tbuckley/cabot-search huggingface dataset:
Treatment profiles in patients with cancer aged 80 years or more
Authors: A. M. Noonan, A. M. Horgan, L. Grogan, O. S. Breathnach
Journal: Journal of Clinical Oncology (2007)

19620 Background: There is much criticism about the omission of very elderly patients (&gt;80 years old) from clinical trials. The question is raised as to whether results of clinical trials performed with younger pts (usually &lt;75 years) can be extrapolated to the very elderly population. The most recent Irish census predicts that those aged =80 yrs is set to rise dramatically from the 2001 level of 98,000 to a projected 323,000 in 2036. Accordingly oncologists will have to plan carefully to appropriately treat these pts. Methods: A retrospective review of all new pts referrals aged =80 years was performed for the period Sept. 2005 to Sept. 2006. Pts records were analysed for age, cancer diagnosis, co-morbidities, treatment plan and complications. Results: A total of 52 referrals were identified but records were available for only 49 pts. The average age was 83.7 years (80–93yrs). The M:F ratio was 1.04:1. The 4 most common cancers were Colorectal (20%), lung (18%), oesophageal (12%) and breast (10%). The mean number of co-morbidities was 5. 13 pts (26%) had a previous unrelated cancer diagnosis. 19 patients (38.8%) received cancer treatment (see table ). Three other pts were offered chemotherapy but declined citing age and fear of side effects as their reasons. 68% of patients receiving cancer treatment had a performance status (PS) of ECOG =1. The main reasons cited for not giving cancer treatment were poor PS (21), comorbidities (13), or patient preference (3). 75% of patients receiving chemotherapy were on schedule with no delays. Only 25% (2) of patients experienced delays due to toxicity. Conclusion: In this diverse group of very elderly cancer pts, those that received cancer treatment tolerated it reasonably well. However, 55% of pts were deemed unfit for cancer treatment at presentation due to poor performance status or compromising co-morbidities. This fact must be taken into account when setting recruitment targets for this age group when planning oncology clinical trials. No significant financial relationships to disclose. [Table: see text]
Dynamic contrast-enhanced MRI for assessing the disease activity of multiple myeloma: A comparative study with histology, proangiogenic cytokines and clinical markers
Authors: J. Hillengass, S. Nosas-Garcia, K. Wasser, F. Kiessling, R. Bartl, I. Zuna, S. Delorme, A. D. Ho, H. Goldschmidt, T. Moehler
Journal: Journal of Clinical Oncology (2004)

6719 Background: Dynamic contrast-enhanced MRI (dMRI) of the bone marrow has been used for assessing treatment response in multiple myeloma (MM). Aim of this study was to examine whether parameters of dMRI reflect the degree of infiltration and vessel density in corresponding bone marrow biopsy specimens. Furthermore levels of proangiogenic cytokines in peripheral blood and bone marrow were compared with findings of dMRI. Methods: The pelvis of 24 patients with MM was examined using Gd-DTPA-enhanced dMRI. Biopsy was obtained from the spina iliaca posterior superior. Using a two-compartment model, the parameters amplitude A and exchange rate constant k21 in the biopsied region were calculated and compared with the histological and clinical data. The proangiogenic cytokines Hepatocyte Growth Factor (HGF), Vascular Endothelial Growth Factor (VEGF) and Basic Fibroblast Growth Factor (bFGF) were measured in peripheral blood and bone marrow of 36 patients. The results were correlated with dMRI parameters. Results: DMRI parameters were significantly higher in lesions with marked infiltration than with mild or no infiltration (p<0.05). Amplitude A, but not exchange rate constant k21 was higher in lesions with high vessel-density at histology (p=0.01). Higher levels of the exchange rate consant k21 were found in presence of increased serum immunoglobulins. We detected a significant positive correlation of HGF concentration in peripheral blood with amplitude A of the lumbar spine (p = 0,05). Conclusions: Increased contrast uptake in the bone marrow of MM patients indicates at least moderate tumor involvement. The contrast enhancement correlates with the degree of plasma cell infiltration and vessel-density. The correlation between HGF and bone marrow microcirculation as detected by dMRI supports the role of HGF in regulation of bone marrow microcirculation and angiogenesis in MM. No significant financial relationships to disclose.
Impact of the ATAC trial on prescribing of hormonal therapy in breast cancer
Authors: R. M. Connolly, T. I. Barron, K. Bennett, J. Feely, M. J. Kennedy
Journal: Journal of Clinical Oncology (2007)

11028 Background: The arimidex, tamoxifen, alone or in combination (ATAC) trial recommended use of anastrazole over tamoxifen as initial adjuvant hormonal therapy of early breast cancer in postmenopausal women. The aim of this study was to investigate the impact of the publication of the ATAC trial in December 2004 on subsequent prescribing of hormonal therapy to Irish women =55 years old. Methods: The Irish HSE-PCRS pharmacy claims database was used to identify all women =55 years old, commenced on tamoxifen or an aromatase inhibitor as initial hormonal therapy, between July 2000 and June 2006. A segmented regression analysis of an interrupted time series was used to detect changes in the trend and level of anastrazole prescribing after publication of the ATAC trial in December 2004 and the prior updates in November 2003 and June 2002 (presented December 2001). β coefficients and 95%CI are presented where appropriate. The absolute change in anastrazole prescribing and 95%CI are also calculated for selected months. Statistical analysis was performed using SAS version 9.1. Significance at p&lt;0.05 is assumed. Results: A cohort of 7,604 women =55 years old, commenced on initial hormonal therapy, was identified from the HSE-PCRS database, 2,206 (29%) of these women were prescribed anastrazole. In the month following publication of the final results of the ATAC trial there was a 17.6% (95% CI 10.8%, 24.5%) absolute increase in anastrazole prescribing. This represented a statistically significant increase in the level of prescribing (level change β=18.1 95% CI 11.3, 24.9 p&lt;0.0001). There was also a significant change in anastrazole prescribing trend after presentation of the first ATAC update (slope change β=0.98 95% CI 0.59, 1.37 p&lt;0.0001). Conclusion: The publication of the final ATAC trial data resulted in a significant increase in the prescribing of anastrazole. This is objective evidence that oncologists respond rapidly to clinical trial results. It is unclear whether the significant increase in anastrazole prescribing after the first ATAC update is an appropriate response to an interim analysis. No significant financial relationships to disclose.
Abstract 13288: Baseline Radial Dyssynchrony by Speckle Tracking Echocardiography is Associated with Favorable Clinical Outcomes after Cardiac Resynchronization Therapy: Analysis from the MADIT-CRT Trial
Authors: John Gorcsan, Wojciech Zareba, Anne Catherine Pouleur, Dorit Knappe, Valentina Kutyifa, J Moss, Scott D Solomon
Journal: Circulation (2012)

Background: The importance of echocardiographic dyssynchrony as a predictor of response to cardiac resynchronization therapy (CRT) has been unclear. Objective: To test the hypothesis that patients ...
SOFIA: Phase II study of neoadjuvant epirubicin, cyclophosphamide (EC) plus sorafenib (S) followed by paclitaxel (Pw) plus sorafenib (S) in women with previously untreated primary breast cancer (BC).
Authors: S. Loibl
Journal: Journal of Clinical Oncology (2010)

TPS112 Background: Sorafenib is an oral RAF/RAS kinase inhibitor with antiangiogenetic potential. In metastatic BC it shows modest single agent activity but prolongs survival in combination with capecitabine. EC-P is a standard neoadjuvant chemotherapy regimen suitable to be combined with new drugs. The aim is to increase pCR by combining EC with S. Sorafenib might affect the pharmacokinetic (PK) of anthracyclines, therefore a pharmacokinetic study was implemented into this trial. Methods: SOFIA is an open-label, multicentre, single-arm, phase II study. Inclusion criteria are: uni- or bilateral, HER2-negative, cT3, cT4 or cT2 cN+, M0 primary BC. Pts receive 4x E 90 mg/m2 and C 600 mg/m2 i.v. q3w followed by 12 weeks Pw 80 mg/m2 q1w. The study started with S 400 mg bid given concomitantly with the chemotherapy with a 3-day drug holiday around EC. PK samples are taken during the first 2 EC cycles. Primary objective is the pCR rate at time of surgery; main secondary objectives are the assessment of safety, DFS, OS and clinical response. An exact binomial test with an alpha of 10% will have an 80% power to detect the difference between the null hypothesis proportion, pCR of 25% and the alternative proportion, pCR of 40% when the sample size is 62 patients. Because of an unexpected high number of early withdrawals due to skin toxicity (any grade) the study has been amended in 9/2008. The S dose starts with 200mg in the 1st EC cycle and will be escalated up to 800mg at every EC cycle depending on pts individual skin toxicity. So far, 24 patients have been recruited and the first safety analysis for the two patient cohorts has been undertaken to decide which strategy should be carried forward. No significant financial relationships to disclose.
A joint United Kingdom (UK) and Hong Kong (HK) study to determine prognostic factors for hepatocellular carcinoma (HCC) undergoing curative and palliative treatment.
Authors: Stephen Lam Chan, Philip James Johnson, Frankie Mo, Sarah Berhane, Brigette Ma, Mabel Teng, Darren M. C. Poon, Janet Morse, Anthony T. C. Chan, Winnie Yeo
Journal: Journal of Clinical Oncology (2014)

181 Background: There have been few international studies that systematically evaluate the impact of geographical region on the prognosis of HCC. Methods: Prospective cohorts of patients (pt) were accrued in UK (n=567; 2006-2011) and HK (n=517; 2007-2012). Clinical data were documented at baseline; treatments were decided by multidisciplinary teams at both centers. Results: The median follow-up time of the UK and HK cohort was 27.9 and 29.8 months, respectively. The median overall survival (OS) of the whole UK and HK cohort was 22.9 months and 8.6 months. In the HK cohort, 425 underwent palliative treatment (TACE, systemic agents or supportive care) and 92 had curative treatment (surgery and locoablation); in the UK cohort, 338 had palliative treatment and 228 underwent curative treatment. In the curative group, the median OS was 54.8 months in the UK cohort but has not yet been achieved in the HK cohort. For the palliative group, the median OS was 12.7 and 5.5 months in the UK and HK cohort respectively. In the palliative group, geographical difference was an independent prognostic factor (HK vs. UK, HR=2.0; p&lt;0.0001). Other prognostic factors were mainly tumorous features and Child’s liver function (Table). In the curative group, neither geographical difference nor Child’s score were prognostic factors. Conclusions: Separate prognostic factors exist for curative and palliative treatment. Geographical differences need to be considered during design of clinical trials on novel agents where palliative treatments are investigated but not for surgery or locoablation. [Table: see text]
A Phase I Study of the Anti-Activin Receptor-Like Kinase 1 (ALK-1) Monoclonal Antibody PF-03446962 in Patients with Advanced Solid Tumors
Authors: Laura W. Goff, Roger B. Cohen, Jordan D. Berlin, Filippo G. de Braud, Andrej Lyshchik, Cristina Noberasco, Francesco Bertolini, Marina Carpentieri, Corrado Gallo Stampino, Antonello Abbattista, Erjan Wang, Hossein Borghaei
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Objectives of this dose-finding study were to determine the MTD and recommended phase II dose (RP2D) of the first-in-class anti-activin receptor-like kinase 1 (ALK-1) monoclonal antibody PF-03446962, and assess safety and antitumor activity in patients with advanced solid tumors. Experimental Design: This open-label, multicenter study was based on a 3+3 design. PF-03446962 was administered biweekly by intravenous infusion, at doses ranging from 0.5 to 15 mg/kg. Results: Forty-four patients received treatment with PF-03446962. Dose-limiting toxicities observed during dose escalation included grade 3 increased amylase, grade 3/4 increased lipase, and grade 3/4 thrombocytopenia. The MTD was determined to be 10 mg/kg. The RP2D was set at 7 mg/kg for patients with advanced solid tumors, based on the observed safety, pharmacokinetics, and antitumor activity. The most-frequent treatment-related, all-grade adverse events included thrombocytopenia (20.5%), fatigue (15.9%), and nausea, increased amylase, and increased lipase (each 11.4%). Treatment-related telangiectasia was noted in 7% of patients, suggesting in vivo inhibition of the ALK-1 pathway. None of the deaths was deemed to be treatment-related. Three (6.8%) patients with advanced hepatocellular carcinoma, renal cell carcinoma, or non–small cell lung cancer achieved a partial response, and 12 (27.3%) patients had stable disease, across dose levels. Contrast-enhanced ultrasound analysis of tumor vascularity showed reduction in tumor perfusion in 2 patients with stable disease following treatment with PF-03446962. Conclusions: The clinical activity demonstrated in this study points to PF-03446962 as a novel approach to antiangiogenic therapy, with manageable safety profile and single-agent, antitumor activity in patients with advanced solid tumors. Clin Cancer Res; 22(9); 2146–54. ©2015 AACR.
Phase I trial of vendetanib and oral etoposide for recurrent malignant gliomas
Authors: J. Herndon, J. Vredenburgh, D. Reardon, A. Desjardins, K. Peters, S. Gururangan, J. Norfleet, A. Friedman, D. Bigner, H. S. Friedman
Journal: Journal of Clinical Oncology (2009)

e13016 Background: Recurrent malignant gliomas have a poor prognosis, with a median survival of 6–15 months, with grade 4 glioblastomas more aggressive than grade 3 anaplastic astrocytomas or oligodendrogliomas. Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) are critically important in glioma biology. Vandetanib is a multi-kinase inhibitor, predominantly of VEGF and EGF. We report a phase I trial of vandetanib in combination with oral etoposide for recurrent malignant glioma. Methods: Patients with histologically documented recurrent grade 3 or grade 4 malignant glioma were eligible. Patients were treated with daily oral vandetanib and oral etoposide. The trial design was a modified 3 + 3 Phase I design, with the dose levels outlined below. Results: Eighteen patients have been accrued. There was more hematologic toxicity than expected, with 3/6 of the patients enrolled at dose level 1 developing grade 4 neutropenia. There were no DLT's at the -1 dose level. The protocol was amended to decrease the dose of etoposide to 50 mg daily for 21 days, then 7 days off and dose escalation of vandetanib started again at 100 mg daily. Six patients had no dose limiting toxicity at the new dose level 1 of vandetanib 100 mg daily and etoposide 50 mg daily. Dose escalation continues. There has been clinical activity, with patients remaining stable on study for multiple cycles. Conclusions: Vandetanib and oral etoposide appear to interact to produce more marrow toxicity than expected. A phase II trial is planned when the MTD of vandetanib with reduced dose etoposide is determined. [Table: see text] No significant financial relationships to disclose.
Predictors of long-term survival in lung cancer patients (p) included in the randomized Spanish Lung Cancer Group 0008 phase II trial using concomitant chemoradiation with docetaxel (D) and carboplatin (Cb) plus induction (I) or consolidation (C) chemotherapy (CT) with docetaxel and gemcitabine (G)
Authors: P. Garrido Lopez, R. Rosell, B. Massutí, F. Cardenal, V. Alberola Candel, M. Dómine, R. García Gómez, I. Maestu, D. Isla, M. López-Brea
Journal: Journal of Clinical Oncology (2008)

7574 Background: There is little information about prognostic variables associated with long term survival in stage III NSCLC p treated with concomitant chemoradiotherapy. Methods: Unresectable stage III p with IK ≥ 70, forced expiratory volume in 1 second (FEV1) of ≥ 1L and weight loss < 5% were initially randomized to sequential treatment (arm A), concurrent CT/TRT followed by consolidation CT (arm B) or induction CT followed by CT/TRT (arm C). Based on RTOG 9410 results, arm A was closed and the study continues with two concomitant arms (B, C). All p receive 2 cycles of D 40 mg/m2 d1, 8 plus G 1,200 mg/m2 d1, 8 as I or C therapy. Concomitant treatment includes D 20 mg/m2 and Cb AUC 2 weekly plus 60 Gy TRT. In order to identify factors that affected survival duration an univariate analysis and a Cox proportional hazards regression were performed including the following variables: age (< 70 or > 70), sex, ECOG (0 vs 1), FEV1 (>2 L vs 1–2 L), stage III (A vs B), N disease (N0 vs N1–2 vs N3), Hb level (≥12 gr/dl vs < 12 gr/dl), RT treatment completed (yes vs no), I or C plus concomitant treatment completed (yes vs no) and prolonged RT delay (≥ 7 days vs > 7 d). Results: From May 01 to Jun 06, 151 p were included (A: 19, B: 66, C: 66). Efficacy and survival data were already presented. With a median follow-up of 23 months (m), no statistically significant differences in terms of MST (13.7 m [B] and 14.6 m [C]) or 4-years survival (27% [B] and 34% [C]) were found. In the Cox regression analysis only RT treatment completed (p < 0.0001) and I or C plus concomitant treatment completed (p < 0.0001) were associated with improved survival. Conclusions: Based in this retrospective analysis neither age, sex, ECOG nor clinical parameters are good predictors for OS in p candidate to concomitant treatment whereas finishing the treatment is needed for achieve long term results. No significant financial relationships to disclose.
Intrinsic Resistance To the Antiproliferative Effects of Azd6244 a Selective Mek1/2 Inhibitor Is Associated With Concomitant K-ras and Pi3kca Gene Mutations in Colorectal Cancer Cells
Authors: T. Troiani, I. Vecchione, A. Capasso, E. Martinelli, M. Caraglia, M. Marra, Wendy De Roock, Sabine Tejpar, E. Van Cutsem, F. Ciardiello
Journal: Annals of Oncology (2010)
Establishment of human primary non-small cell lung cancer xenograft models for test of cytotoxic and targeted anticancer drugs
Authors: C. Liu, Y. Liu, D. Chen, Z. Tang, W. Pan, J. Wery, Y. Chen
Journal: Journal of Clinical Oncology (2009)

11008 Background: New oncology drug development has moved from general cytotoxic agents to molecular target-directed therapeutics. Consequently, there is a need to identify tumor types and individual patient tumors that express the target and could benefit from more selective therapies in clinical trials. Therefore, the in vivo models used in preclinical development should be“disease-oriented” and target-directed. Recently, we developed non-small cell lung cancer (NSCLC) xenograft models by transplanting human fresh tumor fragments into nude mice, which have been used for test of cytotoxic and targeted anticancer drugs. Methods: The fresh NSCLC tumors were collected from local hospitals. The tumor fragments were subcutaneously implanted into nude mice. The EGFR and K-ras mutation status of the tumors were investigated and compared with the efficacy results. The test drugs included paclitaxel, gemcitabine, and the epidermal growth factor receptor (EGFR) inhibitor erlotinib. Results: A total of 72 NSCLC samples were implanted, and 13 tumor models were established (tumor taking rate 18%) for the first passage. The tumor taking rates were higher in the second and third passages (80–100%). Paclitaxel and gemcitatbine produced tumor growth inhibition rates of 50–53% regardless of the EGFR and K-ras mutation status. While erlotinib demonstrated a significant antitumor activity only in the tumors bearing EGFR mutation with wild-type K-ras, which were consistent with their clinical findings. The tumor xenografts’ architecture, the cell and histopathological morphology from the three generations mirrored the original patient cancers. Conclusions: These results suggest that human primary tumor xenograft models provide a unique renewable source of tumor material for test of novel anticancer agents. They may predict more relevant clinical response rates and higher correlation with clinical findings than use of xenograft models established from long-term cultured cancer cell lines, especially for test of target-oriented therapeutics in new drugs development programs. No significant financial relationships to disclose.
Course of Henoch-Schönlein purpura after renal transplantation: a multicenter analysis
Authors: Nada Kanaan, Georges Mourad, Eric Thervet, Patrick Peeters, Maryvonne Hourmant, Yves Vanrenterghem, Martine De Meyer, Jef Struyven, Eric Goffin, Yves Pirson
Journal: Journal of the American Society of Nephrology (2008)
Results from a phase I clinical trial with IGN311, a fully humanized IgG1 antibody against Lewis Y in patients with solid tumors expressing Lewis Y antigen
Authors: D. V. Oruzio, C. Aulmann, N. Eller, G. Mudde, O. Obwaller, G. Waxenecker, O. Scheiber, S. Stranner, G. Schlimok
Journal: Journal of Clinical Oncology (2004)

2624 Background: IGN311 is a humanized monoclonal antibody (mab) binding to Lewis Y, a blood group-related carbohydrate determinant that has been found to be associated with 60–90% of human epithelial carcinomas (ca) incl. breast, colon, gastric and lung cancers. IGN311 is a fully humanized IgG1 variant 1 of the parent murine IgG3 mab ABL 364. Methods: Open-label, single treatment arm, uncontrolled dose escalating phase I study, enrolling 10 evaluable subjects. 7 Patients had colorectal cancer, 1 gastric cancer, 1 pancreatic cancer, 1 breast cancer. Pts: >18y, biopsy-proven ca that has failed or is considered refractory to standard agents, KPS >70 at baseline, an estimated life expectancy >4 months. No chemotherapy for at least 4 weeks prior to start of trial. Treatment: 50 or 100 or 200 mg IGN311 given by iv infusion on day (d) 1 and 15; final visit on d43. Primary Objective: Safety, tolerability, immunogenicity (human anti human antibodies, HAMA). Secondary Objectives: serum half-life, ex-vivo CDC activity, detection of tumor cells in peripeheral blood (pb) before and after IGN3111. Results: 10 pts of the cohorts 1,2 and 3 completed the study. 3 pts received 50mg, 3 pts 100mg, 4 pts 200mg IGN311. 5 adverse events (ae) were observed. The toxicity grading was in the range 1–3. In the 200mg cohort, the only two most probably drug related grade III ae were documented (vomiting, skin reaction) in one pt. A total of 4 serious ae (sae) events occurred so far. These sae were tumor related. Two pts with sae died within day 43 most probably due to tumor progression. The t1/2 of IGN311 is up to ∼20 days. At a dose of 100 mg, cdc remains above background at all time points of the study. One type I-HAHA response occured without side effects. HAHA response declined with a t1/2 of 21 days. Numbers of tumor cells in pb were reduced substantially after two infusions of IGN311 in 2/7 pts. Conclusions: IGN311 confirmed a good safety profile, preclin. pharmakokinetic and -dynamic data and indicates effects against pb tumor cells. Further clinical trials are in preparation to substantiate the clinical profile of IGN311. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Igeneon Igeneon