Menée à partir d'une revue systématique de la littérature publiée jusqu'en janvier 2015 (8 essais, 2 515 patients atteints d'un carcinome gastrique non métastatique), cette méta-analyse évalue le bénéfice, en termes de survie, d'une lymphadénectomie en fonction de son étendue (D1, D2 ou D3)

Lymphadenectomy extent and survival of patients with gastric carcinoma: a systematic review and meta-analysis of time-to-event data from randomized trials

Mocellin, Simone ; Nitti, Donato

Background : The extent of lymph node dissection in patients with resectable non-metastatic primary carcinoma of the stomach is still a controversial matter of debate, with special regard to its effect on survival. Materials and methods : We conducted a systematic review and meta-analysis of time-to-event data from randomized controlled trials (RCTs) comparing the three main types of lymphadenectomy (D1, D2, and D3) for gastric cancer. Hazard ratio (HR) was considered the effect measure for [...]

Mené sur 438 patients atteints d'un cancer de la prostate, cet essai randomisé évalue, du point de vue du taux de marges de résection positives et en fonction du stade de la maladie au diagnostic, l'intérêt d'une IRM avant une prostatectomie radicale laparoscopique assistée par robot

Does Preoperative Magnetic Resonance Imaging Reduce the Rate of Positive Surgical Margins at Radical Prostatectomy in a Randomised Clinical Trial?

Rud, Erik ; Baco, Eduard ; Klotz, Dagmar ; Rennesund, Kristin ; Svindland, Aud ; Berge, Viktor ; Lundeby, Eskild ; Wessel, Nicolai ; Hoff, Jon-Roar ; Berg, Rolf Eigil ; Diep, Lien ; Eggesbø, Heidi B. ; Eri, Lars Magne

Background : Magnetic resonance imaging (MRI) has the potential to help the surgeon tailor radical prostatectomy (RP) more accurately according to the location and extent of the tumour and thereby reduce the rate of positive surgical margins (PSMs). Objective : To evaluate the benefit of performing MRI prior to RP. Design, setting, and participants : This single-institution randomised trial included 438 patients between December 2009 and June 2012 who were scheduled for robot-assisted [...]

Menée à partir des données des registres américains des cancers portant sur 31 137 patients atteints d'un cancer localisé de la prostate diagnostiqué entre 1992 et 2009 (âge 65 ans ou plus), cette étude analyse l'utilisation de traitements conservateurs (radiothérapie, cryothérapie, traitement anti-androgénique), puis estime la mortalité spécifique et la mortalité globale à 15 ans en fonction du score de Gleason

Fifteen-year Outcomes Following Conservative Management Among Men Aged 65 Years or Older with Localized Prostate Cancer

Lu-Yao, Grace L. ; Albertsen, Peter C. ; Moore, Dirk F. ; Lin, Yong ; DiPaola, Robert S. ; Yao, Siu-Long

Background : To understand the threat posed by localized prostate cancer and the potential impact of surgery or radiation, patients and healthcare providers require information on long-term outcomes following conservative management. Objective : To describe 15-yr survival outcomes and cancer therapy utilization among men 65 years and older managed conservatively for newly diagnosed localized prostate cancer. Design, settings, and participants : This is a population-based cohort study with [...]

Menée sur des lignées cellulaires, cette étude met en évidence des mécanismes par lesquels, en restaurant la recombinaison homologue, la protéine REV7 (aussi appelée MAD2L2) favorise la résistance à un traitement à base d'inhibiteur de PARP

REV7 counteracts DNA double-strand break resection and affects PARP inhibition

Xu, Guotai ; Chapman, J. Ross ; Brandsma, Inger ; Yuan, Jingsong ; Mistrik, Martin ; Bouwman, Peter ; Bartkova, Jirina ; Gogola, Ewa ; Warmerdam, Daniel ; Barazas, Marco ; Jaspers, Janneke E. ; Watanabe, Kenji ; Pieterse, Mark ; Kersbergen, Ariena ; Sol, Wendy ; Celie, Patrick H. N. ; Schouten, Philip C. ; van den Broek, Bram ; Salman, Ahmed ; Nieuwland, Marja ; de Rink, Iris ; de Ronde, Jorma ; Jalink, Kees ; Boulton, Simon J. ; Chen, Junjie ; van Gent, Dik C. ; Bartek, Jiri ; Jonkers, Jos ; Borst, Piet ; Rottenberg, Sven

Error-free repair of DNA double-strand breaks (DSBs) is achieved by homologous recombination (HR), and BRCA1 is an important factor for this repair pathway. In the absence of BRCA1-mediated HR, the administration of PARP inhibitors induces synthetic lethality of tumour cells of patients with breast or ovarian cancers. Despite the benefit of this tailored therapy, drug resistance can occur by HR restoration. Genetic reversion of BRCA1-inactivating mutations can be the underlying mechanism of [...]

Cet article passe en revue les perspectives offertes par les travaux récents sur les récepteurs hépatiques X pour développer de nouveaux traitements anticancéreux

Targeting liver X receptors in cancer therapeutics

Lin, Chin-Yo ; Gustafsson, Jan-Åke

Members of the nuclear receptor superfamily of ligand-dependent transcription factors carry out vital cellular functions and are highly druggable therapeutic targets. Liver X receptors (LXRs) are nuclear receptor family members that function in cholesterol transport, glucose metabolism and the modulation of inflammatory responses. There is now accumulating evidence to support the involvement of LXRs in a variety of malignancies and the potential efficacy of their ligands in these diseases. This [...]

Cet article passe en revue les travaux récents ayant identifié des facteurs permettant de rendre compte d'une biodisponibilité variable des inhibiteurs de tyrosine kinase administrés par voie orale pour le traitement des cancers

Variability in bioavailability of small molecular tyrosine kinase inhibitors

Herbrink, Maikel ; Nuijen, Bastiaan ; Schellens, Jan H. M. ; Beijnen, Jos H.

Small molecular Tyrosine Kinase Inhibitors (smTKIs) are in the centre of the very quickly expanding area of personalized chemotherapy and oral applicability thereof. The number of drugs in this class is rapidly growing, with twenty current approvals by both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA). The drugs are, however, generally characterized by a poor oral, and thus variable, bioavailability. This results in significant variation in plasma levels and [...]

Cet article passe en revue les perspectives offertes par diverses formes d'immunothérapies pour le traitement des cancers hématologiques

Haematological malignancies: at the forefront of immunotherapeutic innovation

Bachireddy, Pavan ; Burkhardt, Ute E. ; Rajasagi, Mohini ; Wu, Catherine J.

The recent successes of cancer immunotherapies have stimulated interest in the potential widespread application of these approaches; haematological malignancies have provided both initial proofs of concept and an informative testing ground for various immune-based therapeutics. The immune-cell origin of many of the blood malignancies provides a unique opportunity both to understand the mechanisms of cancer immune responsiveness and immune evasion, and to exploit these mechanisms for therapeutic [...]

Menée à l'aide de modèles murins, cette étude met en évidence des mécanismes par lesquels une immunothérapie anti PD-L1 prévient le développement d'une leucémie lymphocytaire chronique

PD-L1 Checkpoint Blockade Prevents Immune Dysfunction and Leukemia Development in a Mouse Model of Chronic Lymphocytic Leukemia

McClanahan, Fabienne ; Hanna, Bola ; Miller, Shaun ; Clear, Andrew James ; Lichter, Peter ; Gribben, John G. ; Seiffert, Martina

Blockade of the PD-1/PD-L1 immune checkpoint augments anti-tumor immunity and induces durable responses in patients with solid cancers, but data on clinical efficacy in leukemias is largely missing. Chronic lymphocytic leukemia (CLL) is associated with a tumor-supportive microenvironment and a dysfunctional immune system, as shown by "exhausted" T cells, defective immunological synapse formation, and immunosuppressive myeloid cells. These defects involve aberrant expression of PD-L1 and are [...]

Menée in vitro et in vivo, cette étude met en évidence l'intérêt de plusieurs inhibiteurs sélectifs de BCL-XL pour augmenter, sans induire de poussées de neutropénie observées avec le navitoclax, l'efficacité du docétaxel dans le traitement des tumeurs solides

Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy

Leverson, Joel D. ; Phillips, Darren C. ; Mitten, Michael J. ; Boghaert, Erwin R. ; Diaz, Dolores ; Tahir, Stephen K. ; Belmont, Lisa D. ; Nimmer, Paul ; Xiao, Yu ; Ma, Xiaoju Max ; Lowes, Kym N. ; Kovar, Peter ; Chen, Jun ; Jin, Sha ; Smith, Morey ; Xue, John ; Zhang, Haichao ; Oleksijew, Anatol ; Magoc, Terrance J. ; Vaidya, Kedar S. ; Albert, Daniel H. ; Tarrant, Jacqueline M. ; La, Nghi ; Wang, Le ; Tao, Zhi-Fu ; Wendt, Michael D. ; Sampath, Deepak ; Rosenberg, Saul H. ; Tse, Chris ; S. Huang, David C. ; Fairbrother, Wayne J. ; Elmore, Steven W. ; Souers, Andrew J.

The BCL-2/BCL-XL/BCL-W inhibitor ABT-263 (navitoclax) has shown promising clinical activity in lymphoid malignancies such as chronic lymphocytic leukemia. However, its efficacy in these settings is limited by thrombocytopenia caused by BCL-XL inhibition. This prompted the generation of the BCL-2–selective inhibitor venetoclax (ABT-199/GDC-0199), which demonstrates robust activity in these cancers but spares platelets. Navitoclax has also been shown to enhance the efficacy of docetaxel in [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes suggérant l'intérêt d'une stratégie visant à augmenter l'activité tyrosine kinase de Syk pour surmonter une résistance thérapeutique chez les patients atteints d'une leucémie lymphoblastique aiguë

Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia

Chen, Zhengshan ; Shojaee, Seyedmehdi ; Buchner, Maike ; Geng, Huimin ; Lee, Jae Woong ; Klemm, Lars ; Titz, Bjorn ; Graeber, Thomas G. ; Park, Eugene ; Tan, Ying Xim ; Satterthwaite, Anne ; Paietta, Elisabeth ; Hunger, Stephen P. ; Willman, Cheryl L. ; Melnick, Ari ; Loh, Mignon L. ; Jung, Jae U. ; Coligan, John E. ; Bolland, Silvia ; Mak, Tak W. ; Limnander, Andre ; Jumaa, Hassan ; Reth, Michael ; Weiss, Arthur ; Lowell, Clifford A. ; Müschen, Markus

B cells are selected for an intermediate level of B-cell antigen receptor (BCR) signalling strength: attenuation below minimum (for example, non-functional BCR) or hyperactivation above maximum (for example, self-reactive BCR) thresholds of signalling strength causes negative selection. In ~25% of cases, acute lymphoblastic leukaemia (ALL) cells carry the oncogenic BCR-ABL1 tyrosine kinase (Philadelphia chromosome positive), which mimics constitutively active pre-BCR signalling. Current [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, via des modifications du micro-environnement tumoral, une thérapie ciblée (inhibiteur de BRAF, ALK ou EGFR) favorise de façon paradoxale la prolifération et la dissémination de cellules cancéreuses résistantes au traitement

Therapy-induced tumour secretomes promote resistance and tumour progression

Obenauf, Anna C. ; Zou, Yilong ; Ji, Andrew L. ; Vanharanta, Sakari ; Shu, Weiping ; Shi, Hubing ; Kong, Xiangju ; Bosenberg, Marcus C. ; Wiesner, Thomas ; Rosen, Neal ; Lo, Roger S. ; Massagué, Joan

Drug resistance invariably limits the clinical efficacy of targeted therapy with kinase inhibitors against cancer. Here we show that targeted therapy with BRAF, ALK or EGFR kinase inhibitors induces a complex network of secreted signals in drug-stressed human and mouse melanoma and human lung adenocarcinoma cells. This therapy-induced secretome stimulates the outgrowth, dissemination and metastasis of drug-resistant cancer cell clones and supports the survival of drug-sensitive cancer cells, [...]

Menée à l'aide d'un modèle murin, cette étude suggère l'intérêt d'une triple combinaison, associant un inhibiteur de BRAF, un inhibiteur de MEK et un anti-PD1, pour le traitement des patients atteints d'un mélanome métastatique présentant la mutation V600E du gène BRAF

Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAFV600E melanoma

Hu-Lieskovan, Siwen ; Mok, Stephen ; Homet Moreno, Blanca ; Tsoi, Jennifer ; Robert, Lidia ; Goedert, Lucas ; Pinheiro, Elaine M. ; Koya, Richard C. ; Graeber, Thomas G. ; Comin-Anduix, Begona ; Ribas, Antoni

Combining immunotherapy and BRAF targeted therapy may result in improved antitumor activity with the high response rates of targeted therapy and the durability of responses with immunotherapy. However, the first clinical trial testing the combination of the BRAF inhibitor vemurafenib and the CTLA4 antibody ipilimumab was terminated early because of substantial liver toxicities. MEK [MAPK (mitogen-activated protein kinase) kinase] inhibitors can potentiate the MAPK inhibition in BRAF mutant [...]

Menée à l'aide de xénogreffes de mélanome, cette étude met en évidence des mécanismes par lesquels, dans le micro-environnement tumoral, des lymphocytes T modifiés pour sécréter un ligand du récepteur TLR5 sont susceptibles d'augmenter l'efficacité d'une immunothérapie adoptive

TLR5 ligand-secreting T cells reshape the tumor microenvironment and enhance antitumor activity

Geng, Degui ; Kaczanowska, Sabina ; Tsai, Alexnder ; Younger, Kenisha ; Ochoa, Augusto ; Rapoport, Aaron P ; Ostrand-Rosenberg, Suzanne ; Davila, Eduardo

The tumor microenvironment counters antitumor T cell responses in part by blunting their activation and infiltration. Ligands that engage Toll-like receptors (TLR) on T cells and antigen-presenting cells can act as potent immune adjuvants. In this study, we show how tumor-reactive T cells engineered to secrete bacterial flagellin, a TLR5 ligand (TLR5L), can engender a co-stimulatory signal that augments antitumor activity. Human T cells engineered to express TLR5L along with DMF5, a T cell [...]

Menée à l'aide de lignées cellulaires, de modèles murins et d'échantillons tumoraux prélevés sur des patients atteints d'un glioblastome multiforme, cette étude met en évidence le rôle joué par le métabolisme de la glutamine dans la résistance à un traitement par inhibiteur de mTOR

Compensatory glutamine metabolism promotes glioblastoma resistance to mTOR inhibitor treatment

Tanaka, Kazuhiro ; Sasayama, Takashi ; Irino, Yasuhiro ; Takata, Kumi ; Nagashima, Hiroaki ; Satoh, Naoko ; Kyotani, Katsusuke ; Mizowaki, Takashi ; Imahori, Taichiro ; Ejima, Yasuo ; Masui, Kenta ; Gini, Beatrice ; Yang, Huijun ; Hosoda, Kohkichi ; Sasaki, Ryohei ; Mischel, Paul S. ; Kohmura, Eiji

The mechanistic target of rapamycin (mTOR) is hyperactivated in many types of cancer, rendering it a compelling drug target; however, the impact of mTOR inhibition on metabolic reprogramming in cancer is incompletely understood. Here, by integrating metabolic and functional studies in glioblastoma multiforme (GBM) cell lines, preclinical models, and clinical samples, we demonstrate that the compensatory upregulation of glutamine metabolism promotes resistance to mTOR kinase inhibitors. [...]

Mené sur 51 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue la dose maximale tolérée du nintedanib et met en évidence ses effets à l'aide d'examens par IRM dynamique de contraste

Phase I Study of Nintedanib Incorporating Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Patients With Advanced Solid Tumors

Lee, Chooi Peng ; Taylor, N. Jane ; Attard, Gerhardt ; Pacey, Simon ; Nathan, Paul D. ; de Bono, Johann S. ; Temple, Graham ; Bell, Susan ; Stefanic, Martin ; Stopfer, Peter ; Tang, Adrian ; Koh, Dow-Mu ; Collins, David J. ; d’Arcy, James ; Padhani, Anwar R. ; Leach, Martin O. ; Judson, Ian R. ; Rustin, Gordon J.

Background. This open-label phase I dose-escalation study investigated the safety, efficacy, pharmacokinetics (PK), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) effects of the oral angiokinase inhibitor nintedanib in patients with advanced solid tumors. Methods. Nintedanib was administered once daily continuously, starting at 100 mg and later amended to allow evaluation of 250 mg b.i.d. The primary endpoint was maximum tolerated dose (MTD). DCE-MRI studies were performed [...]

Mené sur 56 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue la dose maximale tolérée d'un composé appelé AZD2014, un inhibiteur de m-TORC 1/2, et analyse divers paramètres pharmacocinétiques

First-in-human pharmacokinetic and pharmacodynamic study of the dual m-TORC 1/2 inhibitor, AZD2014

Basu, Bristi ; Dean, Emma ; Puglisi, Martina ; Greystroke, Alastair ; Ong, Michael ; Burke, Wendy M ; Cavallin, Maria ; Bigley, Graham ; Womack, Chris ; Harrington, Elizabeth A ; Green, Stephen ; Oelmann, Elisabeth ; de Bono, Johann S. ; Ranson, Malcolm R ; Banerji, Udai

Purpose: AZD2014 is a novel, oral, m-TORC 1/2 inhibitor which has shown in-vitro and in-vivo efficacy across a range of preclinical human cancer models. Experimental Design: A rolling six dose escalation was performed to define a maximal tolerated dose (MTD) (Part A) and at MTD a further cohort of patients was treated to further characterize toxicities and perform pre- and post-treatment biopsies (Part B). AZD2014 was administered orally twice a day (BD) continuously. Flow cytometry, ELISA and [...]

Mené sur 24 patients atteints d'un myélome multiple récidivant ou réfractaire, cet essai de phase I/IB évalue la dose maximale tolérée d'un composé appelé NVP-AUY922, un inhibiteur de la protéine de choc thermique Hsp 90, seul ou en combinaison avec du bortézomib

Phase 1/1B trial of the heat shock protein 90 inhibitor NVP-AUY922 as monotherapy or in combination with bortezomib in patients with relapsed or refractory multiple myeloma

Seggewiss-Bernhardt, Ruth ; Bargou, Ralf C. ; Goh, Yeow Tee ; Stewart, A. Keith ; Spencer, Andrew ; Alegre, Adrian ; Bladé, Joan ; Ottmann, Oliver G. ; Fernandez-Ibarra, Cristina ; Lu, Hong ; Pain, Scott ; Akimov, Mikhail ; Iyer, Swaminathan Padmanabhan

BACKGROUND : NVP-AUY922 (AUY; Luminespib) with or without bortezomib showed preclinical activity against multiple myeloma (MM) cells. This phase 1/1B study assessed NVP-AUY922 alone and with bortezomib in patients with relapsed or refractory MM. METHODS : Dose escalation was guided by an adaptive Bayesian logistic regression model. In phase 1, patients who progressed after 2 to 4 prior therapies received NVP-AUY922 intravenously once weekly. In phase 1B, patients who progressed after 2 or fewer [...]

Mené en France sur des patients atteints d'un carcinome papillaire à cellules rénales de stade localement avancé ou métastatique (15 type 1, 46 type 2), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité du sunitinib en traitement de première ligne

First-line treatment with sunitinib for type 1 and type 2 locally advanced or metastatic papillary renal cell carcinoma: a phase II study (SUPAP) by the French Genitourinary Group (GETUG)

Ravaud, A. ; Oudard, S. ; De Fromont, M. ; Chevreau, C. ; Gravis, G. ; Zanetta, S. ; Theodore, C. ; Jimenez, M. ; Sevin, E. ; Laguerre, B. ; Rolland, F. ; Ouali, M. ; Culine, S. ; Escudier, B.

Background : Papillary renal cell carcinoma (PRCC), type 1 and type 2, represents 10 to 15% of renal cell carcinomas (RCC). There is no standard 1st line treatment for metastatic PRCC (mPRCC). Anti-angiogenics have shown activity in retrospective studies but no prospective studies in pure papillary histology have been reported, but one with foretinib. Patients and methods : A prospective phase II study evaluated sunitinib in 1st line treatment of mPRCC. The primary end-point was overall [...]

Mené sur 34 patients atteints d'un carcinome à cellules rénales de stade avancé réfractaire, cet essai évalue l'efficacité et la toxicité du nivolumab, un anticorps anti PD-1

Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab

McDermott, David F. ; Drake, Charles G. ; Sznol, Mario ; Choueiri, Toni K. ; Powderly, John D. ; Smith, David C. ; Brahmer, Julie R. ; Carvajal, Richard D. ; Hammers, Hans J. ; Puzanov, Igor ; Hodi, F. Stephen ; Kluger, Harriet M. ; Topalian, Suzanne L. ; Pardoll, Drew M. ; Wigginton, Jon M. ; Kollia, Georgia D. ; Gupta, Ashok ; McDonald, Dan ; Sankar, Vindira ; Sosman, Jeffrey A. ; Atkins, Michael B.

Purpose : Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts. Patients and Methods : A total of 34 patients with previously [...]

Mené sur 19 patients atteints d'un sarcome récidivant/réfractaire HER2+, cet essai de phase I/II évalue l'efficacité, du point de vue de la survie globale, et la toxicité d'un traitement à base de lymphocytes T modifiés pour exprimer un récepteur d'antigène chimérique contre HER2

Human Epidermal Growth Factor Receptor 2 (HER2) –Specific Chimeric Antigen Receptor–Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma

Ahmed, Nabil ; Brawley, Vita S. ; Hegde, Meenakshi ; Robertson, Catherine ; Ghazi, Alexia ; Gerken, Claudia ; Liu, Enli ; Dakhova, Olga ; Ashoori, Aidin ; Corder, Amanda ; Gray, Tara ; Wu, Meng-Fen ; Liu, Hao ; Hicks, John ; Rainusso, Nino ; Dotti, Gianpietro ; Mei, Zhuyong ; Grilley, Bambi ; Gee, Adrian ; Rooney, Cliona M. ; Brenner, Malcolm K. ; Heslop, Helen E. ; Wels, Winfried S. ; Wang, Lisa L. ; Anderson, Peter ; Gottschalk, Stephen

Purpose : The outcome for patients with metastatic or recurrent sarcoma remains poor. Adoptive therapy with tumor-directed T cells is an attractive therapeutic option but has never been evaluated in sarcoma. Patients and Methods : We conducted a phase I/II clinical study in which patients with recurrent/refractory human epidermal growth factor receptor 2 (HER2) –positive sarcoma received escalating doses (1 × 104/m2 to 1 × 108/m2) of T cells expressing an HER2-specific chimeric antigen receptor [...]

Menée sur une cohorte de 1 076 patients atteints d'un cancer du poumon non à petites cellules de stade IIIA traité par chirurgie entre 2003 et 2005, cette étude évalue, du point de vue des résultats pathologiques et de la survie globale, l'efficacité d'une chimioradiothérapie néoadjuvante par rapport à une chimiothérapie seule

Comparative effectiveness of neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery for patients with stage IIIA non-small cell lung cancer

Sher, David J. ; Fidler, Mary Jo ; Liptay, Michael J. ; Koshy, Matthew

Objectives : The optimal neoadjuvant therapy prior to surgical resection of stage IIIA non-small cell lung cancer (NSCLC) is controversial, as data support both preoperative chemoradiotherapy (N-CRT) and chemotherapy (N-CTX). We evaluated the comparative effectiveness of N-CRT versus N-CTX in stage IIIA patients in the National Cancer Database (NCDB). Methods : Patients in the NCDB with stage IIIA NSCLC treated with N-CRT or N-CTX and surgery between 2003-2005 were analyzed. Outcomes included [...]

Cet article passe en revue les stratégies permettant de personnaliser les approches thérapeutiques combinant une radiothérapie guidée par l'imagerie et un traitement anti-androgénique chez les patients atteints d'un cancer de la prostate

Synergistic action of image-guided radiotherapy and androgen deprivation therapy

Locke, Jennifer A. ; Pra, Alan Dal ; Supiot, Stephane ; Warde, Padraig ; Bristow, Robert G.

The combined use of androgen deprivation therapy (ADT) and image-guided radiotherapy (IGRT) can improve overall survival in aggressive, localized prostate cancer. However, owing to the adverse effects of prolonged ADT, it is imperative to identify the patients who would benefit from this combined-modality therapy relative to the use of IGRT alone. Opportunities exist for more personalized approaches in treating aggressive, locally advanced prostate cancer. Biomarkers[mdash]such as disseminated [...]

Mené sur 740 patientes atteintes d'un cancer opérable du sein HR+ avant la ménopause, cet essai de phase III évalue le bénéfice, en termes de survie, d'une ovariectomie adjuvante réalisée durant la phase lutéale du cycle menstruel

Timing of Adjuvant Surgical Oophorectomy in the Menstrual Cycle and Disease-Free and Overall Survival in Premenopausal Women With Operable Breast Cancer

Love, Richard R. ; Laudico, Adriano V. ; Van Dinh, Nguyen ; Allred, D. Craig ; Uy, Gemma B. ; Quang, Le Hong ; Salvador, Jonathan Disraeli S. ; Siguan, Stephen Sixto S. ; Mirasol-Lumague, Maria Rica ; Tung, Nguyen Dinh ; Benjaafar, Noureddine ; Navarro, Narciso S. ; Quy, Tran Tu ; De La Peña, Arturo S. ; Dofitas, Rodney B. ; Bisquera, Orlino C. ; Linh, Nguyen Dieu ; To, Ta Van ; Young, Gregory S. ; Hade, Erinn M. ; Jarjoura, David

Background : For women with hormone receptor–positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes. Methods : Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual [...]

Cet article présente les données ayant servi de base à l'autorisation de mise sur le marché du belinostat, un inhibiteur d'histone désacétylase, délivrée en juillet 2014 par l'autorité réglementaire américaine pour le traitement des patients atteints d'un lymphome T périphérique récidivant ou réfractaire

FDA Approval: Belinostat for the Treatment of Patients with Relapsed or Refractory Peripheral T-cell Lymphoma

Lee, Hyon-Zu ; Kwitkowski, Virginia E. ; Del Valle, Pedro L. ; Ricci, M. Stacey ; Saber, Haleh ; Habtemariam, Bahru A. ; Bullock, Julie ; Bloomquist, Erik ; Shen, Yuan Li ; Chen, Xiao-Hong ; Brown, Janice ; Mehrotra, Nitin ; Dorff, Sarah ; Charlab, Rosane ; Kane, Robert C ; Kaminskas, Edvardas ; Justice, Robert ; Farrell, Ann T. ; Pazdur, Richard

On July 3, 2014, the FDA granted accelerated approval for belinostat (BELEODAQ®; Spectrum Pharmaceuticals, Inc.), a histone deacetylase inhibitor, for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). A single-arm, open-label, multicenter, international trial in the indicated patient population was submitted in support of the application. Belinostat was administered intravenously at a dose of 1000 mg/m2 over 30 minutes once daily on Days 1-5 of a 21-day [...]