tbuckley/cabot-search huggingface dataset:
Phase I study of the checkpoint kinase 1 inhibitor GDC-0575 in combination with gemcitabine in patients with refractory solid tumors
Authors: A. Italiano, J.R. Infante, G.I. Shapiro, K.N. Moore, P.M. LoRusso, E. Hamilton, S. Cousin, M. Toulmonde, S. Postel-Vinay, S. Tolaney, E.M. Blackwood, S. Mahrus, F.V. Peale, X. Lu, A. Moein, J. Epler, K. DuPree, M. Tagen, E.R. Murray, J.L. Schutzman, J.O. Lauchle, A. Hollebecque, J.-C. Soria
Journal: Annals of Oncology (2018)

Checkpoint kinase 1 (Chk1) inhibition following chemotherapy-elicited DNA damage overrides cell cycle arrest and induces mitotic catastrophe and cell death. GDC-0575 is a highly-selective oral small-molecule Chk1 inhibitor that results in tumor shrinkage and growth delay in xenograft models. We evaluated the safety, tolerability, and pharmacokinetic properties of GDC-0575 alone and in combination with gemcitabine. Antitumor activity and Chk1 pathway modulation were assessed.In this phase I open-label study, in the dose escalation stage, patients were enrolled in a GDC-0575 monotherapy Arm (1) or GDC-0575 combination with gemcitabine Arm (2) to determine the maximum tolerated dose. Patients in arm 2 received either i.v. gemcitabine 1000 mg/m2 (arm 2a) or 500 mg/m2 (arm 2b), followed by GDC-0575 (45 or 80 mg, respectively, as RP2D). Stage II enrolled disease-specific cohorts.Of 102 patients treated, 70% were female, the median age was 59 years (range 27-85), and 47% were Eastern Cooperative Oncology Group PS 0. The most common tumor type was breast (37%). The most frequent adverse events (all grades) related to GDC-0575 and/or gemcitabine were neutropenia (68%), anemia (48%), nausea (43%), fatigue (42%), and thrombocytopenia (35%). Maximum concentrations of GDC-0575 were achieved within 2 hours of dosing, and half-life was ∼23 hours. No pharmacokinetic drug-drug interaction was observed between GDC-0575 and gemcitabine. Among patients treated with GDC-0575 and gemcitabine, there were four confirmed partial responses, three occurring in patients with tumors harboring TP53 mutation. Pharmacodynamic data were consistent with GDC-0575 inhibition of gemcitabine-induced expression of pCDK1/2.GDC-0575 can be safely administered as a monotherapy and in combination with gemcitabine; however, overall tolerability with gemcitabine was modest. Hematological toxicities were frequent but manageable. Preliminary antitumor activity was observed but limited to a small number of patients with a variety of refractory solid tumors treated with GDC-0575 and gemcitabine.NCT01564251.
Impact of tumor location on the efficacy of first-line anti-EGFR monoclonal antibody plus chemotherapy in patients (pts) with metastatic colorectal cancer (mCRC): Retrospective analyses of the randomized MACRO-2 and PLANET trials from TTD Group
Authors: M. Benavides, A. Carrato, A. Abad, C. Guillen-Ponce, P. Garcia-Alfonso, S. Gil, M.T. Cano Osuna, M.J. Safont, C. Gravalos, J.L. Manzano-Mozo, A. Sanchez, J. Alcaide-Garcia, R. López, B. Massuti Sureda, J. Sastre, E. Martinez de Castro, P. Escudero, M. Méndez-Ureña, E. Diaz Rubio, E. Aranda Aguilar
Journal: Annals of Oncology (2017)
Using Magee equations to predict Oncotype DX recurrence scores: A potential cost and time saving strategy?
Authors: Khalid Salim Al-Baimani, Stephanie Petkiewicz, Xinni Song, Gregory Russell Pond, Mark J. Clemons, Susan Robertson
Journal: Journal of Clinical Oncology (2014)

e22109 Using Magee equations to predict OncoDx Recurrence Scores - a potential cost and time saving strategy? Khalid Al-Baimani1MD, Stephanie Petkiewicz2 MD, Xinni Song3 MD, Gregory Pond4 PhD, Mark Clemons5 MD, Susan Robertson6 MD Background: The three Magee equations incorporate readily available tumor characteristics (i.e. tumor size; grade, ER, PR, Her2, Ki-67)(see table) to formulate a score that correlate with OncoDx Recurrence Scores (ODX). However, Magee equations require the pathologist to perform impractical H scores of ER & PR. We evaluated Magee equations using a surrogate H score based on Allred range and average intensity. This could reduce the number of specimens sent for ODX, saving both time and money. Methods: Magee scores were calculated using surrogate H score for 118 patients with available ODX results. Correlation and discordance rates were calculated. Results: Of the 118 patients; 62 (52.5%) were low-risk, 49 (41.5%) were intermediate and 7 (5.9%) were high-risk. None of the low Magee risk scores were high risk by ODX. None of the Magee high-risk scores were low risk by ODX. Conclusions: This study would suggest that the Magee 2 & 3 equations (using the modified H score based on Allred) could be used in low and high risk cases to avoid performing ODX-RS, saving considerable time and money. The intermediate scores with both Magee and ODX remain a therapeutic challenge. Larger confirmatory studies are needed. Discordance between Magee and ODX-RS scores. Magee score number (n) Discordance with ODX-RS % (95% CI) Magee 1: (tumor size, grade, ER, PR, Her2, Ki-67) Low-risk (<18) n=43 9.3 (2.6%-22.1%) Intermediate-risk (18-31) n=69 36.2 (25.0%-48.7%) High-risk (>31) n=6 16.7 (0.4%-64.1%) Magee 2: (tumor size, grade, ER, PR, Her2 without Ki-67) Low-risk (<18) n=37 16.2 (6.2%-32.0%) Intermediate –risk (18-31) n=78 44.9 (33.6%-56.6%) High-risk (>31) n=3 0 (0.0%) Magee 3: (ER, PR, HER2, and Ki-67 without tumor size or grade) Low-risk (<18) n=52 19.2 (9.6%-32.5%) Intermediate-risk (18-31) n=65 40 (28.0%-52.9%) High-risk (>31) n=1 0 (0.0%)
Reactive stroma mediates CD8+ T cell spatial distribution and function in ovarian cancer
Authors: Y. Wang, L. Ryner, A.R. Udyavar, M. Desbois, C. Kozlowski, C-W. Chang, Y. Guan, S. Lu, H. Koeppen, J. Ziai, R. Bourgon, P.S. Hegde
Journal: Annals of Oncology (2017)
Preoperative chemotherapy and radiotherapy concomitant to cetuximab in stage IIIB NSCLC: A multicenter phase II SAKK
Authors: A. Curioni-Fontecedro, H.-B. Ris, A. Xyrafas, H. Bouchaab, H. Gelpke, N. Mach, O. Matzinger, N. Stojcheva, M. Frueh, R. Cathomas, S. Berardi Vilei, L. Bubendorf, M. Pless, D. Betticher, S. Peters
Journal: Annals of Oncology (2017)
Benefits of upfront primary tumour resection (UPTR) according to sidedness in mCRC: Retrospective analyses of TTD MACRO-2 and PLANET randomised trials
Authors: M. Benavides, A. Abad, A. Carrato, C. Gravalos, A. Fernández-Montes, E. Falcó, E. González-Flores, T. Garcia Garcia, J.I. Martin-Valades, J. Gallego Plazas, M. Valladares-Ayerbes, C. García-Girón, R. Dueñas, A. García-Tapiador, C. Pericay, F. Losa, A. Viudez, P. García-Teijido, E. Diaz Rubio, E. Aranda Aguilar
Journal: Annals of Oncology (2017)
FAK-PD1: a phase I/IIa trial of FAK (defactinib) & PD-1 (pembrolizumab) inhibition
Authors: S. Symeonides, T.R.J. Evans, V. Coyle, A. Serrels, F. Thomson, D. Currie, S. Dillon, J. Paul, D.A. Fennell, C. Ottensmeier
Journal: Annals of Oncology (2017)
Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial
Authors: Paul E Holtzheimer, Mustafa M Husain, Sarah H Lisanby, Stephan F Taylor, Louis A Whitworth, Shawn McClintock, Konstantin V Slavin, Joshua Berman, Guy M McKhann, Parag G Patil, Barry R Rittberg, Aviva Abosch, Ananda K Pandurangi, Kathryn L Holloway, Raymond W Lam, Christopher R Honey, Joseph S Neimat, Jaimie M Henderson, Charles DeBattista, Anthony J Rothschild, Julie G Pilitsis, Randall T Espinoza, Georgios Petrides, Alon Y Mogilner, Keith Matthews, DeLea Peichel, Robert E Gross, Clement Hamani, Andres M Lozano, Helen S Mayberg
Journal: The Lancet Psychiatry (2017)
Authors reply: Prevention of the spread of infection – the need for a family-centred approach to hygiene promotion
Authors: S Bloomfield, M Exner, G  M Fara, E A Scott
Journal: Eurosurveillance (2008)

We agree that promulgating the hygiene hypothesis and related environmental issues to the public can serve to confuse, rather than to inform. The reality is however that these issues have already received widespread coverage by the media, which tends to leave the public concerned and confused about the role of hygiene and cleanliness, particularly in relation to the functioning of the immune system.
Diagnostic and therapeutic strategies for elderly patients with advanced non-small cell lung cancer (NSCLC): Results from an EORTC pan-European survey
Authors: M. Giaj Levra, J. Menis, A. Luciani, E. De Maio, B. Hasan, T. Berghmans, M.A. Massiani, M. De Waele, A.-M. Dingemans, J. Donckele, C. Faivre-Finn, N. Girard, L. Greillier, S. Lantuéjoul, M. O'Brien, M. Reck, K. Tryfonidis, H. Wildiers, B. Besse, S. Novello
Journal: Annals of Oncology (2017)
Cloning, expression, purification and characterization of the human class Ia phosphoinositide 3-kinase isoforms.
Authors: Timothy I. Meier, James A. Cook, James E. Thomas, Jeffrey A. Radding, Candice Horn, Trupti Lingaraj, Michele C. Smith
Journal: Cancer Research (2004)

3524   The Class I Phosphoinositide 3 –Kinases (PI3Ks) are lipid kinases that phosphorylate the 3-hydroxyl group of the inositol ring of phosphatidylinositides. Although closely related, experimental evidence suggests that the four Class I PI3Ks may be functionally distinct. In order to identify their unique kinetic parameters, the three human Class Ia PI3K (α, β, δ) p110 catalytic domains were cloned and co-expressed with the p85α regulatory domain in Sf9 cells. None of the p110 subunits were successfully expressed in the absence of p85α. Successful expression and purification of each p85α/p110 protein required using an excess of the p110 vector over the p85 vector during co-infection of Sf9 cells. Proteins were purified as the p85α/p110 complex by nickel affinity chromatography through an N-terminal His-tag on the p110 subunit using an imidazole gradient. The identity of each purified isoform was confirmed by mass spectral analysis and immunoblotting. The kinetics of the three p85α/p110 proteins, the Class Ib p110 γ catalytic domain, and bovine PI3K were investigated using phosphatidylinositol 4,5-bisphosphate (PIP2) as the substrate in a PIP2/Phosphatidylserine (PS) liposome. All five enzymes exhibited reaction velocities that were dependent on the surface concentration of PIP2. The maximal activity for each human isoform was obtained at PIP2 concentrations ranging from 2.5 mol % PIP2 for p110γ to 10 mol % PIP2 for p85α/p110α. The specific activity of p85α/p110α was three to five times higher than the other human isoforms. These kinetic differences may contribute to the unique roles of these isoforms in cells.
Compounded Bioidentical Hormone Therapy
Authors: Cynthia A. Stuenkel, JoAnn E. Manson
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Nonpharmacologic Treatments for Depression in Older Adults—Reply
Authors: Rob M. Kok, Charles F. Reynolds
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Efficacy of pembrolizumab in phase 2 KEYNOTE-164 and KEYNOTE-158 studies of microsatellite instability high cancers
Authors: L. Diaz, A. Marabelle, T.W. Kim, R. Geva, E. Van Cutsem, T. André, P.A. Ascierto, M. Maio, J-P. Delord, M. Gottfried, R. Guimbaud, D. Jaeger, E. Elez, T. Yoshino, A. Joe, B. Lam, J. Ding, S. Pruitt, S.P. Kang, D.T. Le
Journal: Annals of Oncology (2017)
Métodos para a vigilância virológica sentinela da gripe na Europa, um estudo sobre 18 países
Authors: T J Meerhoff, A Meijer, W J Paget
Journal: Eurosurveillance (2004)

O programa europeu de vigilância da gripe (European Influenza Surveillance Scheme, EISS) esta baseado num modelo itegrado de vigilância clinica e virologica. Para avaliar a comparabilidade dos dados virologicos, foi enviado um questionario aos participantes em Junho 2002 sobre a colheita de amostras, o diagnostico laboratorial da gripe e os testes para outras infeccoes respiratorias. 
Os resultados mostraram diferencas mas tambem uma certa uniformidade quanto aos metodos de recolha de dados virologicos. Ao nivel dos procedimentos de colheita de amostras foram encontradas semelhancas; o tipo de esfregacos e as condicoes de transporte eram comparaveis. Os metodos de diagnostico eram diferentes; notaram-se diferencas nos metodos de sub-tipagem, sendo o PCR o mais utilizado nos paises da Europa ocidental. Os resultados serao uteis na interpretacao dos dados virologicos colhidos pelos medicos sentinela e para a criacao de uma rede Comunitaria de Laboratorios de Referencia para a Gripe na Europa. Alguns dos principais objectivos desta rede Comunitaria incluem a harmonizacao dos metodos virologicos e a aplicacao do programa de controlo de qualidade dos Laboratorios Nacionais de Referencia.
Benefits of Abiraterone Acetate Plus Prednisone (AA+P) When Added to Androgen Deprivation Therapy (ADT) in LATITUDE on Patient (Pt) Reported Outcomes (PRO)
Authors: K. Chi, A. Protheroe, A. Rodriguez Antolin, G. Facchini, H. Suttmann, N. Matsubara, Z-Q. Ye, B. Keam, T. Li, K. McQuarrie, B. Jia, P. De Porre, J. Martin, M.B. Todd, K. Fizazi
Journal: Annals of Oncology (2017)
Abstract 20186: Argon Postconditioning Decreases Ischemia/Reperfusion-Induced Ventricular Fibrillation in Rat Isolated Hearts
Authors: Hunter F Douglas, Michele M Salzman, Timothy R Matsuura, Jason A Bartos, Tom P Aufderheide, Demetris Yannopoulos, Matthias L Riess
Journal: Circulation (2016)

Introduction:  Ventilation with the noble gas Argon subsequent to cardiac arrest and cardiopulmonary resuscitation (CPR) has been demonstrated to enhance hemodynamic and neurologic outcome in rats and pigs.   Hypothesis:  We hypothesized that the cardioprotective effective of Argon remains intact in rat isolated hearts when administered as a postconditioning agent immediately upon reperfusion (R) following global myocardial ischemia (I).   Methods:  Twenty-one Langendorff-prepared hearts from Brown Norway rats were perfused for 35 minutes with Krebs solution saturated with 30% O2, 65% N2, 5% CO2 gas mixture and subjected to 25 minutes I followed by 120 minutes R. Left ventricular electrocardiogram, pressure, and coronary flow were recorded before, during and after I/R. Infarct size (IS) was measured by TTC staining at the conclusion of the experiment. Hearts were randomized to one of three groups: the control group was reperfused with 30% O2, 65% N2, 5% CO2 gas mixture, while Argon treated hearts received 30% O2, 65% Argon, 5% CO2 gas mixture for the first 10 minutes of reperfusion only or the entire 120 minutes of reperfusion following global ischemia. Statistics: chi square and ANOVA followed by SNK; alpha 0.05.   Results:  We observed no statistical differences between the three groups in functional outcome or IS, but found a significant decrease in the occurrence of ventricular fibrillation in the 10-minute Argon treated hearts (1/7) and 120-minute Argon treated hearts (2/7) requiring cardioversion by lidocaine administration compared to control hearts (7/7).   Conclusion:  Our results indicate that, in contrast to previous in vivo studies of global I/R, Argon, when given as a postconditioning agent immediately upon reperfusion, does not attenuate I/R injury at the isolated organ level, but appears to require mechanisms present in vivo to improve cardiac function. A reduced occurrence of ventricular fibrillation with improved perfusion of vital organs, however, may contribute to the observed cardioprotective and neuroprotective effects during and after CPR in vivo.
33 A case-control study comparing primary non-responders and responders to infliximab therapy in inflammatory bowel disease patients
Authors: R Khan, A Keogh, JM Lee, L Egan
Journal: Gut (2017)

Background  Infliximab has been successfully used for the treatment of IBD for many years. However, treatment failures are common. Primary non-response was reported to occur in 13%–14% of patients in clinical trials. Therefore the early identification of non-response and timely switch to another agent, dose adjustment is of paramount importance.  Aim  In literature, there is very little known about primary non-response to infliximab. Most of the studies done in the past are based on loss of response or emergence of anti-infliximab antibodies. No such single study exists in the literature.  Method  Total 218 patients records were searched. Out of 218, only 20 were included as cases. The inclusion criteria was either Crohns or Ulcerative colitis patient who were primary non-responders. Primary non-response was defined as all those patients who fail to respond to the standard induction doses of infliximab. Another 20 subjects were selected from the same pool as controls and were matched with cases in terms of age, sex and disease type.  This study was analysed using EPI-INFO STATCALC software from the CDC.gov.  Results  Odds ratios were calculated using the 2by2 tables for matched-pair case control study.1. Smoking was associated with primary non-response and the OR was 2.33 with 95% CI. Similarly, in this study, there was a trend of primary non-response with low levels of CRP at the time of start of therapy with the odds ratio of 0.25 (95% CI) and p-value 0.054. The odds for albumin, weight and Haemoglobin were 0.8,0.42 and 0.33 respectively and their p-values did not reach significance due to small sample size.  Conclusions  From this study, there is a trend towards primary non-response to infliximab if a patient is a smoker with low levels of CRP at the time of initiation of therapy. Further studies with large sample size are needed to study the clinical significant association between haemoglobin, Albumin, and weight of the patients at the time of initiation of therapy.
The longevity gene INDY ( I 'm N ot D ead Y et) in metabolic control: Potential as pharmacological target
Authors: Diana M. Willmes, Anica Kurzbach, Christine Henke, Tina Schumann, Grit Zahn, Alexander Heifetz, Jens Jordan, Stephen L. Helfand, Andreas L. Birkenfeld
Journal: Pharmacology & Therapeutics (2017)

The regulation of metabolic processes by the Indy (I′m Not Dead Yet) (SLC13A5/NaCT) gene was revealed through studies in Drosophila melanogaster and Caenorhabditis elegans. Reducing the expression of Indy in these species extended their life span by a mechanism resembling caloric restriction, without reducing food intake. In D. melanogaster, mutating the Indy gene reduced body fat content, insulin-like proteins and reactive oxygen species production. Subsequent studies indicated that Indy encodes a citrate transporter located on the cell plasma membrane. The transporter is highly expressed in the mammalian liver. We generated a mammalian knock out model deleting the mammalian homolog mIndy (SLC13A5). The knock out animals were protected from HFD induced obesity, fatty liver and insulin resistance. Moreover, we have shown that inducible and liver selective knock down of mIndy protects against the development of fatty liver and insulin resistance and that obese humans with type 2 diabetes and non-alcoholic fatty liver disease have increased levels of mIndy. Therefore, the transporter mINDY (NaCT) has been proposed to be an 'ideal target for the treatment of metabolic disease'. A small molecule inhibitor of the mINDY transporter has been generated, normalizing glucose levels and reducing fatty liver in a model of diet induced obese mice. Taken together, studies from lower organisms, mammals and humans suggest that mINDY (NaCT) is an attractive target for the treatment of metabolic disease.
Autologous Stem Cell Transplant (ASCT) Improves the Prognosis of AL Amyloidosis By Inducing a Higher Organ Response Rates and May be Preferred As First Line Treatment Both in AL and in AL Associated with Multiple Myeloma (MM)
Authors: Angelo Belotti, Rossella Ribolla, Claudia Crippa, Vincenza Orlando, Mariella D'Adda, Alessandro Re, Enrico Morello, Chiara Cattaneo, Giuseppe Rossi
Journal: Blood (2016)
Phase I study of NRC-an-019, a tyrosine kinase inhibitor, in imatinib-resistant chronic myeloid leukemia (CML) in an Indian tertiary care hospital.
Authors: Raghunadharao Digumarti, Praveen Chowdary Myneni, Venkata Ramana Gogula, Srihari Uppalapati, Sangeeta Premchand Jiwatani
Journal: Journal of Clinical Oncology (2013)

7080 Background: NRC-AN-019 is an orally administered tyrosine kinase inhibitor (TKI) of the Bcr-Abl protein-tyrosine kinase. The drug was given to patients as a ready-to-use liquid formulation. Methods: The primary objectives of the Phase-I study were to estimate the Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD) of NRC-AN-019 and also to establish the safe dose for Phase II clinical trial. The secondary objectives were to study the pharmacokinetic properties and antileukemic activity of NRC-AN-019. Philadelphia positive CML patients in all phases, in the age group of 18-65 years were eligible. They had to be resistant or intolerant to Imatinib, with ECOG ≤ 2. Dosing was initiated at 50 mg/day and dose escalation was done in increments of 50 mg per each additional cohort. The maximum dose administered was 450 mg/day. The protocol-specific study duration was 30 days; patients continued to receive the study drug subsequently based on Investigator’s decision. Results: A total of 30 patients were enrolled (3 at 50 mg, 4 at 100 mg, 3 at 150 mg, 3 at 200 mg, 4 at 250 mg, 4 at 300 mg, 3 at 350 mg, 3 at 400 mg, and 3 at 450 mg). DLT was not observed and MTD was not reached. The recommended Phase II-A dose is 300 mg/day, with a scope for escalation up to 450 mg/day. The maximum plasma concentration of NRC-AN-019 was 9,342 ng/mL and AUC was 1,262,191 ng.hr/mL. Common adverse events were skin rash, nausea, and vomiting. Hematological response was observed in 11 patients, cytogenetic response in 7 patients and molecular response in 5 patients. The maximum duration a patient has been on NRC-AN-019 is 863 days. Conclusions: Based on the Phase-I data, NRC-AN-019 showed considerable safety and response; it could be a potential treatment option for imatinib-resistant CML. Clinical trial information: CTRI/2009/091/000204.