tbuckley/cabot-search huggingface dataset:
A phase II trial of capecitabine and docetaxel in patients with previously treated pancreatic cancer
Authors: G. Lopes, B. Bastos, E. Ahn, J. A. Quesada, M. Allison, A. Flores, A. Ribeiro, J. Levi, J. Macintyre, C. M. Rocha-Lima
Journal: Journal of Clinical Oncology (2006)

14111 Background: There is no accepted standard treatment for patients with advanced pancreatic cancer who progress after gemcitabine-based therapy. Capecitabine and docetaxel have single-agent activity in pancreatic cancer and have documented synergy in both pre-clinical models and in the treatment of other solid tumors. Methods: A phase II trial with a 3-stage sequential design was planned to assess the efficacy (primary end-point: response rate) and toxicity of capecitabine 800 mg/m 2 PO bid on days 1–14 in combination with docetaxel 30 mg/m 2 IV on days 1 and 8 of each 21-day cycle in patients with advanced pancreatic cancer who failed first-line gemcitabine-based chemotherapy. If no responses are observed after 13 patients or less than 3 responses are seen after 26 patients, accrual will stop and the combination deemed ineffective. Results: Eight patients have been enrolled (5 women, 3 men). Median age was 67 years. ECOG PS was as follows: PS 1, three patients; PS 2, five patients. All patients had adequate organ function. A total of 26 cycles have been administered (median: 2 cycles, range 1 to 8). Four patients had stable disease (median duration 9 weeks, range 6 to 24), and 3 had progressed at the time of first evaluation (2 cycles). One patient has not yet completed 2 cycles and is therefore not assessable for radiologic response. Out of 7 patients with an elevated CA 19–9, four had a decrease of 50% or greater while on chemotherapy. Grade 1 or 2 toxicity was seen in 3 patients (diarrhea, 1 patient; fatigue, 2 patients). Grade 3 or 4 toxicity was as follows: fatigue, 2 patients; dehydration, 1 patient; neuropathy, 1 patient. There were no treatment related deaths. Enrollment continues. Efficacy data fulfilling the first stage sequential design should be available at the time of the meeting. Median survival for all patients is currently 13 weeks (range 7–23 weeks) Conclusions: Capecitabine in combination with docetaxel is a well-tolerated regimen in the treatment of patients with pancreatic cancer who have failed prior gemcitabine-based therapy. Four out of 8 patients have had stable disease. Four of 7 patients have had a decrease of 50% or greater in CA 19.9 levels. Enrollment continues. Median survival of 13 weeks underscores the poor prognosis of this patient population. [Table: see text]
Vandetanib plus mFOLFOX6 in patients with advanced colorectal cancer (CRC): A randomized, double-blind, placebo-controlled phase II study
Authors: T. S. Yang, D. Y. Oh, R. Guimbaud, J. Szanto, T. Salek, L. Thurzo, J. M. Vieitez, G. M. Pover, T. W. Kim
Journal: Journal of Clinical Oncology (2009)

4084 Background: Vandetanib is a once-daily oral agent that selectively targets key signaling pathways in cancer by inhibiting VEGF, EGF and RET receptor tyrosine kinases. Methods: Eligible patients with advanced CRC and who had previously progressed after an irinotecan- and fluoropyrimidine-containing regimen were randomized 1:1:1 to receive once-daily oral vandetanib (100 or 300 mg) + modified FOLFOX6 (mFOLFOX6) or placebo + mFOLFOX6; mFOLFOX6 was given as standard 14-day treatment cycles (oxaliplatin 85 mg/m 2 2-hr and leucovorin 400 mg/m 2 2-hr i.v. infusions, followed by 5- fluorouracil [5-FU] 400 mg/mg 2 i.v. bolus and 5-FU 2400 mg/m 2 46-hr i.v. infusion). The primary objective was to compare the number of patients with a progression event on or before a mandatory tumor assessment visit at data cut-off (∼4 months after last patient randomized). A progression event was defined as the earliest of objective and/or clinical disease progression, or death from any cause. Results: Between March and November 2007, 104 patients (aged 32–81 years) were randomized to receive study treatment ( Table ). At data cut-off on 8 March 2008, there was a greater % of progression events in the vandetanib 100 mg arm compared with placebo (72% [n=23] versus 65% [n=24]; HR=1.21, 2-sided 80% CI 0.82–1.80; 2-sided P=0.53), and also in the vandetanib 300 mg arm compared with placebo (77% [n=27] versus 65% [n=24]; HR=1.41, 2-sided 80% CI 0.96–2.07; 2-sided P=0.25). All except one patient in each group experienced an adverse event (AE) during the study with diarrhea, nausea, thrombocytopenia, and peripheral sensory neuropathy the most commonly reported AEs ( Table ). Neutropenia was the only CTC grade 4 AE to occur in &gt;1 patient in any group (n=2, vandetanib 100 mg arm; n=0, vandetanib 300 mg arm; n=3, placebo arm). Conclusions: In this study of patients with advanced, previously treated CRC, there was no efficacy benefit for vandetanib (100 or 300 mg) + mFOLFOX6 versus placebo + mFOLFOX6. [Table: see text] [Table: see text]
Bevacizumab, irinotecan, and radiotherapy versus standard temozolomide and radiotherapy in newly diagnosed, MGMT-non-methylated glioblastoma patients: First results from the randomized multicenter GLARIUS trial.
Authors: Ulrich Herrlinger, Niklas Schaefer, Joachim Peter Steinbach, Astrid Weyerbrock, Peter Hau, Roland Goldbrunner, Franziska Friedrich, Florian Stockhammer, Florian Ringel, Christian Braun, Ralf Kohnen, Barbara Leutgeb, Claus Belka, Horst Urbach, Walter Stummer, Martin Glas
Journal: Journal of Clinical Oncology (2013)

LBA2000 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday, June, 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Prognostic factors for relapse in stage I seminoma managed by surveillance or adjuvant carboplatin: A multivariate analysis on 588 cases
Authors: J. Aparicio, J. Garcia-Puche, M. Lomas, F. Carabantes, S. Vazquez, C. Crespo, M. Climent, A. Murias, A. Oltra, E. Barrajon
Journal: Journal of Clinical Oncology (2006)

4552 Background: The availability of reliable prognostic factors for relapse in stage I seminoma would allow a better patient stratification for individually tailored therapies. We performed a pooled analysis of patients included in two consecutive risk-adapted protocols. Methods: Between 1994 and 2004, 588 cases were prospectively registered. Median patient age was 33 years, median tumor size was 45 mm, serum BHCG levels were elevated preoperatively in 14.6%, and rete testis invasion was present in 26.9%. Three hundred and four patients (51.7%) with risk factors received two courses of adjuvant carboplatin, whereas 284 (48.3%) without these criteria were managed by surveillance. After a median follow-up of 48 months (range, 12–144), 43 relapses (7.3%) have occurred. Five-year disease-free survival was 92.3%. Univariate (log rank) and multivariate (Cox regression) analyses of prognostic factors for relapse were performed. Results: Relapses were less frequent after carboplatin treatment (3% vs 12%, p &lt; 0.0001). Statistically significant, independent predictors of relapse were: 1) rete testis invasion and age (&lt;30 years) in the whole series; 2) rete testis invasion for patients treated with adjuvant chemotherapy; and 3) tumor invasion beyond the albuginea and microvessel neoplastic invasion (defining 1997 AJCC pT2–4 staging) for patients managed by surveillance. In contrast, tumor size, histologic subtype (anaplastic), and serum preoperative BHCG levels were not associated with prognosis. Conclusions: Invasion of the rete testis and age (&lt;30 years) represent high-risk factors for patients with clinical stage I testis seminoma, independently of the treatment selected. These two features, in combination with pathologic T2–4 staging, could improve patient selection for risk-adapted therapies. No significant financial relationships to disclose.
Cooling Off Hot Flashes
Authors: Vered Stearns, Daniel F. Hayes
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.6.1436 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11896087 Cooling Off Hot Flashes Vered StearnsxVered StearnsSearch for articles by this author , Daniel F. HayesxDaniel F. HayesSearch for articles by this author Show More University of Michigan Comprehensive Cancer Center, Ann Arbor, MI https://doi.org/10.1200/JCO.2002.20.6.1436 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Abstract 13892: Therapeutic Suppression of Parvovirus B19 Replication with the Thymidine Analog Telbivudine Improves Clinical Outcome in Chronic Myocarditis and Reduces Apoptosis in Circulating Angiogenic Cells
Authors: Uwe Kuehl, Thomas Zobel, Heinz-Peter Schultheiss, Claus-Thomas Bock, Caroline Schmidt-Lucke
Journal: Circulation (2012)

Parvovirus B19 (B19V) is a causative agent of inflammatory cardiomyopathy and impaired cellular endothelial regeneration with consecutive endothelial dysfunction and microvascular disease. B19V was recently identified as strong inductor of apoptosis with impaired function of circulating angiogenic cells. Since as yet no therapeutic option for chronic B19V infection exists, we tested whether antiviral treatment with the thymidine analog telbivudine was effective on clinical outcome in B19V-cardiomyopathy and in suppressing B19V replication  in vitro . Patients (6 male, 2 female) with B19V associated chronic myocarditis were enrolled in a pilot trail to receive 600 mg o.d. of telbivudine for 6 months. Transcriptional activity of B19V was silenced in all but one patient after end of telbivudine therapy resulting in a significant suppression of B19V load in endomyocardial biopsies (EMB; 2245 to 629 genome equivalents (GE/µg isolated nucleic acids; p 2  on immunohistochemical analysis. Left ventricular ejection fraction improved significantly from 45% to 55% (p in vitro  data showed suppressed B19V replication after 48 hours. Pretreatment of early outgrowth endothelial progenitor cells and endothelial colony forming cells with telbivudine resulted in a significant reduction of apoptosis  in vitro  (39% and 60%, both p
SIGNIFICANT HEMOGLOBIN (HB) DECLINE DURING PEGYLATED INTERFERON AND RIBAVIRIN THERAPY IN HCV GENOTYPE 1 IS ASSOCIATED WITH SUSTAINED VIROLOGIC RESPONSE (SVR): AN ANALYSIS FROM THE CHARIOT STUDY
Authors: W Sievert, GJ Dore, GW McCaughan, M Yoshihara, DH Crawford, W Cheng, M Weltman, W Rawlinson, B Rizkalla, PI McCloud, SK Roberts
Journal: Hepatology (2009)
Airway eosinophils in older teenagers with outgrown preschool wheeze: a pilot study
Authors: Lucy Marshall, Caroline S. Beardsmore, Anina M. Pescatore, Claudia E. Kuehni, Erol A. Gaillard
Journal: European Respiratory Journal (2015)

Preschool wheezing affects one-third of all children growing up in the UK [1]. It varies in clinical presentation and severity, and there is evidence to suggest the co-existence of different wheeze phenotypes [2], some of which have been associated with adult asthma and chronic obstructive pulmonary disease [3]. Using data from the Leicester Respiratory Cohort studies [4], we have previously applied objective data-driven methods to distinguish three distinct preschool wheeze phenotypes: "atopic" and "non-atopic" persistent wheeze (PW) and transient viral wheeze (TVW) [5]. In children with PW, attacks of wheeze with and without colds were observed both at preschool age (0–5 years) and when followed-up at early school-age (4–8 years). Children with TVW, triggered predominantly by colds, had symptoms at age 0–5 years but not at age 4–8 years. Prognosis 5 years later (aged 8–13 years) was markedly better in children with TVW compared to the two PW phenotypes [6]. Teenagers with outgrown childhood wheeze display low level eosinophilic airway inflammation and lung function deficit <http://ow.ly/REaMc>
Interleukin-6 as a therapeutic target in advanced ovarian cancer.
Authors: J. I. Coward, H. Kulbe, D. Leader, M. Quigley, R. Thompson, A. Leinster, J. Nemeth, J. Vermeulen, I. McNeish, F. Balkwill
Journal: Journal of Clinical Oncology (2010)

5089 Background: The inflammatory cytokine IL-6 is a major component of an autocrine cytokine network in human ovarian cancer that influences angiogenesis, a stromal signature and leukocyte infiltration. Methods: We have used tissue culture experiments, animal models and data from a phase II clinical trial in women with advanced ovarian cancer to investigate the therapeutic potential and mechanisms of action of CNTO328, an antibody that neutralises IL-6. Results: In tissue culture, CNTO328 had no effect on growth or survival of ovarian cancer cells that expressed IL-6 receptors and constitutively secreted the ligand. However, it inhibited constitutive production of IL-6 and other inflammatory cytokines and chemokines, including TNF-α, IL-8, IL-1β and CCL2 by the malignant ovarian cells. In intraperitoneal ovarian cancer xenograft models, CNTO328 reduced tumour growth and angiogenesis and decreased transcription of inflammatory cytokines in the tumour microenvironment. Of eighteen patients with advanced, platinum-resistant ovarian cancer treated with CNTO328 (5.4 mg/kg every 2 weeks) in a single arm phase II trial, there was one partial response, as defined by combined RECIST/CA125 criteria and seven patients with stable disease. Baseline plasma TNF-α, IL-8, VEGF, β2 microglobulin and CRP were significantly lower in patients who had stable disease or partial response. After six weeks therapy, plasma levels of several cytokines were either stable or decreased in patients who had clinical benefit from the anti-IL-6 treatment and TNF-α and IL-8 were significantly lower in this group than in those who progressed. Plasma TNF-α, IL-8, VEGF and ascites TNF-α, IL-8, CCL2 and IL-1β levels showed a strong decline in the patient with a partial response. Four of the eighteen patients completed 6 months of treatment and this included the partial responder who had continued decreases in plasma IL-8, VEGF and CCL2 during this period. Conclusions: IL-6 antagonists may have a role to play in the treatment of ovarian cancer. Their actions involve inhibiting production of inflammatory cytokines, chemokines and angiogenic factors that have tumour-promoting actions in the ovarian cancer microenvironment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Centocor Ortho Biotech Centocor Ortho Biotech Centocor Ortho Biotech
C-reactive protein and interleukin-6 as markers of systemic inflammatory response and as prognostic factors for metastatic colorectal cancer. Data from the randomized phase III NORDIC-VII study.
Authors: Maria Thomsen, Christian Kersten, Halfdan Sorbye, Eva Skovlund, Tone Ikdahl, Julia S. Johansen, Per Pfeiffer, Bengt Glimelius, Kjell Magne Tveit, Tormod Kyrre Guren
Journal: Journal of Clinical Oncology (2015)

3548 Background: A systemic inflammatory response (SIR) affects prognosis and treatment outcome in metastatic colorectal cancer (mCRC). The aim of the study was to explore the prognostic significance of several SIR-derived markers and the correlation between the best marker of SIR and plasma interleukin-6 (IL- 6). Methods: The study was based on data from the randomized phase III NORDIC–VII study (Nordic FLOX +/- cetuximab as first line treatment of mCRC). The effect of different markers of SIR, including modified Glasgow Prognostic Score (mGPS), derived Neutrophil Lymphocyte Ratio (dNLR), levels of platelets and levels of C-reactive protein (CRP) on survival were analyzed by Kaplan-Meier plots, log-rank test, and Cox Proportional Hazards model. Further, the relationship between CRP, IL-6 and RAS and BRAF mutation status was examined. Results: 374 patients were eligible for the comparison of markers of SIR and 393 were eligible for the final analysis related to CRP, IL-6 and RAF and BRAF mutation status.The prognostic significance of CRP was at least as good as the other markers of SIR. CRP together with IL-6 were selected for further investigation. Log-transformed CRP and IL 6 were highly correlated (r = 0.661, p < 0.001) and an increasing level of pretreatment CRP was associated with impaired survival. Stratified by CRP level ≤ 10, 11-30, 31-60, and > 60 mg/L, the different groups showed a median overall survival (OS) of 24.3, 20.6,17.1 and 12.3 months, respectively (HR = 1.34, 95% CI 1.22-1.48, p < 0.001), and had a median progression-free survival (PFS) of 8.9, 7.6, 8.2, and 6.6 months, respectively (HR = 1.21, 95% CI 1.10-1.33, p < 0.001). Furthermore, CRP levels had a similar influence on prognosis in subgroups of patients based on RAS and BRAF mutation status. Conclusions: This is the largest study analyzing markers of SIR in a population of homogenously treated mCRC patients. Increasing CRP values were associated with impaired prognosis and the prognostic significance of CRP is at least equal to that of other markers of SIR. CRP values were highly correlated with IL-6 levels and may be used as a marker for plasma levels of IL-6. Clinical trial information: NCT00145314.
Phase I/II study of daily irinotecan as radiation sensitizer for locally advanced pancreatic cancer
Authors: I. Martel-Lafay, F. Desseigne, D. Perol, P. Kaemmerlen, P. Meeus, H. Labrosse, P. Meunier, P. Peyrat, B. Vincent, S. Negrier, C. Carrie
Journal: Journal of Clinical Oncology (2005)

4182 Background: To determine the maximal tolerated dose (MTD) of daily irinotecan with radiotherapy (RT) in patients (pts) with locally advanced adenocarcinoma of the pancreas. Methods: Between 09/2000 and 07/2004, 21 pts with histologically proved adenocarcinoma of pancreas were included in this prospective phase I/II study. (All patients had ECOG ≤ 2, total bilirubin ≤ 1,5 x LSN, PN ≥ 1,5 109/l, platelets ≥ 100 000/mm3, ALAT/ASAT ≤ 1,5 x LSN). Irinotecan was administrated daily, 1 hour before RT session. Doses were escalated by increment of 2 mg/m2 every 3 pts for an initial dose of 6 mg/m2/day. RT was delivered at 2 Gy per session, 5 fractions per week to a total dose of 50 Gy to the doses tumor volume. Primary endpoint was toxicity; secondary endpoints were tumor objective response (OR) defined as complete or partial response, secondary operability and overall survival (OS). Inoperability was assessed by surgeon. All images were reviewed by a radiologist. OR rates were compared using the Fisher’s exact test. Results: 21 pts were entered over 4 years through 6 dose levels from 6 mg/m2/day. Sex ratio was 1:1, median age was 56 y. (range 44–71), Karnofsky score was ≥ 90 in 95%. Current median follow-up is 31 months. No dose limiting toxicity was yet observed (last level 16 mg/m2/day). One patient experienced grade 3 toxicity (ulcer perforation) at the first dose level. OR rates were 43%, 35% and 15% at 4 weeks, 4 and 7 months, respectively. 3/13 pts (23%) included within the 3 first levels (≤ 10 mg/m2/day) experienced an OR at 4 weeks, versus 6/8 (75%) in the levels > 10 mg/m2/day (p = 0.03). 3 pts underwent surgery because of control tumor. Median OS was 12 months (95% CI 11–14). Conclusions: MTD is not actually reached with 16 mg/m2/day of irinotecan and we carry on the dose escalation. Despite response rate is not the main aim of the study, results suggest that RT combined with a higher daily level of irinotecan could be associated with a better tumor control. No significant financial relationships to disclose.
Pediatric glioblastoma treatment and clinical outcome: An institutional experience.
Authors: S. Mallick, S. Goyal, T. Puri, N. Joshi, P. K. Julka, G. K. Rath
Journal: Journal of Clinical Oncology (2010)

e12513 Background: Pediatric glioblastoma is an aggressive and rare tumor of childhood. It differs from adult glioblastoma both in clinical presentation as well as molecular characteristics. Additionally, unlike adult glioblastoma, management is not standardized. We intended to study the clinical characteristics along with outcome of pediatric glioblastoma patients treated with adjuvant chemoradiation. Methods: We retrospectively evaluated 27 patients with a histopathologic diagnosis of intracranial glioblastoma, treated at our department in the period May 2003 to March 2009. Demographic and disease characteristics in this patient cohort were recorded, and their outcome with adjuvant therapy was analyzed. Results: Median age at presentation was 12 years, (range 7-21 years), with a male: female ratio of 5.25. Most common tumor location was cerebral hemispheres (frontal-8; temporal-7; parietal-7; thalamus-1). Extent of surgery varied from gross total excision (14) to partial excision (13). The chief complaint was seizures in 25.9%. All patients received adjuvant radiotherapy (60 Gray over 6 weeks). 74% patients received concurrent chemotherapy with radiation (temozolomide (75 mg/m2) = 16, carboplatin (AUC 2) = 2, paclitaxel (75 mg/m2) = 2, and 59% patients received post-radiation chemotherapy (temozolomide 150-200 mg/m2 D1-5 q4 weeks for 6 cycles). Median follow up duration was 10 months (range 3-36 months) overall and 11 months (range 6-36 months) for those who received adjuvant temozolomide. At last follow up, 7 patients were disease-free. Eleven patients progressed on therapy, median time to progression being 9 months (range 3-29 months). There were no grade 3/4 adverse events. Conclusions: Pediatric glioblastoma is a rare but aggressive disease. Our study had a median follow-up of 10 months. Concurrent chemoradiation incorporating temozolomide followed by post-radiation temozolomide is a feasible option in pediatric age group as well, with a possibility of better outcomes with standardized therapy and longer follow-up. No significant financial relationships to disclose.