tbuckley/cabot-search huggingface dataset:
Non-pegylated liposomal doxorubicin and docetaxel as front line treatment in HER2-neu negative metastatic breast cancer: Safety and efficacy results
Authors: L. Cals, P. Nouyrigat, X. Tchiknavorian, N. Dohollou, F. Bertrand, C. Bressac, P. Gomez, T. Facchini, M. Besset, J. Gligorov
Journal: Journal of Clinical Oncology (2006)

10659 Background: First line docetaxel (D) and doxorubicin (DXR) yield up to 55% response rates in controlled studies, in relapse situation for patients who have received anthracyclin in adjuvant setting, with the risk to run on cardiotoxicity regarding anthracyclin cumulative dose.The objective of the study is to determine efficacy and tolerance of Myocet (M) and D as frontline chemotherapy in her2-neu negative metastatic breast cancer (MBC) patients (pts) who have received anthracyclin in adjuvant setting. Methods: Eligible pts were above 18 years, with MBC relapsing at least 12 month after anthracyclin given in adjuvant setting. WHO = 0–1-2, normal left ejection fraction (LEF), measurable targets, cumulative dose of DXR or epirubicin or mitoxantron previously administred respectively under 300, 600, 75 mg/m 2 . Ongoing hormonotherapy or radiotherapy had to be stop at least 4 weeks before treatment: M = 60 mg/m 2 was given as 90 minutes infusion, followed by D = 75 mg/m 2 given as 60 minutes infusion, the both 21 days cycles for 6 cycles. Clinical adverse event review, haematology was performed each cycle, LEF each two cycles, tumor assessment, at day 50 and day 120. Results: Between 04/04 and 05/05: 21 pts with median age 55 (33–72) entered the study. All pts were metastatic (liver 10 pts, bone 9, lung 4, soft tissue 2, skin 2, pleural 1, multiples 6). Premenopausal 6 pts , negative oestrogen receptor: 5 pts. A total of 108 MD infusion has been given, infusions delayed 11, omitted 1, reduced dose 15. Use of neutrophils growth factors 11 pts. No treatment related death has been reported. Grade 3/4 toxicity: febrile neutropenia 6 pts (28%), thrombocytopenia 1, alopecia 21, nausea-vomiting 0, gastritis 1, dental infection 1, one cardiac heart failure grade 3 was observed 6 month after the end of 9 cycles of MD, responsive to angiotensin conversion inhibitor. Efficacy: 10 partials responses, 5 completes responses and 2 progressive disease. RR = 71% Binomial 95% CI (53–85). Conclusions: MD is clinically well tolerated with however 28 % grade 3/4 neutropenia and a large use of neutrophils growth factors, no life threatening aplasia was observed. The high response rate had to be confirm with the safety results at the end of the accrual (50 pts planed). No significant financial relationships to disclose.
Population PK/PD analysis of the pan-HDAC inhibitor resminostat.
Authors: Roland Baumgartner, Stefan W. Henning, Bernhard Hauns, Astrid Ammendola, Babett Krauss, Julia Holzapfel, Michael Bitzer, Bernd Hentsch
Journal: Journal of Clinical Oncology (2014)

e13527 Background: Resminostat, an oral pan-HDAC inhibitor, was investigated in various oncological indications. To investigate pharmacokinetic (PK) and pharmacodynamic (PD) properties of resminostat, a population PK/PD model was established to quantitatively describe the time course of HDAC inhibition. Methods: PK and PD data from a clinical Phase I study in patients with solid tumors were included in the analysis. Single dose PK data of 100 mg, 200 mg, 400 mg, 600 mg and 800 mg dose groups were fitted simultaneously to a two-compartment model. A transit compartment model captured a delayed drug input. Collected PD data comprised pan-HDAC inhibition measured ex vivo in leukocytes of 18 patients using the fluorogenic substrate Boc-K(Ac)-AMC. Deacetylation results in trypsin cleavage and released AMC dye is quantified. Several PD models were explored. Model selection and diagnosis was performed applying information criteria, goodness-of-fit plots and visual predictive checks. Results: Ex vivo measured pan-HDAC inhibition by resminostat could successfully be described by a population PK/PD model. Maximum HDAC inhibition occurs within 2 h after dosing and transiently reaches a maximum > 90% inhibition at dose levels of 600 mg and 800 mg. Half-life (t1/2) of PD response is relatively short per se (≈ 6 h), but still 2-times the terminal t1/2 of PK. HDAC inhibition is described by a receptor on/off model. Derived apparent KDamounts to 454 ± 168 nM, closely matching values from leukocytes spiked with resminostat (570 ± 260 nM). HDAC inhibition was also evaluated in Phase II studies in patients with Hodgkin’s lymphoma or hepatocellular carcinoma. PD characteristics like onset, duration and intensity of response could be confirmed. Simulation of alternative dosing schemes revealed improved target coverage over a 24 h period upon BID dosing. This scheme was implemented in a Phase I/II trial with resminostat in colorectal carcinoma patients, where biomarker dynamics were confirmed. Conclusions: The established model accurately describes the clinical PK/PD relationship of resminostat. The model will be used to inform future trial designs. Ex vivo HDAC inhibition measured in peripheral blood represents a robust PD marker to monitor target engagement.
TREATMENT PATTERNS AND RESOURCE USE OF HEART FAILURE PATIENTS ON MEDICAID IN FIVE STATES IN THE US
Authors: Tzy-Chyi Yu, Jenny Zhou, Dendy Macaulay, Huanxue Zhou, Stuart Turner, Ashok Vegesna, Deborah Goldschmidt, Olivia Liu, James Signorovitch
Journal: Journal of the American College of Cardiology (2017)
THE PREDICTIVE VALUE OF MICROVASCULAR DEFECTS OBSERVED DURING DEMAND STRESS MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY AND QUANTITATIVE MEASUREMENTS OF STENOSIS AND MICROVASCULAR RESISTANCE OBTAINED DURING INVASIVE HEMODYNAMICS
Authors: David Barton, Yiannis Chatzizisis, Feng Xie, Edward O'Leary, Gregory Pavlides, Thomas Porter
Journal: Journal of the American College of Cardiology (2017)
Use of tumor-targeting salmonella typhimurium to eradicate human glioma in an orthotopic model in nude mice.
Authors: Masashi Momiyama, Ming Zhao, Hiroaki Kimura, Benjamin Tran, Takashi Chishima, Michael Bouvet, Itaru Endo, Robert M. Hoffman
Journal: Journal of Clinical Oncology (2012)

2044 Background: Prognosis remains poor for glioma and therefore requires new approaches. We have previously developed a genetically-engineered strain of Salmonella typhimurium, A1-R, that targets tumors without overt toxicity in mouse models (Proc. Natl. Acad. Sci. USA 102, 755-760, 2005; Cancer Research 66, 7647-7652, 2006; Proc. Natl. Acad. Sci. USA 104, 10170-10174, 2007; Expert Opinion on Drug Discovery 7, 73-83, 2012). In the present study, we demonstrated that Salmonella typhimurium A1-R can inhibit and eradicate human glioma in an orthotopic nude mouse model. Methods: S. typhimuirum A1-R was administered by injection through a craniotomy open-window or intravenously in nude mice. To establish the model, 2×10 5 U87 human glioma cells, expressing red fluorescent protein (RFP), were injected stereotactically into the mouse brain through the craniotomy open window. Two weeks after glioma-cell implantation, mice were treated with S. typhimurium A1-R (2×10 7 CFU / 200 μl intravenous injection [i.v.] or 1×10 6 CFU / 1 μl intracranial injection [i.c.]) once a week for 3 weeks. Results: Brain tumors were observed by fluorescence imaging through the craniotomy open window over time. S. typhimurium A1-R, administered i.c., inhibited brain tumor growth 7.6-fold compared with untreated mice (p = 0.009) and improved survival 73% (p = 0.001). Two of ten mice had their tumors eradicated. Intravenous administration of S. typhimurium A1-R was not effective. Conclusions: The results of the present study demonstrate that bacterial therapy of glioma is a novel, effective and safe treatment strategy in a highly treatment-resistance cancer in an orthothopic model, a first step toward clinical development.
Targeting 14-3-3 Sensitizes Native and Mutant BCR-ABL to Inhibition with U0126, Rapamycin and Bcl-2 Inhibitor GX15-070.
Authors: Shaozhong Dong, Sumin Kang, Sagar Lonial, Hanna Jean Khoury, Jean Viallet, Jing Chen
Journal: Blood (2007)
Epidemiology of Adult T-Cell Leukemia/Lymphoma in Martinique (1983-2013): Robustness of Classification of Lymphoma Study Group of Japa, Relevance of Cutaneous Lesions, Atypical Phenotype and Origin of the HTLV-1 Infected Cell
Authors: Yves Plumelle, Rishika Banydeen, jean-Come Meniane, Stephane Michel, Gerard Panelatti, Delaunay Christine
Journal: Blood (2014)
Neurotransmitter Switching in the Developing and Adult Brain
Authors: Nicholas C. Spitzer
Journal: Annual Review of Neuroscience (2017)

Neurotransmitter switching is the gain of one neurotransmitter and the loss of another in the same neuron in response to chronic stimulation. Neurotransmitter receptors on postsynaptic cells change to match the identity of the newly expressed neurotransmitter. Neurotransmitter switching often appears to change the sign of the synapse from excitatory to inhibitory or from inhibitory to excitatory. In these cases, neurotransmitter switching and receptor matching thus change the polarity of the circuit in which they take place. Neurotransmitter switching produces up or down reversals of behavior. It is also observed in response to disease. These findings raise the possibility that neurotransmitter switching contributes to depression, schizophrenia, and other illnesses. Many early discoveries of the single gain or loss of a neurotransmitter may have been harbingers of neurotransmitter switching.
Detection of Hemoglobin (Hb) Variants By HPLC Screening in Cord Blood Units (CBU) Donated to the National Cord Blood Program (NCBP)
Authors: Ludy Dobrila, Tracy Zhu, Dan Zamfir, Michal Tarnawski, Rodica Ciubotariu, Maria S Albano, Maryely DeLeon, Kelsey Turner, Mahin Azimi, Carolyn C. Hoppe, Andromachi Scaradavou, Pablo Rubinstein
Journal: Blood (2016)
REMOTE TELEMONITORING IN CHRONIC HEART FAILURE DOES NOT REDUCE HEALTHCARE COST BUT IMPROVES QUALITY OF LIFE: ENDPOINTS OF THE CARDIOBBEAT TRIAL
Authors: Heinz Voeller, Dominik Bindl, Klaus Nagels, Reiner Hofmann, Eik Vettorazzi, Karl Wegscheider, Eckart Fleck, Eckhard Nagel
Journal: Journal of the American College of Cardiology (2017)
PRESENCE OF POST-SYSTOLIC SHORTENING BY TISSUE DOPPLER IMAGING IS AN INDEPENDENT PREDICTOR OF HEART FAILURE IN PATIENTS FOLLOWING ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION
Authors: Philip Brainin, Sune Pedersen, Morten Sengeløv, Flemming Javier Olsen, Thomas Hansen, Jan Jensen, Tor Biering-Sorensen
Journal: Journal of the American College of Cardiology (2017)
DETERMINATION OF THE IDEAL CONTACT FORCE REQUIRED DURING PULMONARY VEIN ANTRUM ISOLATION (PVAI)
Authors: Pouria Alipour, Yaariv Khaykin, Zahra Azizi, Meysam Pirbaglou, Sergio Conti, Paul Ritvo, Alfredo Pantano, Atul Verma
Journal: Journal of the American College of Cardiology (2017)
EVALUATION OF RIGHT VENTRICULAR DYSFUNCTION AND PROGNOSIS USING THREE-DIMENSIONAL RIGHT VENTRICULAR WALL MOTION TRACKING IN PATIENTS WITH PULMONARY ARTERY HYPERTENSION
Authors: Konomi Sakata, Aoi Isaka, Youichiro Uesugi, Mitsufumi Furuya, Mayumi Fukushima, Kenichi Matsushita, Toru Satoh, Hideaki Yoshino
Journal: Journal of the American College of Cardiology (2017)
COMPARISON OF TWO-YEAR OUTCOMES IN DRUG-ELUTING STENTS VERSUS CORONARY ARTERY BYPASS GRAFTING FOR TREATMENT OF UNPROTECTED LEFT MAIN CORONARY ARTERY DISEASE IN ELDERLY PATIENTS: A META-ANALYSIS
Authors: Wina Yousman, Justin Lee, Wei Xiang Wong, Jarred Sargeant, Carol Howe, Iwan Nyotowidjojo, Ahmed Pasha, David Fortuin, Kwan Lee
Journal: Journal of the American College of Cardiology (2017)
Patterns of Venous Thromboembolism (VTE) Following Monoclonal Gammopathy of Undetermined Significance (MGUS) and Multiple Myeloma (MM) among 4 Million U.S. Veterans.
Authors: Ola Landgren, Thomas R. Fears, Ingemar Turesson, Magnus Bjorkholm, Sigurdur Y. Kristinsson, Gloria Gridley, Neil E. Caporaso
Journal: Blood (2006)
CARDIOMYOPATHY ASSOCIATED WITH TARGETED ANTICANCER THERAPIES IN ELECTRONIC HEALTH RECORDS
Authors: Yan Gong, Hoai Nguyen, Anita Szady, Issam Hamadeh, Gloria Lipori, Qian Sun, Rhonda Cooper-DeHoff, Taimour Y. Langaee, Chintan Shah, Carl Pepine, Alexandra Lucas, Jan Moreb
Journal: Journal of the American College of Cardiology (2017)
PROGNOSTIC IMPACT OF PREMATURE ATRIAL COMPLEXES IN THE GENERAL POPULATION: A META-ANALYSIS OF OBSERVATIONAL STUDIES
Authors: Aashay Patel, Dixitha Anugula, Arun Kanmanthareddy, Prakrity Urja, Toufik Mahfood Haddad, Venkata Alla
Journal: Journal of the American College of Cardiology (2017)
RCP survey highlights workload, morale, and patient safety concerns
Authors: Abi Rimmer
Journal: BMJ (2017)

The Royal College of Physicians has published a report highlighting physicians’ concerns about high workloads, low staff morale, and risks to patient safety.

The report, launched on Thursday 16 March at the college’s annual conference in Manchester, includes the results of a survey of college members conducted online between 9 January and 3 February.1

Of the 2101 physicians who responded to the survey, 55% said …
Hedgehog signalling in primary cervix xenograft (OCICx) models: A potential new therapeutic target in combination with chemoradiotherapy.
Authors: Naz Chaudary, Melania Pintilie, Salomeh Jelveh, Hedley David, Michael Milosevic, Richard P. Hill, Helen Mackay
Journal: Journal of Clinical Oncology (2014)

11120 Background: Overcoming treatment resistance and repopulation in patients undergoing chemo-radiotherapy for primary treatment of cervical cancer is critical in order to improve long-term survival. Upregulation of Hh gene expression in women with cervical cancer prior to chemoradiotherapy is associated with a worse outcome. Aim: to investigate inhibition of the Hh pathway in combination with chemoradiotherapy in orthotopic primary cervical cancer xenograft models (OCICX). Methods: mRNA expression levels of Hh pathway members were characterized using qRT-PCR analysis in OCICx models. To simulate clinical treatment 5E1 (antibody blocking SHH and IHH ligand interaction with PTCH1) was administered to mice bearing cervix xenografts (20 mg/kg/weekly) with localized fractionated irradiation (15 x 2Gy fractions given 5 days/wk over 3 wks). Tumor growth delay, lymph node metastases, survival and toxicity were assessed. Results: The OCICX models exhibited matched levels of Hh gene expression compared to the patient tumor samples. The OCICX models recapitulate the stroma of the orginal tumor. OCICX models with higher tumor to stroma content showed higher human Hh gene expression. Higher mouse Hh gene expression was seen in tumors with more stroma. Combination radiochemotherapy plus 5E1 treatment caused greater growth delay than irradiation or 5E1 alone, reduced lymph node metastasis with increase in survival. No overt toxicity was observed in the mice treated with 5E1 or in combination with radiation. Conclusions: Combination treatment with fractionated irradiation and 5E1 shows increased efficacy consistent with an additive effect. In addition, inhibition of the Hh pathway significantly reduced lymphnode metastasis in the mice. Further investigation of Hh pathway inhibition in combination with chemo-radiotherapy in cervix cancer is warranted including exploration of predictive imaging markers of response.
Adjuvant chemotherapy (AC) outcomes in young (YP) and elderly patients (EP) with high-risk stage II colon cancer (CC).
Authors: Aalok Kumar, Hagen F. Kennecke, Howard John Lim, Daniel John Renouf, Sharlene Gill, Ryan Woods, Caroline Speers, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2013)

3569 Background: High-risk stage II CC is defined as those presenting with T4 stage, obstruction or perforation, &lt;12 lymph nodes retrieved, positive resection margins, and lymphovascular or perineural invasion. Our prior findings suggest that improved outcomes from AC are limited to specific high risk features, such as T4 disease (Kumar et al, ASCO 2012). It is unclear if this benefit is seen across all ages. Our aim was to compare patterns of AC use and outcomes in YP and EP with high risk stage II CC. Methods: All patients diagnosed with high risk stage II CC from 1999 to 2008 and evaluated at any 1 of 5 regional cancer centers in British Columbia were categorized into YP (age &lt;70 years) or EP (age &gt;/=70 years). Kaplan-Meier methods and Cox regression were used to correlate receipt of AC with overall survival (OS), disease specific (DSS) and relapse free survival (RFS), stratified by age group. Results: A total of 1,236 patients were identified: 636 (51%) YP and 600 (49%) EP among whom 363 (57%) and 85 (14%) received AC, respectively. Individuals who received AC in either age group had better performance status than those who did not (ECOG 0/1 47% vs. 34%, p=0.02). After adjusting for known prognostic factors, a significant advantage in OS, but not DSS or RFS, from AC was observed for both YP and EP (Table). The impact of AC on these outcomes was similar across age groups (p interaction of age and treatment = 0.46, 0.64 and 0.69 for OS, DSS and RFS, respectively). In the entire cohort, individuals with T4 lesions had significantly improved OS (HR 0.50, 95%CI 0.33-0.77, p=0.002), DSS (HR 0.59, 95%CI 0.37-0.93, p=0.03), and RFS (HR 0.63, 95%CI 0.42-0.95, p=0.03). The effect of AC in the T4 subgroup was also similar for both YP and EP in terms of OS, DSS and RFS (p interaction of age and treatment = 0.41, 0.71 and 0.77, respectively). Conclusions: In this population-based cohort of high risk stage II CC, improvements in outcomes from AC were seen mainly in those with T4 disease, regardless of age. [Table: see text]
A multi-center randomized controlled trial of mFOLFOX6 with or without radiation in neoadjuvant treatment of local advanced rectal cancer (FOWARC study): Preliminary results.
Authors: Yanhong Deng, Pan Chi, Ping Lan, Lei Wang, Long Cui, Daoda Chen, Jie Cao, Hongbo Wei, Xiang Peng, Zonghai Huang, Guangfu Cai, Ren Zhao, Zhongcheng Huang, Yiding Luo, Yuxin Zhang, Yue Cai, Jianping Wang
Journal: Journal of Clinical Oncology (2015)

3500 Background: The FOWARC study investigates whether peri-operative mFOLFOX6 chemotherapy (CT) improves disease-free survival (DFS) in locally advanced rectal cancer. Methods: Between 01/2011-02/2015, patients with rectal cancer within 12 cm from the anal verge, clinical stage II-III were randomly assigned to received 5-FU with radiation(RT) (control arm), or receive mFOLFOX6 with RT (FOLFOX-RT arm), or receive 4-6 cycles of mFOLFOX6 alone (FOLFOX arm), post-operative RT is allowed if needed. Primary endpoint is DFS. Here we report the preliminary results. Results: 495 patients were randomized (165 in each arm). 92% of patients accomplished at least 46 Gy of RT in FOLFOX-RT arm compared to 86.8% in control arm. 5% of FOLFOX arm patients received post-op RT. R0 resection rate was 90.1%, 88.2%, and 91.2%, respectively in control arm, FOLFOX-RT arm and FOLFOX arm. The pCR rate was 12.5%, 31.3% and 7.4% respectively (P = 0.001). Good down staging (ypTNM 0-1) was achieved in 34.7%, 57.8%, and 37.9% of patients respectively. Higher toxicity and post-op complications were observed in patients received RT. Similar results were seen in subgroup of patients with lesions located within 5cm from the anal verge. Conclusions: mFOLFOX6 concurrent with RT resulted in higher pCR rate, neoadjuvant mFOLFOX6 alone achieved similar down staging rate with less toxicity and post-op complications, compared to preoperative 5-FU with RT. Clinical trial information: NCT01211210. All patients Subgroup(0-5cm) Control FOLFOX-RT FOLFOX Control FOLFOX-RT FOLFOX Age Median(Range) 56.2(24-75) 52.0(27-73) 56.0(21-75) 56.2(24-75) 52.6(30-72) 56(28-73) Clinical T4b(%) 8.6 8.6 3.0 11.1 8 4.8 Clinical staging III (%) 76.5 75 70.3 67.9 66.7 51.3 pCR(%) 12.5 31.3 7.4 14.3 43.2 8.8 ypTNM 0-I(%) 34.7 57.8 37.9 33.3 62.1 41.2 TRG 0-1(%) 33.2 65.6 38.5 33.3 52 26.1 R0 resection (%) 90.1 88.2 91.2 72.2 74 76.2 Sphincter preservation (%) 76.5 82.8 88.2 59.3 62 66.7 Grade 3/4 Leucopenia(%) 14.8 20.9 7.9 15.1 14.6 15.8 Grade 3/4 radiodermatitis(%) 13.6 20.0 - 17 20.8 - Grade 3/4 radiation proctitis(%) 9.8 13.2 - 13.1 10.4 - Anastomotic leakage(%) 24.3 18.8 6.3 20 18.4 3 Infection of incision (%) 25.7 29.9 9.5 30.8 39.5 9.1
Phase III AXIS trial of axitinib versus sorafenib in metastatic renal cell carcinoma: Updated results among cytokine-treated patients.
Authors: M. Dror Michaelson, Brian I. Rini, Bernard J. Escudier, Joseph Clark, Bruce Redman, Jamal Christo Tarazi, Brad Rosbrook, Sinil Kim, Robert John Motzer
Journal: Journal of Clinical Oncology (2012)

4546 Background: Axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, improved progression-free survival (PFS) compared to sorafenib in patients with metastatic renal cell carcinoma (mRCC) in the phase III AXIS trial. In patients previously treated with cytokines, median PFS (mPFS) was 12.1 mo. In a prior phase II study of axitinib for cytokine-refractory mRCC, mPFS was 13.7 mo and the 5-yr overall survival (OS) rate was 20.6%. We report updated PFS and OS for cytokine-treated patients from the AXIS trial. Methods: 723 patients with clear-cell mRCC and progressive disease after 1 systemic therapy were enrolled, of whom 251 received prior interleukin-2 (IL-2) or interferon-α (IFN-α). Patients were randomized 1:1 to axitinib (5 mg twice daily [BID] starting dose) or sorafenib (400 mg BID). Results: As of Jun 3, 2011, mPFS (95% confidence interval [CI]) for cytokine-treated patients was 12.0 mo (10.1, 13.9) with axitinib (n=126) vs 6.6 mo (6.4, 8.3) with sorafenib (n=125): hazard ratio [HR] (95% CI) 0.519 (0.375, 0.720); p&lt;0.0001. For those treated with an IL-2-containing regimen, mPFS (95% CI) was 15.7 mo (8.3, 19.4) with axitinib (n=37) vs 8.3 mo (4.7, 15.7) with sorafenib (n=38). For those treated with IFN-α alone, mPFS (95% CI) was 12.0 mo (10.0, 13.8) with axitinib (n=89) vs 6.5 mo (6.4, 8.2) with sorafenib (n=87). As of Nov 1, 2011, median OS (95% CI) in the cytokine-treated subgroup was 29.4 mo (24.5, not estimable) with axitinib vs 27.8 mo (23.1, 34.5) with sorafenib: HR (95% CI) 0.813 (0.555, 1.191); p=0.144. Adverse event (AE) profiles were similar in both arms. Few cytokine-treated patients (5.6%) discontinued axitinib due to toxicity. AEs reported in &gt;25% of cytokine-treated patients receiving axitinib were diarrhea (49.2%), hypertension (47.6%), fatigue (35.7%), dysphonia (29.4%), and hand–foot syndrome (28.6%). Conclusions: Axitinib showed median PFS and OS of 1 and 2.5 yr, respectively, in cytokine-treated patients, confirming prior phase II study results, and was well tolerated. PFS was superior to that of sorafenib in second-line mRCC and compares favorably with historical results of other agents in second-line mRCC.