Menée sur des lignées cellulaires dérivées de divers types tumoraux (côlon-rectum, poumon, rein, glioblastome), cette étude montre que la suppression de la voie de signalisation p38MAPKα ne confère pas de radiorésistance aux cellules tumorales mais que cette signalisation est nécessaire pour l'utilisation du 5-fluorouracile comme radiosensibilisant

Abrogation of the p38 MAPKα signaling pathway does not promote radioresistance but its activity is required for 5-Fluorouracil-associated radiosensitivity

de la Cruz-Morcillo, Miguel A. ; García-Cano, Jesús ; Arias-González, Laura ; García-Gil, Elena ; Artacho-Cordón, Francisco ; Ríos-Arrabal, Sandra ; Valero, María Ll ; Cimas, Francisco J. ; Serrano-Oviedo, Leticia ; Villas, María V. ; Romero-Fernández, Jesús ; Núñez, María I. ; Sánchez-Prieto, Ricardo

The p38 Mitogen Activated Protein Kinase (MAPK) signaling pathway has become a major player in the response to DNA-damage. A growing body of evidences has been relating this signaling pathway to the cellular response to ionizing radiation (IR), suggesting a role in radioresistance. Here, we study the implication of this signaling pathway in the response to IR in terms of radioresistance. To this end we used 10 different cell lines derived from several types of tumours (colorectal, non-small [...]

Menée sur 80 patients atteints d'un cancer du poumon non à petites cellules ayant subi une résection incomplète de type R1 entre 2002 et 2011, cette étude rétrospective évalue, en fonction de la présence ou non d'une extension extracapsulaire ganglionnaire et du point de vue de l'échec loco-régional et du taux de survie globale à 3 ans, l'efficacité d'une radiothérapie tridimensionnelle post-opératoire planifiée

Patterns of failure after postoperative radiotherapy for incompletely resected (R1) non-small cell lung cancer: Implications for radiation target volume design

Olszyna-Serementa, Marta ; Socha, Joanna ; Wierzchowski, Marek ; Kępka, Lucyna

Objective Overall survival (OS) and pattern of failure in R1-resected non-small cell lung cancer (NSCLC) patients treated with 3D-planned postoperative radiotherapy (PORT) was retrospectively evaluated. The outcomes and patterns of failure in patients with (+) and without (−) extracapsular nodal extension (ECE) were compared and analyzed with respect to the radiation target volume design. Materials and methods Eighty R1-resected (37 ECE+ and 43 ECE−) patients received PORT (60 Gy, 2 Gy daily) [...]

Menée sur 58 patients traités entre 2004 et 2011 pour un cancer primitif du poumon ou une tumeur récidivant localement (âge : 48 à 90 ans ; durée médiane de suivi : 23,8 mois), cette étude évalue l'efficacité, du point de vue du taux de contrôle local à 2 ans et de la survie, et la toxicité d'une radiothérapie ablative stéréotaxique à forte dose de rayonnements après tomographie numérique par émission de positrons à base de fluorodésoxyglucose (18F)

Long-term clinical experience of high-dose ablative lung radiotherapy: High pre-treatment [18F]Fluorodeoxyglucose-positron emission tomography maximal standardized uptake value of the primary tumor adversely affects treatment outcome

Lee, Dong Soo ; Kim, Yeon Sil ; Yoo, Ie Ryung ; Kang, Young Nam ; Kim, Seoung Jun ; Oh, Jin Kyung ; Kim, Young Kyoon ; Wang, Young Pil ; Park, Jae Gil ; Kang, Jin-Hyoung ; Han, Dae Hee ; Ahn, Myung Im ; Lee, Kyo Young

Purpose The aim of this study was to report the long-term clinical experience with lung stereotactic ablative radiotherapy (SABR). Methods Between April 2004 and December 2011, 58 of 92 consecutive lung SABR cases were treated with a curative purpose and were eligible for inclusion. Forty patients were treated for primary lung cancer, and eighteen were treated for locally confined recurrent tumors. The majority of the cases were medically inoperable (65.5%). A median five fractions with a total [...]

Menée sur 1 070 patientes atteintes d'un cancer du sein sans métastase ganglionnaire et traité par lumpectomie, cette étude évalue l'impact du délai entre le traitement chirurgical et le début de la radiothérapie sur la survie sans métastase distante et la survie spécifique des patientes

Timing of radiotherapy in breast-conserving therapy: a large prospective cohort study of node-negative breast cancer patients without adjuvant systemic therapy

Jobsen, J. J. ; van der Palen, J. ; Baum, M. ; Brinkhuis, M. ; Struikmans, H.

Background : To investigate the issue of timing of radiation therapy (RT) after lumpectomy in relation to recurrences and outcome. Methods : Analysis was done on 1107 breast-conserving therapies (BCT) with 1070 women, all without lymph node metastasis and without any adjuvant systemic therapy. Timing was defined as time from lumpectomy till RT. Patients were categorised into tertiles: <45 days, 45–56 days, and 57–112 days. Results : Local control did not show a difference between the tertiles. [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude évalue l'activité antitumorale d'un anticorps monoclonal anti KIT pour le traitement des tumeurs stromales gastrointestinales résistantes à l'imatinib

Anti-KIT monoclonal antibody inhibits imatinib-resistant gastrointestinal stromal tumor growth

Edris, Badreddin ; Willingham, Stephen B. ; Weiskopf, Kipp ; Volkmer, Anne K. ; Volkmer, Jens-Peter ; Mühlenberg, Thomas ; Montgomery, Kelli D. ; Contreras-Trujillo, Humberto ; Czechowicz, Agnieszka ; Fletcher, Jonathan A. ; West, Robert B. ; Weissman, Irving L. ; van de Rijn, Matt

Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract and arises from the interstitial cells of Cajal. It is characterized by expression of the receptor tyrosine kinase CD117 (KIT). In 70–80% of GIST cases, oncogenic mutations in KIT are present, leading to constitutive activation of the receptor, which drives the proliferation of these tumors. Treatment of GIST with imatinib, a small-molecule tyrosine kinase inhibitor, inhibits KIT-mediated signaling [...]

Cet article passe en revue les perspectives offertes par le ciblage de la voie de signalisation HGF/c-MET pour le traitement d'un carcinome hépatocellulaire de stade avancé

Targeting the HGF/c-MET Pathway in Hepatocellular Carcinoma

Goyal, Lipika ; Muzumdar, Mandar D. ; Zhu, Andrew X.

Hepatocellular carcinoma (HCC) is a significant cause of cancer-related morbidity and mortality worldwide. Despite improvements in local therapies including surgical resection, liver transplantation, and transarterial embolization, the prognosis remains poor for the majority of patients who develop recurrence or present with advanced disease. Systemic therapy with the tyrosine kinase inhibitor sorafenib represents a milestone in advanced HCC, but provides a limited survival benefit. Ongoing [...]

A partir de données de séquençage du transcriptome portant sur 482 échantillons tumoraux de 25 localisations différentes, cette étude identifie des protéines kinases susceptibles de servir de cibles thérapeutiques

Outlier Kinase Expression by RNA Sequencing as Targets for Precision Therapy

Kothari, Vishal ; Wei, Iris ; Shankar, Sunita ; Kalyana-Sundaram, Shanker ; Wang, Lidong ; Ma, Linda W. ; Vats, Pankaj ; Grasso, Catherine S. ; Robinson, Dan R. ; Wu, Yi-Mi ; Cao, Xuhong ; Simeone, Diane M. ; Chinnaiyan, Arul M. ; Kumar-Sinha, Chandan

Protein kinases represent the most effective class of therapeutic targets in cancer; therefore, determination of kinase aberrations is a major focus of cancer genomic studies. Here, we analyzed transcriptome sequencing data from a compendium of 482 cancer and benign samples from 25 different tissue types, and defined distinct “outlier kinases” in individual breast and pancreatic cancer samples, based on highest levels of absolute and differential expression. Frequent outlier kinases in breast [...]

Menée in vitro et sur des patients inclus dans des essais cliniques, cette étude met en évidence les effets d'un virus oncolytique, JX-594, sur le réseau vasculaire tumoral

Oncolytic Vaccinia Virus Disrupts Tumor-Associated Vasculature in Humans

Breitbach, Caroline J. ; Arulanandam, Rozanne ; De Silva, Naomi ; Thorne, Steve H. ; Patt, Richard ; Daneshmand, Manijeh ; Moon, Anne ; Ilkow, Carolina ; Burke, James ; Hwang, Tae-Ho ; Heo, Jeong ; Cho, Mong ; Chen, Hannah ; Angarita, Fernando A. ; Addison, Christina ; McCart, J. Andrea ; Bell, John C. ; Kirn, David H.

Efforts to selectively target and disrupt established tumor vasculature have largely failed to date. We hypothesized that a vaccinia virus engineered to target cells with activation of the ras/MAPK signaling pathway (JX-594) could specifically infect and express transgenes (hGM-CSF, β-galactosidase) in tumor-associated vascular endothelial cells in humans. Efficient replication and transgene expression in normal human endothelial cells in vitro required either VEGF or FGF-2 stimulation. [...]

Menée in vitro et in vivo, cette étude évalue l’activité antitumorale d’une petite molécule, TIC10, induisant une surexpression du gène suppresseur de tumeurs TRAIL et susceptible de franchir la barrière hémato-encéphalique

Dual Inactivation of Akt and ERK by TIC10 Signals Foxo3a Nuclear Translocation, TRAIL Gene Induction, and Potent Antitumor Effects

Allen, Joshua E. ; Krigsfeld, Gabriel ; Mayes, Patrick A. ; Patel, Luv ; Dicker, David T. ; Patel, Akshal S. ; Dolloff, Nathan G. ; Messaris, Evangelos ; Scata, Kimberly A. ; Wang, Wenge ; Zhou, Jun-Ying ; Wu, Gen Sheng ; El-Deiry, Wafik S.

Recombinant tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is an antitumor protein that is in clinical trials as a potential anticancer therapy but suffers from drug properties that may limit efficacy such as short serum half-life, stability, cost, and biodistribution, particularly with respect to the brain. To overcome such limitations, we identified TRAIL-inducing compound 10 (TIC10), a potent, orally active, and stable small molecule that transcriptionally induces TRAIL in a [...]

Menée in vitro sur des cellules prélevées chez 54 enfants atteints d'une leucémie lymphoblastique aiguë avant l'âge d'un an, cette étude met en évidence des mécanismes d'action de l'obatoclax

Potent obatoclax cytotoxicity and activation of triple death mode killing across infant acute lymphoblastic leukemia (ALL)

Urtishak, Karen A. ; Edwards, Alena Y.Z. ; Wang, Li-San ; Hudome, Amanda ; Robinson, Blaine W. ; Barrett, Jeffrey S. ; Cao, Kajia ; Cory, Lori ; Moore, Jonni S. ; Bantly, Andrew D. ; Yu, Qian-Chun ; Chen, I-Ming L. ; Atlas, Susan R. ; Willman, Cheryl L. ; Kundu, Mondira ; Carroll, Andrew J. ; Heerema, Nyla A. ; Devidas, Meenakshi ; Hilden, Joanne M. ; Dreyer, ZoAnn E. ; Hunger, Stephen P. ; Reaman, Gregory H. ; Felix, Carolyn A.

Survival in infants <1 year old with ALL is inferior whether MLL is rearranged (R) or germline (G). MLL translocations confer chemotherapy resistance and infants experience excess complications. We characterized in vitro sensitivity to the pan-anti-apoptotic BCL-2 family inhibitor obatoclax mesylate in diagnostic leukemia cells from 54 infants with ALL/bilineal acute leukemia because of the role of prosurvival BCL-2 proteins in resistance, their imbalanced expression in infant ALL, and evidence [...]

Menée in vitro, cette étude met en évidence des mécanismes de résistance à un traitement par inhibiteur de JAK2 dans les myélofibroses

Intrinsic resistance to JAK2 inhibition in myelofibrosis

Kalota, Anna ; Jeschke, Grace R. ; Carroll, Martin ; Hexner, Elizabeth O.

Purpose: Recent results have demonstrated that myeloproliferative neoplasms (MPN) are strongly associated with constitutive activation of the JAK2 tyrosine kinase. However, JAK2 inhibitors currently approved or under development for treating myeloproliferative neoplasms do not selectively deplete the malignant clone, and the inhibition of activity of the drug target (JAK2) has not been rigorously evaluated in clinical studies. Therefore in this study we developed an in vitro assay to gain [...]

Menée à l'aide de modèles murins, cette étude met en évidence le rôle joué par le système immunitaire dans le mécanisme d'action du vemurafenib pour le traitement d'un mélanome présentant la mutation V600E du gène BRAF

Host immunity contributes to the anti-melanoma activity of BRAF inhibitors

Knight, Deborah A. ; Ngiow, Shin Foong ; Li, Ming ; Parmenter, Tiffany ; Mok, Stephen ; Cass, Ashley ; Haynes, Nicole M. ; Kinross, Kathryn ; Yagita, Hideo ; Koya, Richard C. ; Graeber, Thomas G. ; Ribas, Antoni ; McArthur, Grant A. ; Smyth, Mark J.

The BRAF mutant, BRAFV600E, is expressed in nearly half of melanomas, and oral BRAF inhibitors induce substantial tumor regression in patients with BRAFV600E metastatic melanoma. The inhibitors are believed to work primarily by inhibiting BRAFV600E-induced oncogenic MAPK signaling; however, some patients treated with BRAF inhibitors exhibit increased tumor immune infiltration, suggesting that a combination of BRAF inhibitors and immunotherapy may be beneficial. We used two relatively resistant [...]

Menée à l'aide de modèles murins, cette étude évalue l'activité antitumorale de nanoparticules chargées de petits ARN interférents pour le traitement d'un cancer métastatique de l'ovaire

Enhancing chemotherapy response with sustained EphA2 silencing using multistage vector delivery

Shen, Haifa ; Rodriguez-Aguayo, Cristian ; Xu, Rong ; Gonzalez-Villasana, Vianey ; Mai, Junhua ; Huang, Yi ; Zhang, Guo-Dong ; Guo, Xiaojing ; Bao, Litao ; Guoting, Qin ; Deng, Xiaoyong ; Li, Qingpo ; Erm, Donald ; Sakamoto, Jason H. ; Liu, Xuewu ; Chavez-Reyes, Arturo ; Han, Hee-Dong ; Sood, Anil K. ; Ferrari, Mauro ; Lopez-Berestein, Gabriel

Purpose: RNA interference has the potential to specifically knock down target gene expression, and thereby transform cancer therapy. However, lack of effective delivery of small inhibitory RNA (siRNA) has dramatically limited its in vivo applications. We have developed a multistage vector (MSV) system, composed of discoidal porous silicon particles loaded with nanotherapeutics, that directs effective delivery and sustained release of siRNA in tumor. In this study, we evaluated therapeutic [...]

Cet article passe en revue les perspectives offertes par le ciblage des voies de signalisation inflammatoire pour le traitement d'un adénocarcinome canalaire du pancréas

Exploiting inflammation for therapeutic gain in pancreatic cancer

Steele, C. W. ; Jamieson, N. B. ; Evans, T. R. J. ; McKay, C. J. ; Sansom, O. J. ; Morton, J. P. ; Carter, C. R.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with <5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and [...]

Menée à l'aide de modèles murins, cette étude met en évidence le rôle de la signalisation HER4 dans la réponse à une chimiothérapie pour un cancer du poumon non à petites cellules

Blocking NRG1 and Other Ligand-Mediated Her4 Signaling Enhances the Magnitude and Duration of the Chemotherapeutic Response of Non–Small Cell Lung Cancer

Hegde, Ganapati V. ; de la Cruz, Cecile C. ; Chiu, Cecilia ; Alag, Navneet ; Schaefer, Gabriele ; Crocker, Lisa ; Ross, Sarajane ; Goldenberg, David ; Merchant, Mark ; Tien, Janet ; Shao, Lily ; Roth, Leslie ; Tsai, Siao-Ping ; Stawicki, Scott ; Jin, Zhaoyu ; Wyatt, Shelby K. ; Carano, Richard A. D. ; Zheng, Yanyan ; Sweet-Cordero, E. Alejandro ; Wu, Yan ; Jackson, Erica L.

Although standard chemotherapies are commonly used to treat most types of solid tumors, such treatment often results in inadequate response to, or relapse after, therapy. This is particularly relevant for lung cancer because most patients are diagnosed with advanced-stage disease and are treated with frontline chemotherapy. By studying the residual tumor cells that remain after chemotherapy in several in vivo non–small cell lung cancer models, we found that these cells have increased levels of [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude évalue l'activité d'un composé appelé AUY922, un inhibiteur de la protéine de choc thermique HSP90, seul ou en combinaison avec le trastuzumab, pour le traitement d'un cancer du sein ou de l'estomac HER2+

Inhibition of HSP90 with AUY922 induces synergy in HER2 amplified trastuzumab resistant breast and gastric cancer

Wainberg, Zev A ; Anghel, Adrian ; Rogers, Amy M ; Desai, Amrita J ; Kalous, Ondrej ; Conklin, Dylan ; Ayala, Raul ; O'Brien, Neil A ; Quadt, Cornelia ; Akimov, Mikhail ; Slamon, Dennis J ; Finn, Richard S.

Heat Shock Protein 90 (HSP90) enables the activation of many client proteins of which the most clinically validated is HER2. NVP-AUY922, a potent HSP90 inhibitor, is currently in Phase II clinical trials. To explore its potential clinical utility in HER2-amplified breast and gastric cancers, we evaluated the effect of AUY922 alone and in combination with trastuzumab in both trastuzumab-sensitive and resistant models. A panel of 16 human gastric and 45 breast cancer cell lines, including 16 [...]

Mené sur 30 patients atteints d'un carcinome hépatocellulaire de stade avancé, cet essai randomisé de phase II évalue, du point de vue du taux de réponse tumorale et de la survie, l'efficacité de deux doses d'un virus oncolytique, JX-594, injecté dans les tumeurs

Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer

Heo, Jeong ; Reid, Tony ; Ruo, Leyo ; Breitbach, Caroline J. ; Rose, Steven ; Bloomston, Mark ; Cho, Mong ; Lim, Ho Yeong ; Chung, Hyun Cheol ; Kim, Chang Won ; Burke, James ; Lencioni, Riccardo ; Hickman, Theresa ; Moon, Anne ; Lee, Yeon Sook ; Kim, Mi Kyeong ; Daneshmand, Manijeh ; Dubois, Kara ; Longpre, Lara ; Ngo, Minhtran ; Rooney, Cliona ; Bell, John C. ; Rhee, Byung-Geon ; Patt, Richard ; Hwang, Tae-Ho ; Kirn, David H.

Oncolytic viruses and active immunotherapeutics have complementary mechanisms of action (MOA) that are both self amplifying in tumors, yet the impact of dose on subject outcome is unclear. JX-594 (Pexa-Vec) is an oncolytic and immunotherapeutic vaccinia virus. To determine the optimal JX-594 dose in subjects with advanced hepatocellular carcinoma (HCC), we conducted a randomized phase 2 dose-finding trial (n = 30). Radiologists infused low- or high-dose JX-594 into liver tumors (days 1, 15 and [...]

Mené sur 1 895 patients atteints d'un sarcome incurable des tissus mous ayant progressé après un traitement de référence, cet essai évalue l'efficacité, du point de vue du taux de réponse objective et de la survie globale, et la toxicité de la trabectédine

Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: results of a worldwide expanded access program study

Samuels, B. L. ; Chawla, S. ; Patel, S. ; von Mehren, M. ; Hamm, J. ; Kaiser, P. E. ; Schuetze, S. ; Li, J. ; Aymes, A. ; Demetri, G. D.

Background This expanded access program (EAP) was designed to provide trabectedin access for patients with incurable soft tissue sarcoma (STS) following progression of disease with standard therapy. The outcomes of trial participants accrued over approximately 5 years are reported. Patients and methods Adult patients with advanced STS of multiple histologies, including leiomyosarcoma and liposarcoma (L-sarcomas), following relapse or disease progression following standard-of-care chemotherapy, [...]

Mené sur 45 patientes coréennes atteintes d'un cancer du sein triplement négatif, cet essai de phase II évalue, du point de vue du taux de réponse pathologique complète, un traitement néoadjuvant combinant bevacizumab, docétaxel et carboplatine

Multicentre phase II trial of bevacizumab combined with docetaxel–carboplatin for the neoadjuvant treatment of triple-negative breast cancer (KCSG BR-0905)

Kim, H. R. ; Jung, K. H. ; Im, S.-A. ; Im, Y.-H. ; Kang, S. Y. ; Park, K. H. ; Lee, S. ; Kim, S.-B. ; Lee, K.-H. ; Ahn, J. S. ; Kim, S. I. ; Sohn, J. H.

Background This phase II neoadjuvant trial evaluated bevacizumab–docetaxel and carboplatin in triple-negative breast cancer. Patients and methods Women with hormone receptor- and human epidermal growth factor receptor 2 (HER2)-negative, stage II/III breast cancer received six cycles of 75 mg/m2 docetaxel, carboplatin (AUC = 5) and 15 mg/kg bevacizumab every 21 days. The primary end point was pathological complete response (pCR) in breasts and axillary lymph nodes (ALN). Results Forty-five [...]

Mené sur 137 patientes atteintes d'un cancer du sein HER2+ métastatique ou récidivant, cet essai randomisé de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un conjugué anticorps-médicament, T-DM1, combiné au docétaxel en traitement de première ligne

Phase II Randomized Study of Trastuzumab Emtansine Versus Trastuzumab Plus Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2–Postive Metastatic Breast Cancer

Hurvitz, Sara A. ; Dirix, Luc ; Kocsis, Judit ; Bianchi, Giulia V. ; Lu, Janice ; Vinholes, Jeferson ; Guardino, Ellie ; Song, Chunyan ; Tong, Barbara ; Ng, Vivian ; Chu, Yu-Waye ; Perez, Edith A.

Purpose Trastuzumab emtansine (T-DM1), an antibody-drug conjugate composed of the cytotoxic agent DM1 conjugated to trastuzumab via a stable thioether linker, has shown clinical activity in single-arm studies enrolling patients with human epidermal growth factor receptor 2 (HER2) –positive metastatic breast cancer (MBC) whose disease had progressed on HER2-targeted therapy in the metastatic setting. Patients And Methods Patients (N = 137) with HER2-positive MBC or recurrent locally advanced [...]

Mené sur 24 patients atteints d'un adénocarcinome localement avancé de la jonction œsophago-gastrique, cet essai prospectif multicentrique de phase I/II évalue la toxicité limitant la dose, la dose maximale tolérable et, du point de vue du taux de réponse globale et de la survie sans progression, l'efficacité d'une chimioradiothérapie néoadjuvante à base de docétaxel et d'oxaliplatine

Prospective, open, multi-centre phase I/II trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and oxaliplatin in patients with adenocarcinoma of the oesophagogastric junction

Moehler, Markus ; Gockel, Ines ; Roessler, Hans-Peter ; Arnold, Dirk ; Trarbach, Tanja ; Thomaidis, Thomas ; Klautke, Gunther ; Rodel, Claus ; Brenner, Baruch ; Lang, Hauke ; Galle, Peter ; Schimanski, Carl ; Schmidberger, Heinz

BACKGROUND:This phase I/II-trial assessed the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of neoadjuvant radiochemotherapy (RCT) with docetaxel and oxaliplatin in patients with locally advanced adenocarcinoma of the oesophagogastric junction.METHODS:Patients received neoadjuvant radiotherapy (50.4 Gy) together with weekly docetaxel (20 mg/m2 at dose level (DL) 1 and 2, 25 mg/m2 at DL 3) and oxaliplatin (40 mg/m2 at DL 1, 50 mg/m2 at DL 2 and 3) over 5 weeks. The primary [...]

Cet article passe en revue les études récentes concernant la prise en charge thérapeutique d'un cancer épithélial avancé de l'ovaire

Latest research and treatment of advanced-stage epithelial ovarian cancer

Coleman, Robert L. ; Monk, Bradley J. ; Sood, Anil K. ; Herzog, Thomas J.

The natural history of ovarian cancer continues to be characterized by late-stage presentation, metastatic bulky disease burden and stagnant mortality statistics, despite prolific drug development. Robust clinical investigation, particularly with modifications to primary treatment surgical goals and adjuvant therapy are increasing median progression-free survival and overall survival, although the cure rates have been affected only modestly. Maintenance therapy holds promise, but studies have [...]

Cet article passe en revue les études récentes concernant les nouvelles stratégies thérapeutiques avec radiothérapie ou chimioradiothérapie pour traiter un cancer du poumon non à petites cellules

New Radiotherapy and Chemoradiotherapy Approaches for Non–Small-Cell Lung Cancer

Salama, Joseph K. ; Vokes, Everett E.

Recent advances in systemic cytotoxic and molecularly targeted therapies coupled with technologic strides in radiotherapy have the potential to improve outcomes for patients with non–small-cell lung cancer (NSCLC). Investigations are ongoing to identify optimal cytotoxin-based chemoradiotherapy platforms. The influence of specific histologic and molecular mutation status on the combination of targeted therapies and radiotherapy is also being actively studied. Although there are no convincing [...]

Mené sur 126 patients atteints d'un cancer du poumon non à petites cellules avec 1 à 3 métastases cérébrales, cet essai de phase III évalue, du point de vue de la toxicité et de la survie globale, l'intérêt d'ajouter le témozolomide ou l'erlotinib à un traitement combinant une radiothérapie du cerveau entier et une radiochirurgie stéréotaxique

A Phase 3 Trial of Whole Brain Radiation Therapy and Stereotactic Radiosurgery Alone Versus WBRT and SRS With Temozolomide or Erlotinib for Non-Small Cell Lung Cancer and 1 to 3 Brain Metastases: Radiation Therapy Oncology Group 0320

Sperduto, Paul W. ; Wang, Meihua ; Robins, H. Ian ; Schell, Michael C. ; Werner-Wasik, Maria ; Komaki, Ritsuko ; Souhami, Luis ; Buyyounouski, Mark K. ; Khuntia, Deepak ; Demas, William ; Shah, Sunjay A. ; Nedzi, Lucien A. ; Perry, Gad ; Suh, John H. ; Mehta, Minesh P.

A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with [...]

Cet article présente la mise à jour 2013 des recommandations SPIRIT pour la description d'un protocole d'essai clinique

SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials

Chan, An-Wen ; Tetzlaff, Jennifer M. ; Altman, Douglas G. ; Laupacis, Andreas ; Gøtzsche, Peter C. ; Krleža-Jerić, Karmela ; Hróbjartsson, Asbjørn ; Mann, Howard ; Dickersin, Kay ; Berlin, Jesse A. ; Doré, Caroline J. ; Parulekar, Wendy R. ; Summerskill, William S. M. ; Groves, Trish ; Schulz, Kenneth F. ; Sox, Harold C. ; Rockhold, Frank W. ; Rennie, Drummond ; Moher, David

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and [...]

Cet article passe en revue les travaux récents sur la prise en charge d'une leucémie myéloïde aiguë chez les patients adultes

Acute myeloid leukaemia in adults

Ferrara, Felicetto ; Schiffer, Charles A.

The outlook for patients with acute myeloid leukaemia has improved in the past 30 years. Unlike other cancers, much of this progress is attributable to refinement of supportive treatment, rather than the introduction of new drugs. New antibacterial and antifungal agents, antiemetics, and improved transfusion support have decreased the rate of early death, and morbidity and mortality from allogeneic stem cell transplantation has been substantially reduced. However, more than half of young adult [...]