bluuebunny/crossref_metadata_2025_split huggingface dataset:
Period 2 (PER-2) biologic profile in advanced colorectal cancer (ACC) patients (pts).
Authors: Melucci Elisa , Torsello Angela , Ruzzo Annamaria , Sperduti Isabella , Giacomini Elisa , Zeuli Massimo , Gelibter Alain , Ferraresi Virginia , Diodoro Maria G. , Magnani Mauro , Mottolese Marcella , Cognetti Francesco , Garufi Carlo ,   AIRC Project 11770
Published: March 2020

e22206 Background: Circadian rhythms modulated by clock genes expression as the Period genes (PER-1, PER-2, PER-3) are involved in cancer growth. PER-2 loss in colorectal cancer cell lines and in animal models increases tumorigenesis by β-catenin and cyclin D activation (Wood P, Cancer Res 2008). PER-2 loss in ACC pts was linked to a worse prognosis (Iacobelli S, ASCO 2008). The aim of our study was to identify a PER-2 biological profile related to proliferative indexes and treatment activity. Moreover miRNA related to clock genes were studied as miR-219, target of CLOCK and B-MAL1, miR-206 which affect mammalian circadian clock, miR-132 acting at the SCN level. Methods: We retrospectively evaluated 59 ACC pts, treated with first line chronomodulated triplet combination (Irinotecan+Oxaliplatin+Folinic Acid+5-Fluorouracil) ± Cetuximab. Immunostaining for PER-2, EGFR, ERβ1, ERβ2, Cyclin D1, β-catenin, K-RAS and B-RAF mutations, miRNAs -206, -132, -192, -194, and -219 evaluated on FFPE tumor tissues and their expression levels by quantitative PCR were examined. Results: Clinical data: M/F 32/27; median age 57 y; liver involvment 53%; Cetuximab use: 38%; liver resection: 42%; response to first line chemotherapy: PR 61%, SD 25.4%, PD 10.2%; pts 2.4% not evaluable. Biological data: PER-2 negative (-) /positive (+) 44/56%; EGFR (+)/(-) 54/46%; KRAS wt/mut 75/25%; ERβ1 (-)/(+) 36/65%; ERβ2 (-)/(+) 39/61%; Cyclin D1 (-)/(+) 51/49%; β-catenin(-)/(+) 31/69%. PER-2(-) patients expressed more frequently EGFR (73%) (p>0.0001), ERβ1 (77%) (p=0.07), ERβ2 (88.5%) (p>0.0001), Cyclin D1 (69.2%) (p=0.06) and β-catenin (84.6%) (p=0.02). PER-2(-) was also associated to high miR-206, miR-192 and miR-219 expression. Explorative multiple correspondence analysis showed response to chemotherapy related to a profile including PER-2 (+), EGFR (-), ERβ1 (-), ERβ2 (-), β-catenin (-) and low expression of miR-206. Conclusions: Our data confirmed that: 1) PER-2 loss was associated to activation of cell proliferation confirming in vitro data; 2) PER-2 expression was linked to negative activation of cell proliferation, low miR-206 expression and response to chemotherapy.
Association of cyclin D2 downregulation with adverse prognostic factors and survival: Analysis of D-type cyclins, cyclin E1, p27, and ki-67 mRNA in breast carcinomas.
Authors: Brizova Helena , Mrhalova Marcela , Kodet Roman 
Published: March 2020

e22208 Background: In a normal mammary gland D-type and E1 cyclins play a significant role in the cell cycle control. Not surprisingly, they are considered to have an oncogenic potential and belong among the most commonly overexpressed genes in breast cancer. Besides, cyclin D2 overexpression is associated with an inhibition of cyclin D1 phosphorylation and with an increase of the p27 inhibitor. Such a complex cell cycle regulation is realized at the quantitative level and results in the proliferation activity control. Therefore, we analyzed the molecules involved in the cell cycle regulation together with the proliferation marker Ki-67 at the quantitative level. Methods: We examined cyclin D1, D2, D3, E1, and p27 and Ki-67 mRNA level by qRT-PCR in 95 fresh frozen invasive ductal breast carcinomas and in 15 non-neoplastic breast tissues. In patients with the carcinoma we correlated the mRNA levels with the ERBB-2 positivity, estrogen and progesterone receptor status, proliferation rate, cyclin D1 protein expression, CCDN1 gene amplification, grade, lymph node status, tumor size and age at diagnosis. We looked for a correlation with overall survival and time to event in 70 patients with available long term follow-up data. Results: The only significant association found in this analysis related to cyclin D2. In comparison with non-neoplastic controls we observed cyclin D2 mRNA down-regulation in breast carcinomas and it was inversely correlated with a higher tumor grade and its greater size, which are considered as parameters related to a less favorable prognosis. Moreover, cyclin D2 mRNA down-regulation together with cyclin D1 and D3 up-regulation revealed a significant association with decreased overall survival and time to event in multivariate analysis. Conclusions: The data indicate that down-regulated cyclin D2 mRNA correlates with a greater malignant potential of breast carcinoma. Thus, establishing cyclin D2 mRNA level may be used as a prognostically relevant investigation and along with other prognostically related data it has a potential in helping to identify patients with an adverse prognosis. Support CZ.2.16/3.1.00/24022 and 00064203.
Randomized comparison of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment of KRAS-wildtype metastatic colorectal cancer: German AIO study KRK-0306 (FIRE-3).
Authors: Heinemann Volker , Fischer von Weikersthal Ludwig , Decker Thomas , Kiani Alexander , Vehling-Kaiser Ursula , Al-Batran Salah-Eddin , Heintges Tobias , Lerchenmueller Juergen , Kahl Christoph , Seipelt Gernot , Kullmann Frank , Stauch Martina , Scheithauer Werner , Hielscher Joerg , Scholz Michael , Mueller Sebastian , Schaefer Britta , Modest Dominik Paul , Jung Andreas , Stintzing Sebastian 
Published: March 2020

LBA3506 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.
Phase III trial of a 3-weekly versus 5-weekly schedule of S-1 plus cisplatin (SP) combination chemotherapy for first-line treatment of advanced gastric cancer (AGC): SOS study.
Authors: Ryu Min-Hee , Baba Eishi , Lee Kyung Hee , Boku Narikazu , Park Young Iee , Hyodo Ichinosuke , Nam Byung-Ho , Esaki Taito , Ryoo Baek-Yeol , Song Eun-Kee , Cho Sanghee , Lee Sung Sook , Kang Won Ki , Yang Sung Hyun , Zang Dae Young , Shin Dong Bok , Park Sook Ryun , Shinozaki Katsunori , Takano Toshimi , Kang Yoon-Koo ,   on behalf of SOS Investigators
Published: March 2020

LBA4024 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 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 Monday edition of ASCO Daily News.
Duration of androgen deprivation therapy in high-risk prostate cancer: A randomized trial.
Authors: Nabid Abdenour , Carrier Nathalie , Martin André-Guy , Bahary Jean-Paul , Souhami Luis , Duclos Marie , Vincent Francois , Vass Sylvie , Bahoric Boris , Archambault Robert , Lemaire Céline 
Published: March 2020

LBA4510 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June 3, 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 Monday edition of ASCO Daily News.
Interim analysis of The Spanish Lung Cancer Group (SLCG) BRCA1-RAP80 Expression Customization (BREC) randomized phase III trial of customized therapy in advanced non-small-cell lung cancer (NSCLC) patients (p) (NCT00617656/GECP-BREC)
Authors: Moran Teresa , Cobo Manuel , Domine Manuel , Sanchez-Ronco Maria , Bover Isabel , Provencio Mariano , Massuti Bartomeu , Vergnenegre Alain , Lopez-Vivanco Guillermo , Robinet Gilles , Insa Amelia , Majem Margarita , De Las Penas Ramon , Sala María Ángeles , Isla Dolores , Baize Nathalie , Garde Javier , Chaib Imane , Camps Carlos , Rosell Rafael ,   Spanish Lung Cancer Group
Published: March 2020

LBA8002 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June 3, 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 Monday edition of ASCO Daily News.
Nintedanib (BIBF 1120) plus docetaxel in NSCLC patients progressing after one prior chemotherapy regimen: Results of Lume-Lung 1, a randomized, double-blind, phase III trial.
Authors: Reck Martin , Kaiser Rolf , Mellemgaard Anders , Douillard Jean Yves , Orlov Sergey , Krzakowski Maciej Jerzy , Von Pawel Joachim , Gottfried Maya , Bondarenko Igor , Liao Meilin , Barrueco Jose , Gaschler-Markefski Birgit , Novello Silvia 
Published: March 2020

LBA8011 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June 3, 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 Monday edition of ASCO Daily News.
Alliance A091103: Multicenter phase II study of the angiopoietin-1 and -2 peptibody trebananib for the treatment of angiosarcoma.
Authors: D'Angelo Sandra P. , Mahoney Michelle R. , Van Tine Brian Andrew , Adkins Douglas , Grosse Perdekamp Maria T. , Condy Mercedes M. , Hartley Eliza , Antonescu Cristina R. , Schwartz Gary K. , Tap William D. ,   Alliance Clinical Trials in Oncology Group
Published: March 2020

TPS10592 Background: Angiosarcomas (ASs) are rare, aggressive, malignant endothelial cell tumors that constitute 1% to 2% of all soft tissue sarcomas with 5-year survival of 35%. Cytotoxic agents have demonstrated response rates of about 15%. Gene-array data from MSKCC has revealed up-regulation of endothelial associated genes, including active members of the angiopoietin system e.g., Tie2 and Angiopoietin 2 (Ang2). Trebananib (AMG386) is a novel agent that targets Ang1 and Ang2. We hypothesize that inhibition of angiopoietin 2 with trebananib will be an effective therapy in patients (pts) with AS. Methods: This CTEP sponsored, investigator initiated, multi-center phase II study uses trebananib, in pts with AS having metastatic/unresectable AS and conducted through the Alliance for Clinical Trials in Oncology (Alliance A091103). Pts must have adequate performance status, organ function, and measurable disease (RECIST v1.1). Patients are treated with trebananib 30mg/kg d1, 8, 15, and 22 every 28 days until either progressive disease or unacceptable toxicity. The primary endpoint is objective overall response rate (ORR) via RECIST v1.1. Secondary endpoints include the evaluation of progression-free survival (PFS) and overall survival (OS). Translational objectives include correlation of ORR, PFS and OS with i. baseline and post-treatment expression of Ang2 and Tie2 by immunohistochemistry (IHC), ii. serum levels of Ang1 and Ang2, iii. baseline and post-treatment phospho-receptor tyrosine kinase (p-RTK) status of Tie2, VEGFR-2, PI3K, MEK and MAPK, and iv. mutational status of VEGFR-2 and amplification of MYC/FLT4. A Simon Optimal two-stage phase II study design is used and one confirmed response in the first 12 pts expands enrollment to 25. Pre- and post-treatment biopsies will be performed in up to 10 pts treated at MSKCC. Enrollment began in July 2012. As of January 2013, 7 pts have been recruited. Clinicaltrials.gov#: NCT01623869. Funded by the Alliance Clinical Trials in Oncology. NIH Grant CA-25224. Clinical trial information: NCT01623869.
A randomized, phase II trial of AEZS-108 in chemotherapy refractory triple-negative (ER/PR/HER2-negative) LHRH-R positive metastatic breast cancer.
Authors: Buchholz Stefan , Engel Joerg , Schally Andrew V. , Seitz Stephan , Ortmann Olaf , Emons Guenter , Mahtani Reshma L. , Gluck Stefan , Vogel Charles L. , Montero Alberto J. 
Published: March 2020

TPS11124 Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is clinically negative for expression of estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor-2 (HER2). It is characterized by its unique molecular profile, aggressive behavior, distinct patterns of metastasis, and lack of commercially available targeted therapies. Chemotherapy has been the mainstay of treatment for women with TNBC, but this current standard-of-care is suboptimal. AEZS-108 is an LHRH-cytotoxic hybrid drug whose rational design covalently couples the carrier D-Lys6-LHRH (an LHRH agonist) to the cytotoxic doxorubicin radical. Because LHRH receptors are expressed in a majority of TNBC, AEZS-108 represents a novel way to selectively deliver cytotoxic chemotherapy in patients with TNBC via a new therapeutic target. Methods: In this open label randomized two-arm multicenter phase II study, patients will be randomized in a 1:1 ratio into one of the two treatment arms: AEZS-108 (267 mg/m2 every 21 calendar days) [Arm A] or SSC (standard single agent cytotoxic chemotherapy [Arm B]) at discretion of treating oncologist cycled every 21 calendar days. Stratified randomization will be used with number of prior lines of therapies (1-2 vs. >2), ECOG performance status 0-1 vs. 2, and liver metastases (absent vs. present). Analysis of the main study endpoint, TTP, will follow a group sequential design with two interim analyses, including the final analysis. O’Brien Fleming stopping boundaries will be used. The primary endpoint is to evaluate the median time to progression (TTP) of AEZS-108 in patients with chemotherapy resistant advanced TNBC treated with AEZS-108 in relation to patients receiving standard single agent cytotoxic chemotherapy. Secondary endpoints include: overall response, clinical benefit, duration of response, overall survival, toxicity profile and quality of life (QoL). Clinical trial information: NCT01698281.
The ENCHANT-1 trial (NCT01677455): An open label multicenter phase II proof of concept study evaluating first-line ganetespib monotherapy in women with metastatic HER2-positive or triple-negative breast cancer (TNBC).
Authors: Awada Ahmad , Rodriguez Angel Augusto , Kong Anthony , Erban John Kalil , Cortes Javier , Mano Max S. , Perez Edith A. , El Hariry Iman , Vukovic Vojislav M. , Teofilovici Florentina , Yalcin Ilker , Bradley Robert , Cameron David A. 
Published: March 2020

TPS1136 Background: Hsp90 is a molecular chaperone protein required for the stabilization and activation of many proteins, referred to as Hsp90 ‘clients’, including those commonly implicated in breast tumorigenesis such as HER2, EGFR, ER, PI3K, AKT, P53 and VEGFR. Ganetespib is a novel triazolone inhibitor of Hsp90 being studied in over 20 clinical trials, with over 700 patients treated to date. Ganetespib is ~50x more potent than 1st-generation Hsp90 inhibitors, and has been well tolerated in clinical trials with a favorable safety profile. Mild to moderate, transient diarrhea is the most common adverse event associated with ganetespib infusion and is manageable with appropriate supportive care. Ganetespib has shown activity in preclinical models of HER2+, ER+/PR+ and triple negative breast cancer (TNBC). In a phase I trial, ganetespib demonstrated single-agent clinical activity in HER2+ disease with an objective response rate (ORR) of 15% and a disease stabilization rate of 46% in heavily pretreated patients. This efficacy-screening study is designed to provide further evidence of ganetespib activity and identify potentially predictive biomarkers in metastatic breast cancer. Methods: The ENCHANT-1 trial is an international, first-line Phase II study in two cohorts of breast cancer patients: Cohort A, HER2 amplified (n=35), and Cohort B, TNBC (n=35). HER2+ patients must have received prior anti-HER2 therapy in the adjuvant setting. Patients are treated with ganetespib at 150 mg/m2 twice weekly on a three out of four-week regimen. Primary endpoint: ORR assessed using RECIST1.1 criteria. Key secondary endpoints include metabolic effects as assessed by PET/CT at week 3. Tumor genetic signature and proteomic profiling are performed on patient’s tumors in an effort to develop biomarkers of response. At the time of submission 6 patients have been enrolled into this study. Clinical trial information: NCT01677455.
Adjuvant phase III trial to compare intense dose-dense adjuvant treatment with EnPC to dose dense, tailored therapy with dtEC-dtD for patients with high-risk early breast cancer (GAIN-2).
Authors: Moebus Volker , Forstbauer Helmut , Wachsmann Grischa , Schneeweiss Andreas , Ober Angelika , von Abel Ekkehard , Krabisch Petra , Hoeffkes Heinz-Gert , Kast Karin , Christensen Bernd , Niedermeier Michael , Deryal Mustafa , Uleer Christoph , Fauster Yvonne , Goehler Thomas , Loibl Sibylle , Nekljudova Valentina , Von Minckwitz Gunter ,   German Breast Group
Published: March 2020

TPS1137 Background: Intense dose-dense (idd) chemotherapy (CT) significantly improves overall survival in breast cancer patients. Two preceding trials explored iddETC vs a dd combination of EC-TX (GAIN) and dtEC-dtD vs conventional dosed FEC-D (Panther). Nab-paclitaxel (nP) provides a better toxicity profile and higher efficacy compared to solvent based taxanes and might be preferred in an idd regimen. Methods: This is a multicenter, prospective, randomized, open-label phase III trial comparing iddEnPC or dtEC-dtD as adjuvant CT. Pts with uni- or bilateral primary high risk node-positive (N+) breast cancer (BC) and centrally confirmed ER/PR/HER2 and Ki-67 status can be included. Luminal A pts are only recruited with N+ ≥4. Randomization to iddEnPC or dtEC-dtD will be stratified by biological subtype defined by hormone receptor, HER2 and Ki-67. The iddEnPC arm will receive epirubicin (150mg/m2) q2w x3 followed by nP (260-330mg/m2, dose to be determined in run-in phase) q2w x3, followed by cyclophosphamide (2g/m2) q2w x3. The dtEC-dtD arm will receive EC (38-120/450-1200 mg/m2) q2w x4 followed after 1 wk rest by docetaxel (60-100mg/m2) q2w x4. GAIN-2 will compare toxicity and efficacy of an idd regimen (EnPC) vs a dd regimen with modification of single doses depending on individual hematological and non-hematological toxicities. Primary objective is invasive disease-free survival (IDFS). Secondary objectives are survival by other definitions, compliance, safety, side effects of taxanes and subgroup analyses (by 0-3, 4-9 or 10+ involved nodes and Ki-67). Efficacy analyses are planned 60 mths after end of accrual, safety interim analyses after 200 and 900 pts have completed CT. It was assumed that dtEC-dtD will achieve a 5-yr IDFS of 75% and ddEnPC will improve IDFS to 79% (HR 0.819) with a power of 80% (α=0.05, ß= 0.2).GAIN-2 is registered under NCT01690702 Results: 75pts were recruited since 1stOct 2012. Recruitment (in total 2886 pts) is planned for 36 mths in 80-100 sites in Germany. Run-in safety data to be presented. Conclusion: GAIN-2 will compare the efficacy of adjuvant iddEnPC and dtEC-dtD in pts with early N+ BC. Clinical trial information: NCT01690702.
MERiDiAN: A phase III, randomized, double-blind study of the efficacy, safety, and associated biomarkers of bevacizumab plus paclitaxel compared with paclitaxel plus placebo, as first-line treatment of patients with HER2-negative metastatic breast cancer.
Authors: Miles David , Faoro Leonardo , Wang Yan V. , O'Shaughnessy Joyce 
Published: March 2020

TPS1142^ Background: Bevacizumab (BV), a humanized monoclonal antibody targeting the angiogenic VEGF, has demonstrated activity in patients with metastatic breast cancer (MBC). Plasma VEGF-A levels ([VEGF-A]p) appear to positively correlate with the effect of BV on progression-free survival (PFS) in MBC, metastatic pancreatic, and advanced gastric cancers. The MERiDiAN study will prospectively investigate (1) whether baseline [VEGF-A]ppredict treatment benefit with BV, (2) efficacy of BV with weekly paclitaxel (P), based on previously observed differences in the magnitude of benefit compared with BV + non-P chemotherapies. Methods: MERiDiAN is a global, randomized, double-blind, phase III study enrolling patients with HER2-negative MBC (first patient was enrolled in August 2012). The co-primary endpoints are PFS by investigator assessment in the intent-to-treat (ITT) population, and PFS in the subgroup with high baseline [VEGF-A]p. Secondary endpoints are overall survival (OS), 1-year survival, objective response rate and duration, and safety. Exploratory objectives include assessing the predictive or prognostic potential of blood, DNA and tumor tissue markers, and genetic variants involved in angiogenesis and tumorigenesis, with regard to BV efficacy and safety.Patients will be randomized 1:1 to either P 90 mg/m2 IV weekly (qw) for 3 weeks followed by a 1-week rest and BV 10 mg/kg every 2 weeks (q2w) until disease progression (PD); or P 90 mg/m2IV qw for 3 weeks followed by a 1-week rest and placebo 10 mg/kg q2w until PD. An interim analysis of OS will be performed at the time of the primary PFS analysis. Clinical Trial Registry Number NCT01663727. Clinical trial information: NCT01663727.
Randomized, placebo controlled, phase III trial of low-dose tamoxifen in women with intraepithelial neoplasia.
Authors: Puntoni Matteo , Bonanni Bernardo , D'Aiuto Giuseppe , Ponti Antonio , Paquola Maria Grazia , Cortesi Laura , D'Amico Cosimo , Gulisano Marcella , Cruciani Giorgio , Falcini Fabio , Giardina Giovanni , Cagossi Katia , Regolo Lea , Renne Mariuccia , Canavese Giuseppe , Branchi Daniela , Marra Domenico , Guerrieri-Gonzaga Aliana , Johansson Harriet Ann , De Censi Andrea 
Published: March 2020

TPS1610 Background: Breast IntraEpithelial Neoplasia (IEN) is associated with a 8-10 fold increased risk of invasive disease, thus representing an important target for chemoprevention. The NSABP-P1 trial showed that tamoxifen (TAM) at 20 mg/day is associated with a 86% reduction of invasive breast cancer (BC) in women with previous atypical ductal hyperplasia (ADH) (RR=0.14, 95% IC, 0.03-0.47) and with a 56% risk reduction in women with previous LCIS (RR=0.44, 0.16-1.06). However, TAM broad use in chemoprevention has been significantly hampered by the increased risk of endometrial cancer and of venous thromboembolism (VTE). We recently showed that a dose of 5 mg/day does not increase endometrial proliferation, is associated with a decrease of the estrogenic activity of TAM on IGF-I, SHBG and antithrombin-III, and attains at the breast tissue level a concentration 10 times higher than that needed to inhibit cell growth in vitro. The CYP2D6 enzyme mediates oxidation of N-desmethyl tamoxifen to endoxifen, the most active metabolite of TAM. The SNP CYP2D6*4 (1846G>A) allele accounts for 75% of poor metabolizer phenotype which have been associated with a higher risk of a breast event compared to wildtype (Pharmacogenomics J. 2011;11:100-7). Methods: A randomized double-blind placebo-controlled phase III trial to assess the efficacy and safety of 5 mg/day TAM vs. placebo for 3 years in women with previous IEN (LIN 2-3 and ER+ or unknown DIN 1b-3). In Europe TAM is not registered in women with prior DCIS. 1400 women are needed to detect 50% reduction in the incidence of BC in the TAM arm (80% power, 1-sided 5% α error). Secondary endpoints are: incidence of other non-invasive breast disorders, endometrial cancer, clinical bone fractures, cardiovascular events, VTE events, and clinically manifest cataract. Pharmacogenetic endpoints includes the association between CYP2D6 genotype and modulation of biomarkers of TAM efficacy and safety (circulating IGF-I, hormones, mammographic density, endometrial thickness and hot flashes) and clinical events. As of February 5, 2013, 18 enrolment centers have been activated and n=338 women have been randomized. No suspected unexpected serious adverse reactions were registered. Clinical trial information: NCT01357772.