Menée à l'aide de cultures tridimensionnelles de cellules de cancer du sein, cette étude montre que le facteur nucléaire NF-κB régule la radiorésistance des cellules tumorales induite par l'intégrine

NF-κB regulates radioresistance mediated by β1-integrin in three-dimensional culture of breast cancer cells

Ahmed, Kazi Mokim ; Zhang, Hui ; Park, Catherine C

β1-integrin induction enhances breast cancer cell survival after exposure to ionizing radiation (IR), but the mechanisms of this effect remain unclear. Although NF-κB initiates prosurvival signaling pathways post-IR, the molecular function of NF-κB with other key elements in radioresistance, particularly with respect to extracellular matrix-induced signaling, is not known. We discovered a typical NF-κB binding site in the β1-integrin promoter region, indicating a possible regulatory role for [...]

Menée à l'aide de lignées cellulaires de carcinome rhinopharyngé et à l'aide d'échantillons tumoraux, cette étude montre que le microARN-324-3p, en agissant sur l'expression de WNT2B, régule la radiorésistance des cellules tumorales

MicroRNA-324-3p regulates nasopharyngeal carcinoma radioresistance by directly targeting WNT2B

Li, Guo ; Liu, Yong ; Su, Zhongwu ; Ren, Shuling ; Zhu, Gangcai ; Tian, Yongquan ; Qiu, Yuanzheng

AbstractPurpose Radioresistance severely restricts the clinical treatment of nasopharyngeal carcinoma (NPC). Accumulating evidence demonstrates that aberrant expression of microRNAs (miRNAs) contributes to cancer progression and sensitivity to radiation. Therefore, we aimed to identify miRNAs associated with radioresistance in NPC. Methods Aberrant miRNA-324-3p expression in NPC CNE-2 cells with radioresistance (CNE-2-Rs), compared to its parental cells, was screened by high-throughput [...]

Menée sur 26 patients pédiatriques atteints d'un chordome ou d'un chondrosarcome traité entre 2000 et 2010, cette étude évalue, du point de vue du contrôle local de la maladie et de la survie globale à 5 ans, l'efficacité d'une protonthérapie avec système de balayage du faisceau de protons

Spot-Scanning Proton Radiation Therapy for Pediatric Chordoma and Chondrosarcoma: Clinical Outcome of 26 Patients Treated at Paul Scherrer Institute

Rombi, Barbara ; Ares, Carmen ; Hug, Eugen B. ; Schneider, Ralf ; Goitein, Gudrun ; Staab, Adrian ; Albertini, Francesca ; Bolsi, Alessandra ; Lomax, Antony J. ; Timmermann, Beate

To evaluate the clinical results of fractionated spot-scanning proton radiation therapy (PT) in 26 pediatric patients treated at Paul Scherrer Institute for chordoma (CH) or chondrosarcoma (CS) of the skull base or axial skeleton. Between June 2000 and June 2010, 19 CH and 7 CS patients with tumors originating from the skull base (17) and the axial skeleton (9) were treated with PT. Mean age at the time of PT was 13.2 years. The mean prescribed dose was 74 Gy (relative biological effectiveness [...]

A partir des données du registre américain SEER portant sur 1 458 patients atteints d'un cancer de l'œsophage de stade T1N0M0, cette étude analyse sur la période 1998-2008 l'évolution de l'utilisation de différentes modalités de traitement localisé et évalue leur efficacité du point de vue de la survie spécifique et de la survie globale à 5 ans

Treatment Modalities for T1N0 Esophageal Cancers: A Comparative Analysis of Local Therapy Versus Surgical Resection

Berry, Mark F. ; Zeyer-Brunner, Josiane ; Castleberry, Anthony W. ; Martin, Jeremiah T. ; Gloor, Beat ; Pietrobon, Ricardo ; D’Amico, Thomas A. ; Worni, Mathias

Background: To investigate the role of nonsurgical treatment for early-stage esophageal cancer, we compared the outcomes of local therapy to esophagectomy, using a large, national database. Methods: Five-year cancer-specific and overall survival (OS) of patients, with T1N0M0 squamous cell or adenocarcinoma of the mid or distal esophagus treated with either surgery or local therapy, with ablative and/or excision techniques, in the Surveillance Epidemiology and End Results cancer registry from [...]

Menée sur 147 patients atteints d'une ou plusieurs tumeurs rénales traitées entre 2007 et 2012, cette étude prospective évalue l'efficacité d'une cryoablation percutanée guidée par l'image et le taux de complications associées

Percutaneous cryoablation of renal tumours: outcomes from 171 tumours in 147 patients

Breen, David J. ; Bryant, Timothy J. ; Abbas, Ausami ; Shepherd, Beth ; McGill, Neil ; Anderson, Jane A. ; Lockyer, Richard C. ; Hayes, Matthew C. ; George, Steve L.

Objective * To evaluate the technical and oncological efficacy of an image-guided cryoablation programme for renal tumours. Patients and Methods * A prospective analysis of technical and radiological outcomes was undertaken after treatment of 171 consecutive tumours in 147 patients. * Oncological efficacy in a subset of 125 tumours in 104 patients with >6 months' radiological follow-up and a further subset of 62 patients with solitary, biopsy-proven renal carcinoma was also analysed. * Factors [...]

Menée sur 777 patients présentant des métastases cérébrales, cette étude rétrospective française évalue, du point de vue de la survie et en fonction de la pathologie, l'efficacité d'une radiothérapie du cerveau entier précédée ou non par une intervention chirurgicale et identifie les facteurs pronostiques associés

Institutional, Retrospective Analysis of 777 Patients With Brain Metastases: Treatment Outcomes and Diagnosis-Specific Prognostic Factors

Antoni, Delphine ; Clavier, Jean-Baptiste ; Pop, Marius ; Schumacher, Catherine ; Lefebvre, François ; Noël, Georges

To retrospectively evaluate the prognostic factors and survival of a series of 777 patients with brain metastases (BM) from a single institution. Patients were treated with surgery followed by whole-brain radiation therapy (WBRT) or with WBRT alone in 16.3% and 83.7% of the cases, respectively. The patients were RPA (recursive partitioning analysis) class I, II, and III in 11.2%, 69.6%, and 18.4% of the cases, respectively; RPA class II-a, II-b, and II-c in 8.3%, 24.8%, and 66.9% of the cases, [...]

Cette étude met en évidence l'intérêt d'un modèle murin de tératome dérivé de cellules souches embryonnaires humaines pour évaluer des traitements ciblant des marqueurs vasculaires tumoraux ou analyser des mécanismes biologiques liés aux cellules souches cancéreuses

A novel model for evaluating therapies targeting human tumor vasculature and human cancer stem-like cells

Burgos-Ojeda, Daniela ; McLean, Karen ; Bai, Shoumei ; Pulaski, Heather ; Gong, Yu-Song ; Silva, Ines ; Skorecki, Karl ; Tzukerman, Maty ; Buckanovich, Ronald J

Human tumor vessels express tumor vascular markers (TVMs), proteins that are not expressed in normal blood vessels. Antibodies targeting TVMs could act as potent therapeutics. Unfortunately, preclinical in vivo studies testing anti-human TVM therapies have been difficult to perform due to a lack of in vivo models with confirmed expression of human TVMs. We therefore evaluated TVM expression in a human embryonic stem cell derived teratoma (hESCT) tumor model previously shown to have human [...]

Menée sur des lignées cellulaires de leucémie myéloïde chronique à l'aide d'inhibiteurs de tyrosine kinase (imatinib, nilotinib, dasatinib, ponatinib et DCC-2036), cette étude évalue divers paramètres intracellulaires associés à la capacité de ces inhibiteurs à induire une apoptose

Threshold levels of ABL tyrosine kinase inhibitors retained in chronic myeloid leukemia cells define commitment to apoptosis

O'Hare, Thomas ; Eide, Christopher A. ; Agarwal, Anupriya ; Adrian, Lauren T. ; Zabriskie, Matthew S. ; MacKenzie, Ryan J. ; LaTocha, Dorian H. ; Johnson, Kara J. ; You, Huihong ; Luo, Jenny ; Riddle, Steven M. ; Marks, Bryan D. ; Vogel, Kurt W. ; Koop, Dennis R. ; Apgar, John ; Tyner, Jeffrey W. ; Deininger, Michael W ; Druker, Brian J

The imatinib paradigm in chronic myeloid leukemia (CML) established continuous BCR-ABL inhibition as a design principle for ABL tyrosine kinase inhibitors (TKIs). However, clinical responses seen in patients treated with the ABL TKI dasatinib despite its much shorter plasma half-life and the apparent rapid restoration of BCR-ABL signaling activity following once-daily dosing suggested acute, potent inhibition of kinase activity may be sufficient to irrevocably commit CML cells to apoptosis. To [...]

Menée sur des séries d'échantillons tumoraux prélevés au cours d'un traitement au vemurafenib sur 132 patients atteints d'un mélanome métastatique, cette étude met en évidence des mécanismes de signalisation MAPK associés à la résistance thérapeutique

Pharmacodynamic Effects and Mechanisms of Resistance to Vemurafenib in Patients With Metastatic Melanoma

Trunzer, Kerstin ; Pavlick, Anna C. ; Schuchter, Lynn ; Gonzalez, Rene ; McArthur, Grant A. ; Hutson, Thomas E. ; Moschos, Stergios J. ; Flaherty, Keith T. ; Kim, Kevin B. ; Weber, Jeffrey S. ; Hersey, Peter ; Long, Georgina V. ; Lawrence, Donald ; Ott, Patrick A. ; Amaravadi, Ravi K. ; Lewis, Karl D. ; Puzanov, Igor ; Lo, Roger S. ; Koehler, Astrid ; Kockx, Mark ; Spleiss, Olivia ; Schell-Steven, Annette ; Gilbert, Houston N. ; Cockey, Louise ; Bollag, Gideon ; Lee, Richard J. ; Joe, Andrew K. ; Sosman, Jeffrey A. ; Ribas, Antoni

Purpose To assess pharmacodynamic effects and intrinsic and acquired resistance mechanisms of the BRAF inhibitor vemurafenib in BRAFV600-mutant melanoma, leading to an understanding of the mechanism of action of vemurafenib and ultimately to optimization of metastatic melanoma therapy. Methods In the phase II clinical study NP22657 (BRIM-2), patients received oral doses of vemurafenib (960 mg twice per day). Serial biopsies were collected to study changes in mitogen-activated protein kinase [...]

Menée in vitro et à l'aide de xénogreffes de myélome multiple, cette étude évalue l'activité antitumorale d'un nouveau promédicament du melphalan, le Mel-flufen

In vitro and In vivo Antitumor Activity of a Novel Alkylating Agent Melphalan-flufenamide Against Multiple Myeloma Cells

Chauhan, Dharminder ; Ray, Arghya ; Viktorsson, Kristina ; Spira, Jack ; Paba-Prada, Claudia ; Munshi, Nikhil C. ; Richardson, Paul G. ; Lewensohn, Rolf ; Anderson, Kenneth C.

Purpose: The alkylating agent melphalan prolongs survival in multiple myeloma (MM) patients; however, it is associated with toxicities and development of drug-resistance. Here, we evaluated the efficacy of melphalan-flufenamide (Mel-flufen), a novel dipeptide prodrug of melphalan in MM. Experimental Design: MM cell lines, primary patient cells, and the human MM xenograft animal model were utilized to study the antitumor activity of mel-flufen. Results: Low doses of mel-flufen triggers a more [...]

Menée à l'aide de deux modèles orthotopiques de cancer de l'ovaire, cette étude met en évidence des mécanismes par lesquels, via la régulation de la signalisation MAPK, des nanoparticules d'or inhibent la croissance tumorale et le processus métastatique

Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle

Arvizo, Rochelle R. ; Saha, Sounik ; Wang, Enfeng ; Robertson, J. David ; Bhattacharya, Resham ; Mukherjee, Priyabrata

Although biomedical applications of nanotechnology, which typically involve functionalized nanoparticles, have taken significant strides, biological characterization of unmodified nanoparticles remains underinvestigated. Herein we demonstrate that unmodified gold nanoparticles (AuNPs) inhibit the proliferation of cancer cells in a size- and concentration-dependent manner by abrogating MAPK-signaling. In addition, these AuNPs reverse epithelial-mesenchymal transition (EMT) in cancer cells by [...]

Cet article passe en revue les perspectives offertes par des stratégies d'immunothérapie active pour le traitement d'un cancer du sein HER2+

Active immunotherapy in HER2 overexpressing breast cancer: current status and future perspectives

Milani, A. ; Sangiolo, D. ; Montemurro, F. ; Aglietta, M. ; Valabrega, G.

Background The use of anti-HER2 monoclonal antibodies (mAbs) has improved the clinical outcome of HER2-overexpressing breast cancers (BCs). Unfortunately, often these tumors tend to relapse and, when metastatic, the duration of clinical benefit is limited over time and almost invariably followed by tumor progression. Alternative approaches to this essentially passive immunotherapy are therefore needed in HER2-overexpressing BC patients. As HER2 is one of the most suitable targets for active [...]

Mené sur 101 patients atteints d'un carcinome hépatocellulaire de stade avancé, cet essai de phase II évalue, du point de vue de la survie sans progression, le sorafenib à haute dose après l'observation radiologique de la progression de la maladie

A Phase II Randomized Dose Escalation Trial of Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Rimassa, Lorenza ; Pressiani, Tiziana ; Boni, Corrado ; Carnaghi, Carlo ; Rota Caremoli, Elena ; Fagiuoli, Stefano ; Foa, Paolo ; Salvagni, Stefania ; Cortesi, Enrico ; Chiara Tronconi, Maria ; Personeni, Nicola ; Bozzarelli, Silvia ; Chiara Banzi, Maria ; Fanello, Silvia ; Romano Lutman, Fabio ; Giordano, Laura ; Santoro, Armando

Background. Sorafenib has proven survival benefits in patients with advanced hepatocellular carcinoma (HCC). The viability of continuing sorafenib at a higher dosage in patients who experienced radiologic disease progression was investigated. Methods. Patients who experienced disease progression while on sorafenib 400 mg twice daily were randomized to sorafenib 600 mg twice daily (n = 49) or best supportive care (n = 52). The primary end point was progression-free survival (PFS). Time to [...]

Menée sur 207 patients d'âge supérieur à 65 ans et atteints d'un cancer métastatique du côlon-rectum ou du poumon non à petites cellules, cette étude évalue les toxicités cardiaques associées au bevacizumab en combinaison avec une chimiothérapie

Toxicity of Bevacizumab in Combination with Chemotherapy in Older Patients

Mohile, Supriya G. ; Hardt, Molly ; Tew, William ; Owusu, Cynthia ; Klepin, Heidi ; Gross, Cary ; Gajra, Ajeet ; Lichtman, Stuart M. ; Feng, Tao ; Togawa, Kayo ; Ramani, Rupal ; Katheria, Vani ; Hansen, Kurt ; Hurria, Arti

Background. Bevacizumab leads to improved survival for patients with metastatic colorectal cancer (CRC) or non-small cell lung cancer (NSCLC) when added to chemotherapy. Little is known about factors associated with receipt of bevacizumab, or whether bevacizamab is associated with increased toxicity when added to chemotherapy. Patients and Methods. We conducted a prospective study of patients aged ≥65 years, which evaluated the association between geriatric assessment (GA) metrics and [...]

Mené sur 94 patients atteints d'une tumeur solide réfractaire aux traitements de référence, cet essai de phase I évalue la dose maximale tolérée et la toxicité d'un composé appelé IPI-926, un inhibiteur de la voie de signalisation Hedgehog

Phase 1 Study of the Hedgehog Pathway Inhibitor IPI-926 in Adult Patients with Solid Tumors

Jimeno, Antonio ; Weiss, Glen J. ; Miller, Wilson H ; Gettinger, Scott N ; Eigl, Bernhard ; Chang, Anne Lynne S ; Dunbar, Joi ; Devens, Shannon ; Faia, Kerrie ; Skliris, Georgio ; Kutok, Jeffery L. ; Lewis, Karl D ; Tibes, Raoul ; Sharfman, William H ; Ross, Robert W ; Rudin, Charles M

Purpose: To conduct a first-in-human Phase 1 study to determine the dose limiting toxicities (DLTs), characterize the pharmacokinetic profile, and document the antitumor activity of IPI-926, a new chemical entity that inhibits the Hedgehog pathway (HhP). Methods: Patients with solid tumors refractory to standard therapy were given IPI-926 once daily (QD) by mouth in 28-day cycles. The starting dose was 20 mg and an accelerated titration schedule was used until standard 3+3 dose escalation [...]

A partir d'une revue de la littérature (30 articles identifiés), cette étude évalue les toxicités cardiovasculaires associées à un traitement comprenant du 5-fluorouracil ou de la capécitabine

Cardiotoxicity in cancer patients treated with 5-fluorouracil or capecitabine: A systematic review of incidence, manifestations and predisposing factors

Polk, Anne ; Vaage-Nilsen, Merete ; Vistisen, Kirsten ; Nielsen, Dorte L.

Purpose : To systematically review the incidence, manifestations and predisposing factors for cardiovascular toxicity in cancer patients treated with systemic 5-fluorouracil or capecitabine. Design : We searched PubMed, EMBASE and Web of science for studies with 20 cancer patients evaluating cardiovascular toxicity of 5-fluorouracil and capecitabine. We hand searched the reference lists of all included studies. Study selection and assessment of risk of bias were performed by two authors [...]

Mené sur 51 patients atteints d'un lymphome primitif du médiastin, cet essai de phase II évalue un traitement combinant le rituximab, une chimiothérapie EPOCH (étoposide, doxorubicine, cyclophosmamide, vincristine) avec une pharmacocinétique optimisée et du filgastrim, sans radiothérapie

Dose-Adjusted EPOCH-Rituximab Therapy in Primary Mediastinal B-Cell Lymphoma

Dunleavy, Kieron ; Pittaluga, Stefania ; Maeda, Lauren S. ; Advani, Ranjana ; Chen, Clara C. ; Hessler, Julie ; Steinberg, Seth M. ; Grant, Cliona ; Wright, George ; Varma, Gaurav ; Staudt, Louis M. ; Jaffe, Elaine S. ; Wilson, Wyndham H.

Background : Primary mediastinal B-cell lymphoma is a distinct subtype of diffuse large-B-cell lymphoma that is closely related to nodular sclerosing Hodgkin's lymphoma. Patients are usually young and present with large mediastinal masses. There is no standard treatment, but the inadequacy of immunochemotherapy alone has resulted in routine consolidation with mediastinal radiotherapy, which has potentially serious late effects. We aimed to develop a strategy that improves the rate of cure and [...]

Menée sur une série de 160 patients atteints d'un mélanome métastatique, cette étude rétrospective évalue, du point de vue de la survie sans progression, l'effet de thérapies ciblées en fonction de la présence de mutations somatiques, notamment du gène BRAF

Melanoma patients in a phase I clinic: molecular aberrations, targeted therapy and outcomes

Henary, H. ; Hong, D. S. ; Falchook, G. S. ; Tsimberidou, A. ; George, G.C. ; Wen, S. ; Wheler, J. ; Fu, S. ; Naing, A. ; Piha-Paul, S. ; Janku, F. ; Kim, K. B. ; Hwu, P. ; Kurzrock, R.

Background The purpose of the study was to assess the outcome of patients with advanced melanoma treated with matched molecularly targeted therapy. Patients and methods We reviewed 160 consecutive patients with metastatic melanoma treated in the phase I program (N = 35 protocols). Treatment was considered to be ‘matched’ (N = 84) if at least one drug in the regimen was known to inhibit the functional activity of at least one of the patient's mutations. Results Of 160 patients, 134 (83.7%) had [...]

Menée sur 38 patients atteints d'un cancer métastatique de la prostate résistant à la castration (âge médian : 71 ans), cette étude évalue l'activité antitumorale de l'abiratérone et de la prednisolone après un traitement à base de docétaxel et d'enzulatamide

Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100)

Loriot, Y. ; Bianchini, D. ; Ileana, E. ; Sandhu, S. ; Patrikidou, A. ; Pezaro, C. ; Albiges, L. ; Attard, G. ; Fizazi, K. ; De Bono, J.S. ; Massard, C.

Background Androgen receptor (AR) signalling remains critically important in metastatic castration-resistant prostate cancer (mCRPC) as confirmed by recent phase III trials, showing a survival advantage for abiraterone acetate and enzalutamide (MDV3100). The antitumour activity of abiraterone and prednisolone in patients pre-treated with enzalutamide is as yet unknown. Patients and methods We investigated the antitumour activity of abiraterone and prednisolone in patients with mCRPC who had [...]

Mené sur 138 patients présentant des métastases hépatiques non résécables d'un cancer colorectal sans mutation du gène KRAS, cet essai de phase II évalue l'efficacité du cetuximab, en combinaison avec une chimiothérapie FOLFIRI ou mFOLFOX6, pour améliorer la résécabilité des métastases hépatiques

Randomized Controlled Trial of Cetuximab Plus Chemotherapy for Patients With KRAS Wild-Type Unresectable Colorectal Liver-Limited Metastases

Ye, Le-Chi ; Liu, Tian-Shu ; Ren, Li ; Wei, Ye ; Zhu, De-Xiang ; Zai, Sheng-Yong ; Ye, Qing-Hai ; Yu, Yiyi ; Xu, Bo ; Qin, Xin-Yu ; Xu, Jianmin

Purpose To assess the effects of cetuximab plus chemotherapy as first-line treatment for unresectable colorectal liver metastases (CLMs). Patients and Methods After resection of their primary tumors, patients with KRAS wild-type synchronous nonresectable liver-limited metastases from colorectal cancer were randomly assigned to receive chemotherapy (FOLFIRI [fluorouracil, leucovorin, and irinotecan] or mFOLFOX6 [modified fluorouracil, leucovorin, and oxaliplatin]) plus cetuximab (arm A) or [...]

Mené sur 40 patients atteints d'un cancer colorectal métastatique réfractaire, cet essai de phase II évalue, du point de vue de la survie sans progression à 2 mois, un traitement combinant tivozanib et everolimus

Multicenter Phase II Study of Tivozanib (AV-951) and Everolimus (RAD001) for Patients With Refractory, Metastatic Colorectal Cancer

Wolpin, Brian M. ; Ng, Kimmie ; Zhu, Andrew X. ; Abrams, Thomas ; Enzinger, Peter C. ; McCleary, Nadine J. ; Schrag, Deborah ; Kwak, Eunice L. ; Allen, Jill N. ; Bhargava, Pankaj ; Chan, Jennifer A. ; Goessling, Wolfram ; Blaszkowsky, Lawrence S. ; Supko, Jeffrey G. ; Elliot, Meaghan ; Sato, Kaori ; Regan, Eileen ; Meyerhardt, Jeffrey A. ; Fuchs, Charles S.

Background. Treatments that target the vascular endothelial growth factor (VEGF) pathway have efficacy in colorectal cancer. We evaluated tolerability and efficacy of tivozanib (an oral VEGF receptor-1, -2, -3 inhibitor) plus everolimus (an oral mammalian target of rapamycin inhibitor). Methods. The phase Ib study followed a 3 + 3 dose-escalation design with three dose levels. The primary objective in the follow-on phase II study was improvement in 2-month progression-free survival (PFS) from [...]

Mené sur 30 patients atteints d'un liposarcome de stade avancé présentant une amplification du gène CDK4, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression à 12 semaines, et la toxicité d'un composé appelé PD0332991, un inhibiteur de CDK4

Phase II Trial of the CDK4 Inhibitor PD0332991 in Patients With Advanced CDK4-Amplified Well-Differentiated or Dedifferentiated Liposarcoma

Dickson, Mark A. ; Tap, William D. ; Keohan, Mary Louise ; D'Angelo, Sandra P. ; Gounder, Mrinal M. ; Antonescu, Cristina R. ; Landa, Jonathan ; Qin, Li-Xuan ; Rathbone, Dustin D. ; Condy, Mercedes M. ; Ustoyev, Yelena ; Crago, Aimee M. ; Singer, Samuel ; Schwartz, Gary K.

Purpose CDK4 is amplified in > 90% of well-differentiated (WDLS) and dedifferentiated liposarcomas (DDLS). The selective cyclin-dependent kinase 4 (CDK4)/CDK6 inhibitor PD0332991 inhibits growth and induces senescence in cell lines and xenografts. In a phase I trial of PD0332991, several patients with WDLS or DDLS experienced prolonged stable disease. We performed an open-label phase II study to determine the safety and efficacy of PD0332991 in patients with advanced WDLS/DDLS. Patients and [...]

Mené sur 424 patientes atteintes d'un cancer du sein HER2+ métastatique ou localement récidivant, cet essai de phase III évalue, du point de vue de la survie sans progression, l'ajout de bevacizumab à un traitement de première ligne combinant docétaxel et trastuzumab

AVEREL: A Randomized Phase III Trial Evaluating Bevacizumab in Combination With Docetaxel and Trastuzumab as First-Line Therapy for HER2-Positive Locally Recurrent/Metastatic Breast Cancer

Gianni, Luca ; Romieu, Gilles H. ; Lichinitser, Michail ; Serrano, Sergio V. ; Mansutti, Mauro ; Pivot, Xavier ; Mariani, Paola ; Andre, Fabrice ; Chan, Arlene ; Lipatov, Oleg ; Chan, Stephen ; Wardley, Andrew ; Greil, Richard ; Moore, Nicola ; Prot, Sylvie ; Pallaud, Celine ; Semiglazov, Vladimir

Purpose The AVEREL trial [A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With HER2-Positive Metastatic Breast Cancer] evaluated first-line bevacizumab-containing therapy for human epidermal growth factor receptor 2 (HER2) –positive locally recurrent/metastatic breast cancer (LR/MBC). Patients and Methods Patients with measurable/evaluable HER2-positive LR/MBC who had not received trastuzumab or chemotherapy for LR/MBC were stratified by prior [...]

Cet article fait le point sur les avancées récentes en matière de prévention et de prise en charge de l'adénocarcinome de l'œsophage

Recent developments in esophageal adenocarcinoma

Lagergren, Jesper ; Lagergren, Pernilla

Esophageal adenocarcinoma (EAC) is characterized by 6 striking features: increasing incidence, male predominance, lack of preventive measures, opportunities for early detection, demanding surgical therapy and care, and poor prognosis. Reasons for its rapidly increasing incidence include the rising prevalence of gastroesophageal reflux and obesity, combined with the decreasing prevalence of Helicobacter pylori infection. The strong male predominance remains unexplained, but hormonal influence [...]

Menée sur 429 patientes atteintes d'un cancer primitif du sein HER2+, cet essai de phase III identifie les facteurs clinico-pathologiques associés à une mastectomie ou à une chirurgie mammaire conservatrice après un traitement néoadjuvant combinant trastuzumab et/ou lapatinib avec paclitaxel

Factors associated with surgical management following neoadjuvant therapy in patients with primary HER2-positive breast cancer: results from the NeoALTTO phase III trial

Criscitiello, C. ; Azim, H. A. ; Agbor-tarh, D. ; de Azambuja, E. ; Piccart, M. ; Baselga, J. ; Eidtmann, H. ; Di Cosimo, S. ; Bradbury, I. ; Rubio, I. T.

Background The NeoALTTO trial showed that dual HER2 blockade nearly doubles the rate of pathologic complete response (pCR) in patients with primary HER2-positive breast cancer. However, this did not translate into a higher rate of breast-conserving surgery (BCS).Patients and methods In NeoALTTO, patients with HER2-positive breast cancer were randomly assigned to either trastuzumab, lapatinib or their combination with paclitaxel before surgery with pCR as the primary end point. We investigated [...]

Menée à partir de données portant sur 163 patientes atteintes d'un cancer localement avancé du col de l'utérus (durée médiane de suivi : 36 mois), cette étude évalue, par rapport à une hystérectomie radicale et du point de vue du taux de contrôle locorégional, du taux de survie globale à 3 ans et de la toxicité, l'intérêt d'une curiethérapie adaptative guidée par l'imagerie 3D après une chimioradiothérapie concomitante

Adaptive 3D Image-Guided Brachytherapy: A Strong Argument in the Debate on Systematic Radical Hysterectomy for Locally Advanced Cervical Cancer

Mazeron, Renaud ; Gilmore, Jennifer ; Dumas, Isabelle ; Champoudry, Jérôme ; Goulart, Jennifer ; Vanneste, Ben ; Tailleur, Anne ; Morice, Philippe ; Haie-Meder, Christine

Purpose. To evaluate the outcomes of patients with locally advanced cervical cancer treated with three-dimensional image-guided brachytherapy (IGABT) after concomitant chemoradiation (CCRT).Material and Methods. Data from patients treated with CCRT followed by magnetic resonance imaging-guided or computed tomography-guided pulsed-dose-rate brachytherapy, performed according to the Groupe Européen de Curiethérapie–European Society for Radiotherapy and Oncology guidelines, were reviewed. At [...]

Cet article analyse les biais d'interprétation des résultats d'essais cliniques de phase III intégrant l'évaluation d'un traitement anticancéreux et d'un biomarqueur

Phase III Clinical Trials That Integrate Treatment and Biomarker Evaluation

Freidlin, Boris ; Sun, Zhuoxin ; Gray, Robert ; Korn, Edward L.

Many new anticancer agents are molecularly targeted and thereforemayonly benefit a subgroup of a histologically defined population. Development of these agents relies on biomarkers that identify a sensitive subpopulation (ie, the assumption is made that a binary biomarker can classify patients into two subgroups so that the agent works in one subgroup but not in the other)...