tbuckley/cabot-search huggingface dataset:
Abstract 13565: Early Discontinuation of Fondaparinux in Non-Invasive Treatment of Low-Risk Patients With Non-ST-Elevation Acute Coronary Syndrome is Associated With Reactivation of Coagulation Which is Apparently Clinically Unimportant
Authors: Igor S Yavelov, Anatoly S Knyazev, Anatoly B Dobrovolsky, Nikolai A Gratsiansky
Journal: Circulation (2014)

Background: Current guidelines recommend use of anticoagulants (preferably fondaparinux [F]) until hospital discharge in conservatively treated patients (pts) with non-ST-segment elevation acute coronary syndrome (NSTEACS). However, some evidence exists that anticoagulants may be safely stopped earlier in low-risk aspirin-treated patients. Aim: To assess feasibility of very early (after completion of risk assessment) discontinuation of F in non-invasive treatment of low-risk NSTEACS pts. Material and Methods: We included into prospective non-comparative study 53 pts admitted with NSTEACS at median 2.3 h after last episode of chest pain. All pts had GRACE score ≤108, negative Tn T (cut-off 0.03 ng/ml), and no ST-segment deviation >1 mV. Aspirin and beta-blockers were used in all cases while clopidogrel in 35 (66%). After single subcutaneous injection of F at presentation no anticoagulants were used. Plasma thrombin-antithrombin (TAT), D-dimer (DD) and plasmin-antiplasmin (PAP) levels were measured at media...
Oxidative stress as a signaling mechanism of the vascular response to injury The redox hypothesis of restenosis
Authors: L Azevedo
Journal: Cardiovascular Research (2000)

The prominent role of redox processes in tissue injury and in vascular cell signaling suggest their involvement in the repair reaction to vessel injury, which is a key determinant of restenosis post-angioplasty.Experimental studies showed a protective effect of superoxide dismutase or antioxidants on vasospasm, neointimal thickening or remodeling after balloon injury.It was also shown that oxidized thiols induce chelatable metal-dependent amplification of the vascular repair reaction.Ongoing or completed clinical trials show a promising effect of the antioxidant probucol against restenosis.However, few studies addressed the molecular physiological mechanisms underlying the redox hypothesis of restenosis.We recently showed evidence for marked oxidative stress early after balloon injury, with superoxide production mediated primarily by non-endothelial NAD(P)H oxidase-type flavoenzyme(s).This effect was closely related to the degree of injury.There is evidence supporting a role for such early redox processes in apoptotic cell loss and NF-kappa B activation.We present new data on the time course of oxidative stress after balloon injury of intact rabbit iliac arteries.Our data show that despite substantial neointimal growth and lumen narrowing, superoxide production and glutathione levels are unaltered at day 14 and 28 after balloon injury.At day 7 after injury, the peak neointimal proliferation in this model, there was significant decrease of vascular superoxide dismutase activity, without clear evidence of spontaneous superoxide production.Thus, oxidative stress after injury is likely to be an early transient event, which parallels the inflammatory and proliferative phases of the vascular response.We propose that such early redox processes act as dose-dependent signal transducers of gene programs that affect the final repair.
Frequency of zoledronic acid (ZOL) administration to prevent aromatase inhibitor-associated bone loss (AIBL)
Authors: A. Lipton, C. Campbell-Baird, Y. Chen, R. Dias, B. Kelly
Journal: Journal of Clinical Oncology (2009)

e11567 Background: Cancer patients (pts) are at increased risk of osteoporosis because of cancer treatment-induced bone loss. A hypogonadal state can increase bone resorption and turnover. Estrogen depletion with aromatase inhibitors (AIs), the preferred adjuvant treatment in postmenopausal women with early breast cancer (EBC), is associated with accelerated bone resorption and increased fracture risk. Several studies have demonstrated that IV ZOL can prevent AIBL in pts with EBC. ZOL to prevent AIBL was shown to be effective when administered every 6 mo in 4 large, randomized phase III trials. It is unknown if this is the optimal regimen. Methods: Pts who were receiving adjuvant breast cancer therapy with an AI and had a urinary N-telopeptide (uNTX) level &gt; 50 nmol/mmol creatinine (Cr) and a bone density T-score &lt; 1.5 at screening were treated with a single dose of ZOL 4 mg IV. Serum C-telopeptide (sCTX) and uNTX were obtained at baseline and then every 2 mo. Data are presently available from 10 pts who were followed for at least 6 mo and 1 pt followed for 2 mo after receiving ZOL. Wilcoxon signed-rank tests were performed for % change from baseline values. Results: Median baseline uNTX in these patients was 57.5 nmol/mmol Cr (range, 42.7 to 104.5). Median suppression of uNTX from baseline was 76.7% (range, 55.0% to 81.4%; P = .008) at 1 mo after therapy. At 6 mo, suppression of uNTX from baseline was 56.5% (range, 3.5% to 72.6%; P = .03). Similar significant suppression of sCTX up to 6 mo was observed. Continued suppression of uNTX and sCTX (approximately 50% decrease in median from baseline) was observed out to mo 12, although the number of pts studied is too small (n = 5 for uNTX and 4 for sCTX) to draw significant conclusions at this time. Pt accrual continues. Conclusions: A single dose of ZOL significantly suppressed bone resorption markers for at least 6 mo in pts receiving an adjuvant AI. It is not necessary to administer ZOL more frequently to prevent AIBL. These data suggest that ZOL administered every 6 mo is sufficient to prevent AIBL in this population. Further study will define whether this suppression of bone resorption markers continues for longer periods of time. [Table: see text]
The evaluation of peritoneal lavage tumor markers for gastric cancer
Authors: M. Yamamoto, T. Ishida
Journal: Journal of Clinical Oncology (2009)

e15643 Background: We have found that elevation of preoperative peritoneal lavage CEA levels is associated with an earlier detection of recurrent peritoneal dissemination and a poor prognosis. Methods: We have now examined findings with the combined of peritoneal lavage CEA, CA125 and CA72–4 levels with regard to prediction of the prognosis of gastric cancer patients. Ninety-four patients who were underwent surgery with gastric cancer were intraoperatively measured for tumor markers, CEA, CA125 and CA72–4 in peritoneal lavage using a chemiluminescent enzyme immunoassay. We examined whether the stage with patients were related with tumor markers in peritoneal lavage. Results: The averages of peritoneal lavage CEA, CA 125 and CA72–4 levels in patients with peritoneal carcinoma were 24.3, 299, 6.70, respectively, while those in patients without peritoneal carcinoma were 0.77, 258, 0.95, respectively. The averages of peritoneal lavage CEA and CA72–4 levels in patients with peritoneal carcinoma were significantly increased with those in patients without peritoneal carcinoma (p&lt;0.0001). In patients who were performed a curative surgery, the averages of peritoneal lavage CEA level were 0.55, 0.51, 0.51, 1.98, 0.50, 11.0 in cases of stage IA, IB, II, IIIA, IIIB and IV. Similarly, the averages of peritoneal lavage CA125 level were 254, 260, 307, 148, 366 and 280, and the average of peritoneal lavage CA72–4 level were 0.88, 1.06, 0.98, 0.90 and 3.23. The peritoneal lavage CEA or CA72–4 level in cases of stage IV was increased than in cases of other stages. The RFS of patients in the CEA level above cut-off was shorter than that in the CEA level below cut-off. However, the RFS of patients in the CA72–4 level above cut-off was not differ with that in the CA72–4 level below cut-off. In a multivariate analysis, the peritoneal lavage both CEA and CA72–4 levels above cut-off were found to be significant and independently prognostic factor (p= 0.0427). Conclusions: This combined assay of peritoneal lavage both CEA and CA72–4 levels will aid in estimating the prognosis. No significant financial relationships to disclose.
Clinical significance of <sup>18</sup>F-alpha-methyl tyrosine PET as a potential surrogate marker of LAT1 expression for predicting prognosis of non-small cell lung cancer.
Authors: N. Oriuchi, K. Kaira, K. Shimizu, H. Tominaga, H. Hanaoka, Y. Arisaka, T. Higuchi, T. Naoe, K. Endo
Journal: Journal of Clinical Oncology (2010)

10559 Background: Certain amino acids play critical roles in the signal pathway via mTOR which controls tumor progression. L-type amino acid transporter 1 (LAT1) is expressed in various types of cancer cells. [18F]-α-methyl tyrosine (18F-FAMT) is transported through LAT1, and is a candidate of tumor-specific radiotracer for PET. Previous studies have revealed that 18F-FAMT PET is useful to differentiate malignant tumors and the uptake is correlated with the LAT1 expression (Chest 2007; 131:1019, Clin Cancer Res 2007; 13: 6369). LAT1 expression is an independent prognostic factor of non-small cell lung cancer (NSCLC) (Lung Cancer 2009; 66: 120). The present study examined prognostic significance of 18F-FAMT PET in NSCLC. Methods: Eighty-eight patients with stage I to IV NSCLC underwent PET studies prior to therapy. They included 57 patients with adenocarcinoma (AC) and 31 with squamous cell carcinoma (SCC). Uptake of 18F-FAMT and 18F-FDG was evaluated by the maximal standardized uptake value (SUVmax). Overall survival (OS) was calculated by the Kaplan-Meier method and the prognostic significance was assessed. Results: SUVmax of 18F-FAMT in AC was significantly lower than that in SCC (p = 0.0031). The SUVmax of 18F-FDG showed no significant difference between AC and SCC. The best discriminative cutoff values of SUVmax for the 18F-FAMT and 18F-FDG in the primary tumors were 1.6 and 11, respectively. In the univariate analysis on all patients, high SUVmax was a significant factors to predict a poor OS in 18F-FAMT (p = 0.0129) and 18F-FDG PET (p = 0.0481). In AC patients, OS rates of patients with high SUVmax of 18F-FAMT (37.7%) was significantly lower than that with low SUVmax (81.5%, p = 0.0027). OS rates of patients with high SUVmax (31.7%) of 18F-FDG was also significantly lower than that with low SUV (65.8%, p = 0.0185). In patients with SCC, however, no significant difference in the OS was observed. Conclusions: 18F-FAMT PET is a potential prognostic marker in patients with pulmonary AC. No significant financial relationships to disclose.
Anchors Away
Authors: Carolyn S. Calfee, Sanjiv J. Shah, Paul J. Wolters, Sanjay Saint, Talmadge E. King
Journal: New England Journal of Medicine (2007)

A 50-year-old Asian woman presented with a papulonodular, erythematous rash on her legs below the knees. The skin lesions were nontender and nonpruritic and were accompanied by paresthesias. She had no fever, arthralgias, or other systemic symptoms.
Triple-negative breast cancer. A clinicopathologic study of 113 cases and comparison with 55 cases with triple positive breast cancer: A matched-control analysis
Authors: A. El Weshi, A. Tulbah, A. Al Sayed, T. El Twegeri, M. AL Shabanah, O. AL Malik, D. Ajarim
Journal: Journal of Clinical Oncology (2007)

21119 Background: Hormone receptor negative breast cancer (BC) is associated with poor outcome. BC patients (pts) with HER2/neu over expression (IHC 3+) are associated as well with poor prognosis. Aim: to further divide breast cancer to prognostic subgroups using interaction between these 2 prognostic factors. Methods: Between January 2002 and May 2004, the clincopathological features as well as treatment results of all non metastatic pts with triple negative BC (TNBC) and those with triple positive BC (TPBC) were reviewed. In all patients the three immunohistochemical markers, ER, PR and HER2/neu were available for review. Results: 113 TNBC pts and 55 TPBC were identified. In the TNBC group; median age was 42y, 76 % were premenopause, 21% with + family history (FH) and 6% were pregnant at diagnosis. Clinical stage (CS): I: 4%, II: 60%, III: 36%. Neo-adjuvant chemotherapy (NACT) was given to 29 %. Modified radical mastectomy (MRM) and breast conservative surgery (BCS) were performed in 49% and 51% respectively. Adjuvant CT (ACT) and radiotherapy (RT) were given to 85% and 84% of the pts. In the TPBC group, the median age was 43y, 71% were premenopause, 16% with + FH, and 2% were pregnant. The CS in the TPBC group was I: 4%, II: 65%, III: 31%. The distributions of NACT, MRM, BCS, ACT and RT in TPBC pts were 35%, 64%, 36%, 60% and 84% respectively. All TPBC pts received adjuvant hormonal therapy and non received adjuvant Herceptin. Relapse rate was 34% in TNBC and 20 % in TPBC (p = 0.04). At a median follow up of 40 months, 72% and 80% of the pts in the TNBC and TPBC groups are alive and disease free respectively. The 4y EFS and OS were 64% and 76% in TNBC and 74% and 89% in TPBC group (p = 0.04 and 0.008 respectively). Conclusions: TNBC is an aggressive neoplasm and has a poor outcome. More aggressive adjuvant chemotherapy and possible biological therapy directed against EGFR, based on previous released information of the prevalence of EGFR in this particular phenotype, should be considered in this group of patients. No significant financial relationships to disclose.
Adjuvant chemotherapy (AC) for muscle-invasive bladder cancer: A pooled analysis from phase III studies
Authors: E. M. Ruggeri, D. Giannarelli, E. Bria, P. Carlini, A. Felici, F. Nelli, F. Cognetti, C. F. Pollera
Journal: Journal of Clinical Oncology (2005)

4664 Background: Better treatment of muscle-invasive bladder cancer requires the eradication of local disease and the elimination of potential micrometastases. Yet, radical cystectomy remains the gold standard treatment for muscle invasive bladder cancer, since the role of peri-operative chemotherapy is still unclear. Although a meta-analysis (Vale, Lancet 2003) of neoadjuvant chemotherapy has shown a significant increase in overall survival (5% absolute benefit at 5-years), its clinical impact is limited because a number of patients is overtreated and the bladder is lost. AC has the advantage of being administered to patients with proper pathologic staging and known prognostic factors of relaspse risk. Few studies with limited samples and statistic power however have been published, thus providing insufficient evidence to support the routine use of post-cystectomy AC (Sylvester, Ann Oncol 2000). The aim of this pooled analysis is to verify if AC is able to increase the disease-free survival and then the overall survival of patients with muscle-invasive bladder cancer undergone to radical cystectomy. Methods: All published randomised phase III studies were considered eligible and a literature-based pooled-analysis was accomplished. The disease-free survival (DFS) and overall survival (OS) were the end-points. Event-based relative risk-ratio (RR) and 95% confidence intervals (CI) were derived. Combined effect estimation was computed with a fixed-effect model. An heterogeneity test (HT) was applied. Five trials were found for this analysis. All were evaluable for OS (350 patients) and 4 also for DFS (273 patients). Results: A significant benefit in favour of AC was seen both in 5-year OS (RR 0.75, 95% CI 0.62–0.90, p = 0.002) (HT p = 0.75), and in 3-year DFS (RR 0.62, CI 0.45–0.77, p < 0.0001) (HT p = 0.10). Conclusions: Although the results of this analysis are in favour of the use of AC, larger studies are clearly needed to define the role of AC in the treatment of muscle-invasive bladder cancer. Ongoing larger trials, such as the Italian study sponsored by National Research Council (NCI-V02–1715), incorporating new agents and combinations can help to better identify patients who can benefit from this approach. No significant financial relationships to disclose.
Poly (ADP-ribose) polymerase-1 (PARP1) inhibitor BSI-201 in combination with temozolomide (TMZ) in malignant glioma.
Authors: J. O. Blakeley, X. Ye, S. A. Grossman, T. Mikkelsen, M. R. Rosenfeld, C. R. Bradley, A. F. Eichler, L. B. Nabors, S. Desideri, J. G. Supko
Journal: Journal of Clinical Oncology (2010)

2012 Background: TMZ and radiotherapy (RT) improve survival in patients with glioblastoma multiforme. However, DNA repair mechanisms confer resistance to these therapies. Inhibition of PARP1, a critical DNA repair enzyme, enhances TMZ activity in glioma models. This study seeks to define the optimal dose of the PARP inhibitor BSI-201 given with TMZ in patients with newly diagnosed malignant glioma (MG). Methods: Eligibility: newly diagnosed MG; ≥18 yrs; received ≥80% of planned RT and concurrent TMZ without grade 3/4 toxicity. Patients received either TMZ 75 mg/m2 qd with BSI-201 biweekly for 6 wks or TMZ 150-200 mg/m2 days 1-5 every month with BSI-201 biweekly. The dose of BSI-201 was determined using the continual reassessment model with cohorts of 5 patients. Pharmacokinetic and pharmacodynamic (PD) samples were collected pre- and postinfusion (cycles 1, 2, 3 and off treatment). Results: 30 patients have been accrued. See Table for grade 3/4 adverse events. Maximum plasma concentration (Cmax) of BSI-201 and its two metabolites did not differ between infusions 1 and 2 in cycle 1 or across cycles 1 and 2 for patients in the same dose level, nor was it affected by TMZ dose or schedule. Mean BSI-201 Cmax increased with dose escalation from 518±93 ng/mL (n = 8) at 5.1 mg/kg, 692±180 ng/mL (n = 5) at 6.1 mg/kg, to 1006±96 ng/mL (n = 5) at 6.8 mg/kg. Plasma levels of BSI- 201 were 47- and 104-fold higher than each metabolite. PD samples are in process. Conclusions: Peak plasma levels at the end-of-infusion were higher than those associated with efficacy in preclinical models. BSI-201 was well tolerated with conventionally prescribed doses of TMZ given during and following RT in newly diagnosed MG. An MTD of BSI-201 with TMZ has not been reached. This is an encouraging safety profile for the first PARP inhibitor to be given with TMZ in patients with MG. Additional studies are needed to ensure that adequate concentrations of BSI-201 and PARP inhibition are achieved in MG tissue. Dosing cohorts n Grade 3 Grade 4 BSI-201 with TMZ 75mg/m2 daily x 42 days 5.1 mg/kg 5 0 2a 6.1 mg/kg 5 2b 0 6.8 mg/kg 5 0 0 BSI-201 with TMZ 150-200 mg/m2 for 5/28 days 5.1 mg/kg 5 2c 0 6.8 mg/kg 5 1d 0 8.6 mg/kg 5 0 0 a Thrombosis. b Lymphopenia. c Uticaria/platelets. d Elevated LFT. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration BiPar Sciences BioPar Pharma BioPar Pharma
Evaluation of factors associated with recruitment in hematological clinical trials: A retrospective study
Authors: C. Amireault, S. Camden, J. Poulin, J. Lemieux
Journal: Journal of Clinical Oncology (2009)

6567 Background: Recruitment of patients in cancer clinical trials has been reported to be between 3%–5%. Very few data come from Canada. Methods: The objective was to measure the recruitment and its associated characteristics in hematology clinical trials for malignant diseases. This was a retrospective cohort study using charts review in a tertiary hematology centre in Québec City, Canada. Clinical trials opened between 2002 and 2008 were selected. For each protocol, main criteria were used to define the population under study (e.g., stage IV Hodgkin lymphomas first-line). If the patient filled the main criteria, all eligibility criteria (inclusion and exclusion criteria) of the protocol were assessed. Results: Among all charts reviewed, 697 patients were identified in 17 protocols. However, as a patient could be assessed for more than one protocol if applicable, this population reached 1,394 observations. The study population filling the main criteria of a protocol included 195 observations in 17 protocols (186 different patients). Only 9.7% (8.2–11.4) filled all the eligibility criteria and 3.3% (2.5–4.4) were recruited among all charts reviewed (1394 observations). However, theses rates reached 68.2 % (61.2–75.1) and 23.1 % (17.9–29.8), respectively, among patients meeting the main criteria of a protocol (195 observations). Recruitment in the population who filled all eligibility criteria (inclusion and exclusion criteria) was 33.8% (26.7–42.5). Patient's sex, age, comorbidities, doctor's sex, doctor's age and protocol characteristics were not associated with recruitment in the population filling the main criteria, but having a note in the chart about the protocol appears to be associated with higher recruitment (p &lt; 0.0001). The most common reasons for not being recruited were as follow (could have more than one reason): 40.7% not fulfilling all eligibility criteria, 31.3% protocol not being proposed and 22.7% patients’ refusal. Patients reasons for refusals were (could have more than one reason): 50% unknown, 26.5% fear of side effects, 20.6% too many visits, 14.7 % already enough anxious about disease, other. Conclusions: The largest barriers about recruitment were protocol ineligibility and protocol not being proposed by the medical team. No significant financial relationships to disclose.
Bortezomib Plus Dexamethasone (VD)Versus Reduced-dose bortezomib Plus Thalidomide Plus Dexametasone (vTD) as Induction Treatment Prior to Autologous Stem-Cell Transplantation (ASCT) in Newly Diagnosed Multiple Myeloma (MM).
Authors: Jean-Luc Harousseau, Hervé Avet-Loiseau, Thierry Facon, Michel Attal, Chantal Doyen, Cyrille Hulin, Laurent Garderet, Mourad Tiab, Gerard Lepeu, Christine Aranjo, Denis Cailliot, marie-Odile Petillon, Claire Mathiot, Jean Yves Mary, Philippe Moreau
Journal: Blood (2009)
GemOx (Gemcitabine + Oxaliplatin) versus Gem (Gemcitabine) in non resectable pancreatic adenocarcinoma : final results of the GERCOR /GISCAD Intergroup Phase III
Authors: C. Louvet, R. Labianca, P. Hammel, G. Lledo, F. de Braud, T. Andre, M. Cantore, M. Ducreux, A. Zaniboni, A. de Gramont
Journal: Journal of Clinical Oncology (2004)

4008 Background: The combination of gemcitabine 1 g/m2 as a 100 min infusion (10 mg/m2/mn) D1 and oxaliplatin 100 mg/m2 in 2h infusion D2 (GemOx) every two weeks showed interesting results in a multicenter phase II study (Louvet et al, JCO 2002) and was thus further explored in a phase III randomised study. Methods: Patients were stratified according to center, performance status and type of disease (locally-advanced (LA) versus metastatic (M)) and were randomly assigned to GemOx or standard treatment with gemcitabine alone (1 g/m2 in a 30 min infusion weekly). 300 patients were needed to demonstrate an absolute improvement of 20% in 8-month survival (30% to 50%). Results: 326 patients have been enrolled; 13 were non eligible, 156 were allocated to Gem arm and 157 to GemOx. Preliminary results presented last year (Louvet, ASCO 2003) were actualized and confirm a significant improvement for the GemOx arm in response rate (28.7% vs 16.7%, p = 0.02), median progression free survival (5.5 months vs 3.7, p = 0.04), and clinical benefit (38.9% vs 29.2%, p = 0.05), with a good tolerability of the GemOx combination. Final analysis (March 04) has shown median overall survival of 7.1 months (Gem) and of 9.0 months (Gemox), respectively (p = 0.13, HR 1.20 [.95 - 1.54]). The 8-month survival probability was 45% in the Gem arm and 56% in the Gemox arm. For LA pts (30% of total enrolled), median survivals were identical (10.3 months) in both arm, while for M pts (70%), median survival was 6.7 months (Gem) arm and 8.5 months (Gemox), respectively (p = 0.17; HR 1.21 [.91 - 1.63]. A second-line chemotherapy was administered in 53.4% of the Gem pts (mainly platin-based) and in 52.3% of the Gemox pts (miscellaneous). Conclusion: Gemox achieved significantly better results than Gem in terms of RR, clinical benefit and PFS, but the difference did not reach the significant level for OS. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo Sanofi-Synthelabo