CRP, PV and LVEF in response to VIA-2291 was analyzed using conditional logistic regression analyses. Results: From baseline to 6 months, after adjustment for risk factors, significant reductions in LTE4, hs-CRP and VP, and an increase in LVEF with VIA-2991 as compared to placebo were noted (p&lt;0.05, Table).After adjustment for risk factors, there were strong associations between the decrease in LTE4, the decrease in necrotic core PV and the increase in LVEF (Table); 71% and 79% of the variance in PV and LVEF was explained by the decrease in LTE4 in response to VIA-2991 (p&lt;0.05). The maximum improvement in LVEF was noted with maximum decrease in LTE4 and PV. Conclusion: This study documented a strong relation between decreases in LTE4, decreases in necrotic core coronary plaque volume and improved LV function in response to VIA-2291.
An observational prospective study on central venous devices (CVD) use in oncologic patients: Registro CVD - PoloNord
Authors: G. Aondio, D. Fagnani, C. Porta, R. Franchi, M. Fiumanò, M. Giordano, A. Bertolini, A. Ardizzoia, C. Cimminiello
Journal: Journal of Clinical Oncology (2004)

8239 Background: the use of CVD is continuously increasing in oncologic patients due to a number of advantages in terms of quality of life and safety. However several questions remain still unresolved including the true rate of complications related to these devices. To better clarify the issue we planned an observational prospective study on CVD use, called “Registro CVD - PoloNord”, collecting all patients (pts) having placed a CVD, in the PoloNord Group Oncology Services. Methods: starting from January 2003, 19 centers participated to the survey with the aim to follow-up their patients, every four month, for a total of three years. All pts data were collected in a computer-assisted log, running into a web server technology. CVD model, patient medical history and relationships with drug therapy including antithrombotic prophylaxis, CVD related adverse events, thromboembolic events and patient outcome were recorded. Results: so far 504 pts were recruited, the majority of them having advanced disease. There were 250 pts followed-up for at least the first four months; of them 105 (42%) were given an antithrombotic prophylaxis which was represented mainly by low-dose warfarin. We observed 29 (11%) CVD-related complications: 4 misplacements, 6 infections, 5 catheter ruptures, 3 disconnections, 1 occlusion, 9 catheter thrombosis, 1 thoracic decubitus. Furthermore we noticed 23 (9%) thromboembolic events: 2 pulmonary embolisms, 16 deep venous thrombosis and 5 superficial thromboflebitis. The mean follow-up period was 8.5 months. The median time to the first occurring CVD-related complication and thromboembolic event was 185 and 40 days respectively . Conclusions: there is still uncertainty on the need of antithrombotic prophylaxis in pts with a CVD, because of the conflicting data existing on the true rate of thromboembolic complications. By means of survey and registers such as our study we hope to better understand this issue on the basis of clinical practice-based observation. No significant financial relationships to disclose.
The Pediatrician's Dilemma: Respecting Parental Autonomy Versus Protecting Vulnerable Children
Authors: Michael R. Gomez, Kyle J. Bielefeld, Michelle K. Escala, Ric T. Munoz, Mark D. Fox
Journal: The American Journal of Bioethics (2016)

"The Pediatrician's Dilemma: Respecting Parental Autonomy Versus Protecting Vulnerable Children." The American Journal of Bioethics, 16(1), pp. 22–23
Biomarker analyses from the phase III placebo-controlled SATURN study of maintenance erlotinib following first-line chemotherapy for advanced NSCLC
Authors: W. Brugger, N. Triller, M. Blasinska-Morawiec, S. Curescu, R. Sakalauskas, G. Manikhas, J. Mazieres, R. Whittom, K. Rohr, F. Cappuzzo
Journal: Journal of Clinical Oncology (2009)

8020 Background: The SATURN (BO18192) study investigated whether erlotinib maintenance therapy improved PFS in patients (pts) with advanced NSCLC who had obtained clinical benefit from 1st-line chemotherapy. This study included a prospective analysis of the prognostic/predictive value of several molecular markers. Methods: 889 pts with advanced NSCLC whose disease had not progressed following 4 cycles of 1st-line platinum-doublet chemotherapy were randomized to erlotinib 150 mg/day or placebo. Mandatory tumor specimens were collected at baseline and tested for EGFR protein expression using immunohistochemistry (IHC), EGFR gene copy number using fluorescent in-situ hybridization (FISH), and EGFR and KRAS somatic mutations using DNA sequencing. Pts were stratified according to EGFR IHC status (any membranous staining in ≥10% tumor cells used as cut-off); the co-primary endpoint was PFS in EGFR IHC+ pts. Baseline whole blood samples were obtained for genotyping of EGFR (intron 1 CA-repeat polymorphisms). Results: In the overall population, erlotinib significantly prolonged PFS vs placebo (HR 0.71, p&lt;.0001; primary endpoint). The co-primary endpoint was also met, with erlotinib significantly improving PFS in the EGFR IHC+ group (HR 0.69, p&lt;.0001). Many tumor samples were assessable for molecular marker status (see table). Biomarker data suggest that patients derived a PFS benefit with erlotinib irrespective of EGFR FISH or EGFR intron 1 CA-repeat status. The magnitude of benefit with erlotinib was similar in both KRAS-mutant and KRAS wild-type pts. Conclusions: This is the largest biomarker analysis performed for erlotinib in a randomized, placebo-controlled setting, and answers key scientific questions regarding the prognostic and predictive value of potential biomarkers of efficacy. Full data will be presented. [Table: see text] [Table: see text]
Interaction between route of intra-CSF chemotherapy administration and efficacy of therapy in patients wtih neoplastic meningitis
Authors: M. J. Glantz, M. C. Chamberlain, T. Batchelor, W. Eric, F. Cavalli, W. R. Shapiro
Journal: Journal of Clinical Oncology (2006)

1530 Background: NM is a devastating complication of solid tumor and hematologic malignancies. Although controversial, the current standard of care for patients with this disease includes intra-CSF chemotherapy. The importance of route of chemotherapy administration, however, remains controversial. Methods: 124 patients with NM from solid tumors (100 patients) or lymphoma (24 patients) were randomized to receive either sustained-release cytarabine—the study arm; or conventional intra-CSF chemotherapy (methotrexate for solid tumor patients; non-sustained-release cytarabine for lymphoma patients)—the control arm. The route of administration (lumbar vs. ventricular) was not specified. Results: Patients in the study and control arms were well-balanced for factors of known prognostic importance, including age, KPS, and extent of systemic tumor. Progression-free survival was identical between the study and control treatment arms for all patients (35 vs. 43 days, p = 0.73), for solid tumor patients alone (35 vs. 37.5 days, p = 0.79), and for lymphoma patients alone (34 vs. 50 days, p = 0.82). When outcome was examined in solid tumor patients as a function of route of chemotherapy administration, there was no difference in progression-free survival for patients treated with DepoCyt by the ventricular vs. lumbar routes (29 vs. 43 days, p = 0.35). For patients treated with methotrexate, there was a statistically significant difference favoring patients receiving intraventricular therapy (43 vs. 19 days, p = 0.048). Conclusions: Both the pharmacokinetic profile of the intra-CSF chemotherapeutic agent and the site of administration influence the outcome of patients treated for NM. Intraventricular administration, or the use of sustained-release chemotherapeutic agents if the lumbar route is used, appears to be critical to the success of treatment. The implications of this finding may also extend to patients (e.g. those with acute leukemias, high-risk NHL, or her2/neu-positive breast cancer) receiving prophylactic intra-CSF chemotherapy since, in the prophylactic setting, intra-lumbar chemotherapy administration is almost always employed. [Table: see text]
Hepatic Epithelioid Hemangioendothelioma in a Patient With Hemochromatosis
Authors: Nisar Ahmad, Denise M. Adams, Jiang Wang, Rajan Prakash, Nagla Abdel Karim
Journal: Journal of the National Comprehensive Cancer Network (2014)

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare hepatic vascular tumor that represents a diagnostic challenge. The rarity of this neoplasm precludes establishment of a standard-of-care treatment. Risk factors for HEHE are not well-known. Liver transplant remains the most common therapeutic modality for nonmetastatic disease. This article describes a patient who presented with abdominal pain, fatigue, poor appetite, and weight loss. Genetic testing showed that the patient was homozygous for C282Y consistent with hereditary hemochromatosis, and liver biopsy was consistent with malignant epithelioid hemangioendothelioma. The patient was referred for a liver transplant but was deemed inappropriate for transplant secondary to peritoneal studding, with frozen-section analysis showing metastatic disease at the time of surgery.
Preclinical efficacy evaluation of ixabepilone (BMS-247550) in combination with cetuximab or capecitabine in human colon and lung carcinoma xenografts
Authors: F. Y. Lee, A. Camuso, S. Castenada, C. Flefleh, I. Ingio, D. Kan, K. McGlinchey, K. Menard, W. Rose
Journal: Journal of Clinical Oncology (2006)

12017 Background: Ixabepilone belongs to a class of structurally novel, microtubule-stabilizing agents that exert their antimitotic action by binding to tubulin with a binding mode that is distinct from the taxanes. Preclinical findings that ixabepilone has antitumor activity in a broad spectrum of tumor types, including taxane-resistant tumors, is borne out by Phase II clinical trials where ixabepilone has demonstrated activities in multiple tumor types including breast, renal, pancreatic, prostate and lymphoma. The aim of this series of studies was to further characterize the therapeutic potential of ixabepilone in combination with currently approved chemotherapy agents. Methods: Antitumor activity was evaluated in the GEO human colon and L2987 human lung carcinoma xenografts. Therapeutic synergism of the combination was defined as the attainment of efficacy that was significantly better than the best response of the individual single agents administered at their maximum-tolerated dose (MTD) or optimal dose (OD). Results: In the GEO tumors, single-agent ixabepilone produced 1.1 log cell kill (LCK) at its MTD. Cetuximab at its OD yielded 0.8 LCK. The combination of ixabepilone and cetuximab produced 1.7 LCK which was significantly superior to ixabepilone alone (P=0.0173) and cetuximab alone (P=0.0002). Similar synergistic efficacy was observed in the L2987 tumors. The combined efficacy of capecitabine plus ixabepilone was evaluated in the GEO tumors. In this tumor, single-agent ixabepilone was modestly active (LCK = 0.8) at its MTD. Single-agent capecitabine was not effective (LCK = 0.4) at its MTD. However, the combination of the two agents produced therapeutic synergism, yielding antitumor efficacy (1.9 LCK) that was superior to either of the agents alone at their MTDs (P=0.035 and 0.0004, respectively). Conclusions: Ixabepilone demonstrates robust synergistic antitumor efficacy when used in combination with cetuximab or capecitabine in human xenografts providing a biologic rationale for these combinations in the treatment of cancer. [Table: see text]