tbuckley/cabot-search huggingface dataset:
A phase III study of doxorubicin (A) versus cisplatin (P)/ interferonα-2b (I)/ doxorubicin (A)/ fluorouracil (F) combination chemotherapy (PIAF) for inoperable hepatocellular carcinoma (HCC)
Authors: W. Yeo, B. Zee, W. T. Leung, W. Y. Lau, T. S. K. Mok, H. T. M. Wong, J. Koh, S. Yu, A. T. C. Chan, P. J. Johnson
Journal: Journal of Clinical Oncology (2004)

4026 Background: Patients with inoperable HCC have a grave prognosis with a median survival of about 4 months. Single agent A has been commonly used but response rate (RR) has been <20%. A phase II study using combination PIAF has shown to be promising with RR of 26%. The objectives of this study were to compare A vs PIAF in patients with inoperable HCC. Methods: This is a phase III randomized study. Eligible patients include: histological proven inoperable HCC, adequate organ functions. Baseline radiological investigations were performed by CT (preferably) or US. They were randomized to either 3-weekly A(60mg/m2) or PIAF ( P 20mg/m2 d1–4,I 5 MU/m2 d1–4, A 40 mg/m2 d1, F 4000 mg/m2 d1–4) treatment. The primary endpoint was overall survival and the secondary endpoints were response rates and toxicities. Responses were graded according to WHO criteria. Toxicities were recorded according to NCI CTC. Results: The planned accrual was 200 patients (100 per arm). We report here the outcome of the first 180 patients. 170 patients were assessable for response; 4 patients did not have measurable disease, while 6 did not receive any chemotherapy. 82 of 89 in the A arm and 88 of 91 in the PIAF arm were assessable for response. Patients in A and PIAF arms received a median of 4 and 3 cycles of chemotherapy respectively. In A arm, there were 1 CR, 8 PR, 35 SD, 28 PD, 10 unknown; RR 10.9% (95%CI 4.2–17.7%). In PIAF arm, there were 18 PR, 30 SD, 19 PD, 21 unknown; RR 20.4% (95%CI 12.0–28.8%). There was no significant difference in the RR (p=0.091). Based on intention-to-treat analysis, the median survival of the A and PIAF arms were 7.1 (95%CI 5.4–9.8) and 8.4 (95%CI 6.2–12.8) months respectively (p=0.8701). Conclusions: There is no significant difference in response rates and overall survival between A and PIAF. The prognosis of patients with inoperable HCC remains poor. Toxicity data will be available at presentation. Further study using novel agents/combination is warranted. Acknowledgements: Interferon α-2b was supplied by Schering-Plough Division of SOL Ltd. No significant financial relationships to disclose.
Abstract 12626: Coupling Factor 6 Affects Lifespan By Reduced Autophagy Irrespectively Of Blood Pressure
Authors: Tomohiro Osanai, Kei Izumiyama, Takanori Sukekawa, Fumie Nishizaki, Akiko Suzuki, Makoto Tanaka, Hirofumi Tomita, Akihiro Kobayashi, Ken Okumura
Journal: Circulation (2012)

Backgrounds: Autophagy mediates protective effects in organ damage, and its reduction is associated with accelerated aging. We recently identified a circulating peptide coupling factor 6 (CF6) whic...
Oxaliplatin/CF/5-FU versus paclitaxel/CF/5-FU in patients with advanced gastric cancer: A phase II clinical trial
Authors: T. Lin, F. Xu, S. Wang, Y. He, W. Tian, Z. Guan
Journal: Journal of Clinical Oncology (2006)

14014 Background: Although many randomized trials of chemotherapy for advanced gastric cancer have been reported during the past two decades, no standard regimens worldwide have been established yet. Now Paclitaxel and Oxaliplatin have shown promising activity in advanced gastric cancer. We prospectively evaluated toxicity, efficacy and survival of Oxaliplatin /CF/5-FU versus Paclitaxel/CF/5-FU. Methods: Metastatic or locally advanced gastric cancer; performance status (PS) 0–2. Patients (pts) were enrolled and randomized into arm A with Oxaliplatin 100mg/m 2 , 5-FU 400 mg/m 2 bolus, FA 200 mg/m 2 2h, 5-FU 2500 mg/m 2 46h, q2w or into arm B with Paclitaxel 80 mg/m 2 , 5-FU 400 mg/m 2 bolus, FA 200 mg/m 2 2h, 5-FU 2500 mg/m 2 46h, q2w. Results: From 2000 to 2005, (A/B) 46/43 pts were enrolled into this study. Median age (52/50 y), gender, PS, localization and numbers of metastatic sites were comparable for both arms. Pts who were not chemotherapy naive in A/B (% of pts) were 41.3/33.3. All pts were eligible and evaluable for toxicity and response. Overall response (CR+PR) rate for A/B (% of pts): 37.0/47.2 (p&lt;0.05), tumor control rate (CR+PR+SD) 76.1/69.4(p&lt;0.05). Median time to progression (TTP) were for A/B: 6.0 and 3.2 months. And median survival time for A/B were 13.4 and 13.8 months. Grade 3/4 toxicities were for A/B (% of pts): neutropenia 10.9/5.6, thrombocytopenia 4.3/2.8, anemia 0/2.8, vomiting 8.7/2.8, neurotoxic 0/2. No treatment-related death occurred in A/B. Conclusions: Oxaliplatin /CF/5-FU and Paclitaxel/CF/5-FU are both effective and safe in advanced or metastatic gastric cancer. Though Oxaliplatin /CF/5-FU had better tumor control rate and median TTP, there was no difference between the arms in the median survival time. No significant financial relationships to disclose.
FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev as first-line treatment of metastatic colorectal cancer (mCRC): Updated survival results of the phase III TRIBE trial by the GONO group.
Authors: Chiara Cremolini, Fotios Loupakis, Gianluca Masi, Vittorina Zagonel, Francesca Bergamo, Lisa Salvatore, Enrico Cortesi, Gianluca Tomasello, Monica Ronzoni, Francesco Pinta, Alberto Zaniboni, Giuseppe Tonini, Angela Buonadonna, Domenico Amoroso, Claudia Sonaglio, Alfonso De Stefano, Corrado Boni, Giacomo Allegrini, Luca Boni, Alfredo Falcone
Journal: Journal of Clinical Oncology (2015)

657 Background: The phase III TRIBE trial met its primary endpoint, by demonstrating that first-line FOLFOXIRI plus bev significantly prolongs PFS, as compared to FOLFIRI plus bev. Also RECIST response rate, early response rate and deepness of response were significantly increased. At the first statistical analysis, with a median follow-up of 32.2 months, OS results were considered preliminary. Methods: Between July 2008 and May 2011, 508 patients were randomized to either FOLFIRI plus bev (arm A, n=256) or FOLFOXIRI plus bev (arm B, n=252). Both treatments were administered for a maximum of 12 cycles followed by 5FU/bev until progression. Results: At a median follow-up of 48.1 months, 374 deaths were recorded (Arm A=200 vs. Arm B=174). Median OS for Arm B vs. Arm A was 29.8 vs. 25.8 months (HR=0.80, 95% CI, 0.65-0.98, p=0.030). Long-term survival rates are reported in Table 1. Treatment effect was consistent across all analyzed subgroups. Among clinical variables, ECOG performance status of 1 or 2, right-sided primary tumor, synchronous metastases, disease not confined to the liver, unresected primary tumor, high Kohne score negatively affected prognosis at univariate analyses. At an exploratory model accounting for these variables, adjusted HR for treatment effect on OS was 0.77 (95% CI, 0.61-0.96, p=0.020). Conclusions: FOLFOXIRI plus bev improves survival of mCRC patients, as compared to FOLFIRI plus bev. The estimated 5-years OS rate of patients treated with FOLFOXIRI plus bev was equal to 24.9%, with an absolute benefit of 12.5% compared to controls. FOLFOXIRI plus bev represents a valuable option for the upfront treatment of mCRC. Clinical trial information: NCT00719797. [Table: see text]
BAY 43–9006 as single oral agent in patients with metastatic breast cancer previously exposed to anthracycline and/or taxane
Authors: A. Moreno-Aspitia, D. W. Hillman, M. Wiesenfeld, T. J. Hobday, K. M. Rowland, D. W. Northfelt, K. S. Tenner, F. M. Palmieri, E. A. Perez
Journal: Journal of Clinical Oncology (2006)

577 Background: BAY 43–9006 targets the ras/raf signaling pathway and inhibits VEGFR-2, VEGFR-3 and or PDGFR-β growth factors. A study was conducted to assess anti-tumor activity and the toxicity profile in patients (pts) with metastatic breast cancer (MBC). Methods: A two-stage phase II study was conducted with pts with MBC who had measurable disease and were candidates for 1 st or 2 nd line chemotherapy and had previously received an anthracycline and/or a taxane in the neoadjuvant, adjuvant, or metastatic setting. Pts started with a dose of 400 mg twice daily on days 1–28 of each 4 week cycle. Based on interval adverse events (AEs), a dose reduction was considered as 400 mg given one time daily. Primary endpoint was tumor response defined as a complete or partial response (PR) according to RESIST. The study required 40 pts, but was to be terminated if 0 or 1 responses occurred among 1 st 20 eligible pts. Results: 23 pts enrolled with a median age of 54 (range 37–70) but 3 were declared ineligible. All 23 pts were included in all analyses except efficacy analysis as stated per protocol. Fifteen (65%) had visceral metastasis; 22 (96%) had prior anthracycline treatment (tx); 16 (70%) had prior taxane tx.; 10 (44%) had received prior chemotherapy for metastatic disease and 14 (61%) had a prior relapse free interval of 12 months (mos) or more. Pts received tx for a median of 2 cycles (range 1–8) with a median follow-up of 7.2 mos. Dose reductions were due to dermatitis/skin rash (3), hand/foot skin reaction (2), hypertension (1) and cramping hands/feet (1). No grade 4 AEs occurred and grade 3 AEs included acne (2), hand/foot skin reaction (1), neutropenia (1), cough (1), wound infection (1), and prolonged PTT (1). Among the 20 pts eligible for efficacy analysis one pt (5%; 95% CI 0.5–20.5%) achieved a PR with duration of 3.6 mos and one pt achieved stable disease for at least 6 mos. The 6-month overall survival rate was 81% and the progression-free survival rates were 53% at 2 mos, 24% at 4 mos and 6% at 6 mos. Median time to progression was 2 mos. Based on the lack of sufficient response, we did not proceed with the 2nd stage of this study. Conclusion: Treatment with oral BAY 43–9006, while well tolerated, does not have sufficient activity to warrant further testing as a single agent in this disease setting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech
Mabthera (Rituximab) Plus CVP Chemotherapy for First-Line Treatment of Stage III/IV Follicular Non-Hodgkin’s Lymphoma (NHL): Confirmed Efficacy with Longer Follow-Up.
Authors: Philippe Solal-Celigny, Kevin Imrie, Andrew Belch, Katherine Sue Robinson, David Cunningham, Antonio Rueda, John Catalano, Fritz Offner, Jan Walewski, João Raposo, Paul Smith, Robert Marcus
Journal: Blood (2005)
Dual Inhibition of Aurora and FLT3 Kinases by CCT137690: A Novel Treatment Strategy Against FLT3-ITD Positive AML In Vitro and In Vivo
Authors: Andrew S Moore, Amir Faisal, Vassilios Bavetsias, Chongbo Sun, Butrus Atrash, Melanie Valenti, Alexis de Haven Brandon, Sian Avery, Florence I Raynaud, Paul Workman, Andrew DJ Pearson, Julian Blagg, Suzanne A Eccles, Spiros Linardopoulos
Journal: Blood (2010)
Impact of a novel nurse-led prechemotherapy education intervention (ChemoEd) on patient distress, symptom burden, and treatment-related information and support needs: results from a randomised, controlled trial
Authors: S. Aranda, M. Jefford, P. Yates, K. Gough, J. Seymour, P. Francis, C. Baravelli, S. Breen, P. Schofield
Journal: Annals of Oncology (2011)
Multi-center study evaluating circulating tumor cells (CTCs) as a surrogate for survival in men treated for castration refractory prostate cancer (CRPC)
Authors: J. Moreno, J. S. DeBono, D. Shaffer, B. Montgomery, M. C. Miller, H. Tissing, G. Doyle, L. W. Terstappen, K. J. Pienta, D. Raghavan
Journal: Journal of Clinical Oncology (2007)

5016 Background: Monitoring CTCs in patients undergoing therapy for metastatic breast cancer is an effective means to predict outcome and monitor treatment. The primary endpoint of this prospective multi-center study was to demonstrate a significant relation between the presence of CTCs and survival in men treated for CRPC. Methods: 276 patients with diagnosed CRPC, PSA progression, and an ECOG score of 0–2 about to begin initial or salvage chemo and/or combination therapy were enrolled. CTCs were enumerated with the CellSearch System in blood drawn pre-treatment and monthly thereafter for up to 18 months. Patient data were collected and maintained by an independent CRO. Median overall survival (OS) was determined for patients with =5 CTC /7.5mL at baseline and specified intervals. Results: Of 240 evaluable patients, 142 (59%) are alive - mean follow-up 11.4 ± 4.4 months. Median OS (in months) and significance between the two groups (logrank p-value) at different time points after the initiation of therapy are indicated in the table . Median OS for 40 (19%) patients with a reduction of CTCs below 5 CTCs 2–5 weeks after initiation of therapy was significantly longer as compared to those 78 (38%) patients that remained above 5 CTCs (&gt;20 vs. 9.3mth, p=0.0000) and was not significantly different from the 83 (40%) patients with 20 vs. &gt;20mth, p=0.2725). In multivariate analyses, which included stage at diagnosis, age, ECOG, Gleason score, LDH, Alkaline Phosphotase, and PSA, CTCs remained the most significant independent predictor of outcome. Conclusions: CTC levels in CRPC patients are a strong predictor of OS. The persistence of CTCs after initiation of therapy suggests that the patients are deriving less than optimal benefit from their current therapy. CTC levels may be a valid surrogate end-point in monitoring response to chemotherapy. [Table: see text] No significant financial relationships to disclose.
Increased incidence of HLA-DR3+ individuals amongst HER2/neu expressing breast cancer patients
Authors: M. G. Carmichael, G. E. Peoples, L. C. Benevides, J. D. Gates, R. Patil, A. Amin, Y. H. Jama, D. Craig, S. Ponniah, J. P. Holmes
Journal: Journal of Clinical Oncology (2008)

22215 Background: HER2/neu is a tumor associated antigen that is over-expressed in several epithelial cancers. HER2/neu-specific immunity can prevent breast cancer in animal models. Immune surveillance against HER2/neu is a potential defense mechanism against cancer and is pursued as immunotherapy of breast cancer. Prior studies demonstrated that peptides from HER2/neu display varying binding affinities to different MHC Class II DR alleles. HLA-DR3 had the lowest affinity for HER2/neu peptides suggesting that DR3+ individuals may have reduced immunosurveillance against HER2/neu and thereby be susceptible to developing HER2/neu related cancers. We hypothesized that the presence of the DR3 allele may predispose patients to develop breast cancer, and if true, might expect to find higher numbers of DR3+ individuals among BrCa patients compared to the general population. Methods: Serologic and molecular testing for HLA-DR3 was performed on 52 HER2/neu+ (IHC 1–3+) breast cancer patients. We compared clinicopathologic features of disease in the DR3+ and DR3- groups. Results: The HLA-DR3 haplotype frequency in the general population is reported at 13.2%. We identified the DR3 haplotype in 17 of 52 (33%) patients, making it more than twice as prevalent in BrCa patients. The DR3+ (n=17) and DR3- (n=35) groups had similar clinicopathologic features (DR3+ vs. DR3-, respectively) including median age (53 vs. 55 years), % patients ≥ stage 2 (78% vs. 75%), % patients ≥ grade 2 (63% vs. 66%). There was a trend toward decreased HER2/neu over-expressing (IHC 3+) tumors in the DR3+ group (12%) compared to the DR3- group (31%, p=0.1). Conclusions: We have detected a disproportionate representation of HLA- DR3+ individuals in our population of HER2/neu-expressing breast cancer patients (33% vs. an expected 13%). Although it appears that HLA- DR3+ individuals may be at an increased risk of developing breast cancer, their prognostic factors are not better or worse. Further studies to evaluate a potential defect in HER2/neu-related immunosurveillance (serum antibodies and CD4 T-cell responses) are planned. No significant financial relationships to disclose.
HER2 testing: A health economics perspective on alternative test strategies.
Authors: J. A. Lee, M. F. Press
Journal: Journal of Clinical Oncology (2010)

606 Background: Active deliberation exists regarding alternative strategies for HER2 testing to target trastuzumab therapy that generally focuses on IHC, FISH or combination strategies. Expanded use of lapatinib increases the clinical and economic importance of the discussion; additional test methods like quantitative reverse transcription-polymerase chain reaction and chromogenic in situ hybridization provide additional options for consideration. Methods: An algebraic model comparing alternative test strategies (IHC only, FISH only, reflex to FISH, and a hypothetical perfect Gold Standard [GS]) and published results regarding the costs and benefits of adjuvant trastuzumab therapy was developed. Sensitivity to test accuracy and price, and assumed costs and benefits of therapy were performed, including comparison to GS. Results: A primary FISH test strategy is cost effective relative to other test strategies using IHC even if the cost difference between IHC and FISH is $400. More than a 2.0% reduction in specificity with 99.5% overall accuracy relative to a hypothetical GS, results in increased health care costs. More than a 3.0% reduction in sensitivity with 99.3% overall accuracy relative to a GS results in the GS test being cost effective with a $400 price differential. As the price of the GS declines relative to alternative strategies, the accuracy of the alternative strategies must improve to be cost effective or cost saving. Conclusions: Given the increasing use of adjuvant trastuzumab therapy, and its cost relative to HER2 testing, small reductions in specificity relative to a hypothetical gold standard may substantially increase health costs or reduce cost effectiveness. Given the benefits of adjuvant trastuzumab therapy, small reductions in test sensitivity may result in substantial lost opportunities in improved quality and length of life. Analysis of alternative HER2 test methods must consider health system and quality of life impact. The focus of HER2 test research should be on improving response to therapy rather than less costly HER2 test methods. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories, Genentech, GlaxoSmithKline, Ventana Medical Systems Abbott Laboratories Abbott Laboratories, Genentech, GlaxoSmithKline, Ventana Medical Systems
Design and Measurement of Nonislet-Specific Autoantibodies for the Type 1 Diabetes Genetics Consortium Autoantibody Workshop
Authors: Beena Akolkar, Joan Hilner, Concepcion R. Nierras
Journal: Diabetes Care (2015)

The Type 1 Diabetes Genetics Consortium (T1DGC) comprised groups of investigators from many countries throughout the world, with a common goal of identifying genes predisposing to type 1 diabetes. The T1DGC ascertained and collected samples from families with two or more affected siblings with type 1 diabetes and generated a broad array of clinical, genetic, and immunologic data. The T1DGC Autoantibody Workshop was designed to distribute data for analyses to discover genes associated with autoantibodies in those with type 1 diabetes. In the T1DGC-affected sibling pair families, three T1DGC Network laboratories measured antibodies to the islet autoantigens GAD65 and the intracellular portion of protein tyrosine phosphatase (IA-2A). The availability of extensive genetic data provided an opportunity to investigate the associations between type 1 diabetes and other autoimmune diseases for which autoantibodies could be measured. Measurements of additional nonislet autoantibodies, including thyroid peroxidase, tissue transglutaminase, 21-hydroxylase, and the potassium/hydrogen ion transporter H+/K+-ATPase, were performed by the T1DGC laboratory at the Barbara Davis Center for Childhood Diabetes, Aurora, CO. Measurements of all autoantibodies were transmitted to the T1DGC Coordinating Center, and the data were made available to members of the T1DGC Autoantibody Working Groups for analysis in conjunction with existing T1DGC genetic data. This article describes the design of the T1DGC Autoantibody Workshop and the quality-control procedures to maintain and monitor the performance of each laboratory and provides the quality-control results for the nonislet autoantibody measurements.
Mulicenter phase II study of gemcitabine and carboplatin combination therapy for patients with metastatic carcinoma of unknown primary site: final results
Authors: K. B. Pittman, I. N. Olver, C. S. Karapetis, D. Kotasek, T. J. Price, W. K. Patterson, D. M. Keefe, B. Koczwara, F. X. Parnis, D. Greer
Journal: Journal of Clinical Oncology (2005)

8142 Background: Cancer of unknown primary site (CUP) accounts for approximately 5% of cancer diagnoses. Numerous chemotherapy strategies have been evaluated in this setting, but the prognosis remains poor. The combination of Gemcitabine (G) and Carboplatin (C) has a broad range of activity and acceptable tolerability making it a potential treatment of CUP. We report the final results of a multicenter prospective phase 2 trial of the GC combination in patients with CUP treated in 4 cancer centers across Adelaide, South Australia. Methods: ECOG performance status 0–2 patients with histologically confirmed metastatic carcinoma in which the primary site of cancer was not evident after prospectively designated investigations (including upper and lower GI endoscopy) were treated with G 1000 mg/m2 IV days 1 and 8, and C AUC 5 IV on day 8 every 3 weeks to a maximum of 9 cycles. The primary endpoints were response rate, toxicity, and quality of life. Other endpoints included time to progression and overall survival. Results: Median follow-up is 25 months (range 10 - 41). 50 (23 male, 27 female) patients were enrolled, with a median age of 69 yrs. (range 41–83). 46% were ≥ 70 yrs. Alopecia was minimal and significant nausea/vomiting was rare. The major toxicity and efficacy results are illustrated in the table below. Conclusions: The GC regimen has significant activity in CUP, with excellent tolerability and maintenance of Quality of Life, especially in this predominantly poor prognosis elderly population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly
N-Terminal Pro–B-Type Natriuretic Peptide–Guided, Intensive Patient Management in Addition to Multidisciplinary Care in Chronic Heart Failure
Authors: Rudolf Berger, Deddo Moertl, Sieglinde Peter, Roozbeh Ahmadi, Martin Huelsmann, Susan Yamuti, Brunhilde Wagner, Richard Pacher
Journal: Journal of the American College of Cardiology (2010)