Mené sur 12 patientes atteintes d'un cancer du sein traité par mastectomie, cet essai prospectif évalue la toxicité aigüe et la faisabilité d'une protonthérapie avec ou sans reconstruction mammaire

Proton Therapy for Breast Cancer After Mastectomy: Early Outcomes of a Prospective Clinical Trial

MacDonald, Shannon M. ; Patel, Sagar A. ; Hickey, Shea ; Specht, Michelle ; Isakoff, Steven J. ; Gadd, Michele ; Smith, Barbara L. ; Yeap, Beow Y. ; Adams, Judith ; DeLaney, Thomas F. ; Kooy, Hanne ; Lu, Hsiao-Ming ; Taghian, Alphonse G.

Dosimetric planning studies have described potential benefits for the use of proton radiation therapy (RT) for locally advanced breast cancer. We report acute toxicities and feasibility of proton delivery for 12 women treated with postmastectomy proton radiation with or without reconstruction. Twelve patients were enrolled in an institutional review board-approved prospective clinical trial. The patients were assessed for skin toxicity, fatigue, and radiation pneumonitis during treatment and at [...]

Menée sur 94 patients atteints d'un mélanome choroïdien juxtapapillaire (durée médiane de suivi : 46 mois), cette étude compare, du point de vue des événements indésirables et en fonction de la dose de rayonnements, la toxicité retardée d'une radiothérapie stéréotaxique et d'une curiethérapie à l'iode 125

Dosimetric and Late Radiation Toxicity Comparison Between Iodine-125 Brachytherapy and Stereotactic Radiation Therapy for Juxtapapillary Choroidal Melanoma

Krema, Hatem ; Heydarian, Mostafa ; Beiki-Ardakani, Akbar ; Weisbrod, Daniel ; Xu, Wei ; Laperriere, Normand J. ; Sahgal, Arjun

To compare the dose distributions and late radiation toxicities for 125I brachytherapy (IBT) and stereotactic radiation therapy (SRT) in the treatment of juxtapapillary choroidal melanoma. Ninety-four consecutive patients with juxtapapillary melanoma were reviewed: 30 have been treated with IBT and 64 with SRT. Iodine-125 brachytherapy cases were modeled with plaque simulator software for dosimetric analysis. The SRT dosimetric data were obtained from the Radionics XKnife RT3 software. Mean [...]

Cet article passe en revue les études récentes sur l'intérêt d'une radiothérapie de l'ensemble des ganglions lympatiques pelviens dans le cadre d'une radiothérapie hypofractionnée chez les patients atteints d'un cancer de la prostate avec risque élevé de récidive

Whole-Pelvic Nodal Radiation Therapy in the Context of Hypofractionation for High-Risk Prostate Cancer Patients: A Step Forward

Kaidar-Person, Orit ; Roach, Mack ; Créhange, Gilles

Given the low α/β ratio of prostate cancer, prostate hypofractionation has been tested through numerous clinical studies. There is a growing body of literature suggesting that with high conformal radiation therapy and even with more sophisticated radiation techniques, such as high-dose-rate brachytherapy or image-guided intensity modulated radiation therapy, morbidity associated with shortening overall treatment time with higher doses per fraction remains low when compared with protracted [...]

A partir de données médicales portant sur 150 patients présentant une tumeur rénale bénigne ou maligne (108 cas) traitée entre 2002 et 2008 (âge : 24 à 85 ans ; durée moyenne de suivi : 40 mois), cette étude évalue, du point de vue de la survie spécifique à court terme et de la récidive, l'efficacité d'une ablation tumorale par radiofréquence

Radiofrequency ablation of renal tumours with clinical, radiographical and pathological results

Karam, Jose A. ; Ahrar, Kamran ; Vikram, Raghunandan ; Romero, Claudio A. ; Jonasch, Eric ; Tannir, Nizar M. ; Rao, Priya ; Wood, Christopher G. ; Matin, Surena F.

What's known on the subject? and What does the study add? * Radiological imaging is heavily relied on for follow up after renal ablative therapy. We show that while this is largely reliable, there are quantifiable false negative and false positive findings. A non-involuting zone of ablation should be considered for multisite-directed core biopsies even in the absence of detectable enhancement. Objective * To evaluate our experience with radiofrequency ablation (RFA) for renal masses and to [...]

Menée sur des lignées cellulaires, cette étude met en évidence des mécanismes par lesquels un déficit d'expression de RAD51C confère à des cellules cancéreuses une sensibilité à l'olaparib, un inhibiteur de PARP

RAD51C-deficient cancer cells are highly sensitive to the poly (ADP-ribose) polymerase inhibitor, olaparib

Min, Ahrum ; Im, Seock-Ah ; Yoon, Young-Kwang ; Song, Sang-Hyun ; Nam, Hyun-Jin ; Hur, Hyung-Seok ; Kim, Hwang-Phill ; Lee, Kyung-Hun ; Han, Sae-Won ; Oh, Do-Youn ; Kim, Tae-You ; O`Connor, Mark J ; Kim, Woo-Ho ; Bang, Yung-Jue

A poly (ADP-ribose) polymerase (PARP) inhibitor is a rationally designed targeted therapy for cancers with impaired DNA repair abilities. RAD51C is a paralog of RAD51 that has an important role in the DNA damage response. We found that cell lines sensitive to a novel oral PARP inhibitor, olaparib, had low levels of RAD51C expression using microarray analysis, and we therefore hypothesized that low expression of RAD51C may hamper the DNA repair process, resulting in increased sensitivity to [...]

Cet article passe en revue les perspectives offertes par les connaissances sur le rôle des macrophages associés aux tumeurs pour améliorer l'efficacité des traitements anticancéreux

Macrophage Regulation of Tumor Responses to Anticancer Therapies

De Palma, Michele ; Lewis, Claire E

Tumor-associated macrophages (TAMs) promote key processes in tumor progression, like angiogenesis, immunosuppression, invasion, and metastasis. Increasing studies have also shown that TAMs can either enhance or antagonize the antitumor efficacy of cytotoxic chemotherapy, cancer-cell targeting antibodies, and immunotherapeutic agents depending on the type of treatment and tumor model. TAMs also drive reparative mechanisms in tumors after radiotherapy or treatment with vascular-targeting agents. [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels le fenretinide induit la destruction des cellules souches de leucémie myéloïde aiguë

Preferential eradication of acute myelogenous leukemia stem cells by fenretinide

Zhang, Hui ; Mi, Jian-Qing ; Fang, Hai ; Wang, Zhao ; Wang, Chun ; Wu, Lin ; Zhang, Bin ; Minden, Mark ; Yang, Wen-Tao ; Wang, Huan-Wei ; Li, Jun-Min ; Xi, Xiao-Dong ; Chen, Sai-Juan ; Zhang, Ji ; Chen, Zhu ; Wang, Kan-Kan

Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression, and relapse, and thus represent a critical target for therapeutic intervention. However, relatively few agents have been shown to target LSCs, slowing progress in the treatment of acute myelogenous leukemia (AML). Based on in vitro and in vivo evidence, we report here that fenretinide, a well-tolerated vitamin A derivative, is capable of eradicating LSCs but not normal hematopoietic progenitor/stem cells at [...]

Menée à l'aide de modèles murins, cette étude suggère l'intérêt de la combinaison d'une thérapie ciblée sur Fbw7, pour faire sortir de leur quiescence les cellules initiatrices de leucémie, et de l'imatinib pour le traitement d'une leucémie myéloïde chronique

Ablation of Fbxw7 Eliminates Leukemia-Initiating Cells by Preventing Quiescence

Takeishi, Shoichiro ; Matsumoto, Akinobu ; Onoyama, Ichiro ; Naka, Kazuhito ; Hirao, Atsushi ; Nakayama, Keiichi I

Imatinib eradicates dividing progenitor cells of chronic myeloid leukemia (CML) but does not effectively target nondividing leukemia-initiating cells (LICs); thus, the disease often relapse after its discontinuation. We now show that Fbxw7 plays a pivotal role in maintenance of quiescence in LICs of CML by reducing the level of c-Myc. Abrogation of quiescence in LICs by Fbxw7 ablation increased their sensitivity to imatinib, and the combination of Fbxw7 ablation with imatinib treatment resulted [...]

Menée sur des échantillons prélevés sur 3 patients atteints d'un mélanome et inclus dans un essai clinique de transfert adoptif de lymphocytes T exprimant des récepteurs TCR, cette étude met en évidence la dynamique et l'activité fonctionnelle des cellules transférées

Multifunctional T-cell Analyses to Study Response and Progression in Adoptive Cell Transfer Immunotherapy

Ma, Chao ; Cheung, Ann F. ; Chodon, Thinle ; Koya, Richard C. ; Wu, Zhongqi ; Ng, Charles ; Avramis, Earl ; Cochran, Alistair J. ; Witte, Owen N. ; Baltimore, David ; Chmielowski, Bartosz ; Economou, James S. ; Comin-Anduix, Begonya ; Ribas, Antoni ; Heath, James R.

Adoptive cell transfer (ACT) of genetically engineered T cells expressing cancer-specific T-cell receptors (TCR) is a promising cancer treatment. Here, we investigate the in vivo functional activity and dynamics of the transferred cells by analyzing samples from 3 representative patients with melanoma enrolled in a clinical trial of ACT with TCR transgenic T cells targeted against the melanosomal antigen MART-1. The analyses included evaluating 19 secreted proteins from individual cells from [...]

Cet article passe en revue les travaux récents sur le développement de nouvelles stratégies thérapeutiques dans les myélomes multiples

New Strategies in the Treatment of Multiple Myeloma

Munshi, Nikhil C. ; Anderson, Kenneth C.

Multiple myeloma (MM) is the second most common hematologic malignancy affecting terminally differentiated plasma cells. Although high-dose chemotherapy and autologous stem cell transplantation improved survival in younger patients, the natural history of MM has been changed with the availability of five new agents approved in last 10 years (thalidomide, bortezomib, lenalidomide, liposomal doxorubicin and carfilzomib). Despite this significant improvement in overall outcome, MM remains [...]

Menée à l'aide de xénogreffes, cette étude évalue les effets du selumetinib sur la croissance de tumeurs résistantes à l'anastrozole

Effect of selumetinib on the growth of anastrozole-resistant tumors

Sabnis, GauriJ ; Kazi, Armina ; Golubeva, Olga ; Shah, Preeti ; Brodie, Angela

Despite significant improvement in the treatment outcome of hormone responsive postmenopausal breast cancer, some patients eventually acquire resistance to aromatase inhibitors (AIs). Using our MCF-7Ca xenograft model, we observed that although AIs such as anastrozole initially inhibit tumor growth effectively, tumors eventually began to grow. Our previous data show that anastrozole-resistant tumors upregulate growth factor receptor pathways as they adapt to grow in the low estrogen [...]

Menée à l'aide d'un modèle murin, cette étude évalue l'efficacité d'un virus oncolytique doté d'un antagoniste de CXCR4 pour prévenir la formation de métastases d'un cancer du sein

Targeting CXCL12/CXCR4 signaling with oncolytic virotherapy disrupts tumor vasculature and inhibits breast cancer metastases

Gil, Margaret ; Seshadri, Mukund ; Komorowski, Marcin P. ; Abrams, Scott I. ; Kozbor, Danuta

Oncolytic viruses hold promise for the treatment of cancer, but their interaction with the tumor microenvironment needs to be elucidated for optimal tumor cell killing. Because the CXCR4 receptor for the stromal cell-derived factor-1 (SDF-1/CXCL12) chemokine is one of the key stimuli involved in signaling interactions between tumor cells and their stromal microenvironment, we used oncolytic virotherapy with a CXCR4 antagonist to target the CXCL12/CXCR4 signaling axis in a triple-negative 4T1 [...]

Mené sur 25 patients atteints d'un carcinome hépatocellulaire incurable, cet essai de phase I évalue la dose maximale tolérée, la toxicité et l'activité du temsirolimus en combinaison avec le sorafenib

Temsirolimus combined with sorafenib in hepatocellular carcinoma: a phase I dose-finding trial with pharmacokinetic and biomarker correlates

Kelley, R. K. ; Nimeiri, H. S. ; Munster, P. N. ; Vergo, M. T. ; Huang, Y. ; Li, C.-M. ; Hwang, J. ; Mulcahy, M. F. ; Yeh, B. M. ; Kuhn, P. ; Luttgen, M. S. ; Grabowsky, J. A. ; Stucky-Marshall, L. ; Korn, W. M. ; Ko, A. H. ; Bergsland, E. K. ; Benson, A. B. ; Venook, A. P.

Background Based upon preclinical evidence for improved antitumor activity in combination, this phase I study investigated the maximum-tolerated dose (MTD), safety, activity, pharmacokinetics (PK), and biomarkers of the mammalian target of rapamycin inhibitor, temsirolimus, combined with sorafenib in hepatocellular carcinoma (HCC). Patients and methods Patients with incurable HCC and Child Pugh score ≤B7 were treated with sorafenib plus temsirolimus by 3 + 3 design. The dose-limiting toxicity [...]

Mené sur 34 patients atteints d'une tumeur solide réfractaire, cet essai de phase I évalue la toxicité et l'efficacité d'un analogue synthétique de la thrombospondine, ABT-510, en combinaison avec du bevacizumab

A phase I study of ABT-510 plus bevacizumab in advanced solid tumors

Uronis, Hope E. ; Cushman, Stephanie M. ; Bendell, Johanna C. ; Blobe, Gerard C. ; Morse, Michael A. ; Nixon, Andrew B. ; Dellinger, Andrew ; Starr, Mark D. ; Li, Haiyan ; Meadows, Kellen ; Gockerman, Jon ; Pang, Herbert ; Hurwitz, Herbert I.

Targeting multiple regulators of tumor angiogenesis have the potential to improve treatment efficacy. Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor and ABT-510 is a synthetic analog of thrombospondin, an endogenous angiogenesis inhibitor. Dual inhibition may result in additional benefit. We evaluated the safety, tolerability, and efficacy of the combination of bevacizumab plus ABT-510 in patients with refractory solid tumors. We also explored the [...]

Mené sur 44 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue la dose maximale tolérée d'un traitement combinant sunitinib et gemcitabine

Sunitinib in combination with gemcitabine for advanced solid tumours: a phase I dose-finding study

Michaelson, M. D. ; Zhu, A. X. ; Ryan, D. P. ; McDermott, D. F. ; Shapiro, G. I. ; Tye, L. ; Chen, I. ; Stephenson, P. ; Patyna, S. ; Ruiz-Garcia, A. ; Schwarzberg, A. B.

Background: This phase I, dose-finding study determined the maximum tolerated dose (MTD), safety, and pharmacokinetics of sunitinib plus gemcitabine in patients with advanced solid tumours. Methods: Two schedules with sunitinib (25–50 mg per day) and IV gemcitabine (750–1250 mg m−2) in escalating doses were studied. First, patients received sunitinib on a 4-weeks-on-2-weeks-off schedule (Schedule 4/2) plus gemcitabine on days 1, 8, 22, and 29. Second, patients received sunitinib on a [...]

Mené sur 25 patients atteints d'une leucémie à prolymphocytes T, cet essai de phase II évalue, du point de vue du taux de réponse globale, l'alemtuzumab en complément d'un traitement à base de fludarabine, mitoxantrone et cyclophosphamide

Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia

Hopfinger, Georg ; Busch, Raymonde ; Pflug, Natali ; Weit, Nicole ; Westermann, Anne ; Fink, Anna-Maria ; Cramer, Paula ; Reinart, Nina ; Winkler, Dirk ; Fingerle-Rowson, Günter ; Stilgenbauer, Stephan ; Döhner, Hartmut ; Kandler, Gabriele ; Eichhorst, Barbara ; Hallek, Michael ; Herling, Marco

BACKGROUND: Scarce systematic trial data have prevented uniform therapeutic guidelines for T-cell prolymphocytic leukemia (T-PLL). A central need in this historically refractory tumor is the controlled evaluation of multiagent chemotherapy and its combination with the currently most active single agent, alemtuzumab. METHODS: This prospective multicenter phase 2 trial assessed response, survival, and toxicity of a novel regimen in previously treated (n = 9) and treatment-naive (n = 16) patients [...]

Mené sur 28 patients atteints d'une leucémie aiguë récidivante, réfractaire ou de pronostic défavorable, cet essai de phase I évalue la dose maximale tolérée de l'alvocidib en combinaison avec le vorinostat

A Phase I Trial of Vorinostat and Alvocidib in Patients with Relapsed, Refractory, or Poor Prognosis Acute Leukemia, or Refractory Anemia with Excess Blasts-2

Holkova, Beata ; Supko, Jeffrey G. ; Ames, Matthew M. ; Reid, Joel M. ; Shapiro, Geoffrey I. ; Perkins, Edward Brent ; Ramakrishnan, Viswanathan ; Tombes, Mary Beth ; Honeycutt, Connie ; McGovern, Renee M. ; Kmieciak, Maciej ; Shrader, Ellen ; Wellons, Martha D. ; Sankala, Heidi ; Doyle, Austin ; Wright, John ; Roberts, John D. ; Grant, Steven

Purpose: This phase I study was conducted to identify the maximum-tolerated dose (MTD) of alvocidib when combined with vorinostat in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Secondary objectives included investigating the pharmacokinetic and pharmacodynamic effects of the combination. Experimental Design: Patients received vorinostat (200 mg orally, three times a day, for 14 days) on a 21-day cycle, combined with 2 [...]

Menée sur 5 patients, cette étude évalue la faisabilité et l'efficacité d'une immunothérapie adoptive pour le traitement d’une leucémie lymphoblastique aiguë chimio-réfractaire à cellules B

CD19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia

Brentjens, Renier J. ; Davila, Marco L. ; Riviere, Isabelle ; Park, Jae ; Wang, Xiuyan ; Cowell, Lindsay G. ; Bartido, Shirley ; Stefanski, Jolanta ; Taylor, Clare ; Olszewska, Malgorzata ; Borquez-Ojeda, Oriana ; Qu, Jinrong ; Wasielewska, Teresa ; He, Qing ; Bernal, Yvette ; Rijo, Ivelise V. ; Hedvat, Cyrus ; Kobos, Rachel ; Curran, Kevin ; Steinherz, Peter ; Jurcic, Joseph ; Rosenblat, Todd ; Maslak, Peter ; Frattini, Mark ; Sadelain, Michel

Adults with relapsed B cell acute lymphoblastic leukemia (B-ALL) have a dismal prognosis. Only those patients able to achieve a second remission with no minimal residual disease (MRD) have a hope for long-term survival in the context of a subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We have treated five relapsed B-ALL subjects with autologous T cells expressing a CD19-specific CD28/CD3ζ second-generation dual-signaling chimeric antigen receptor (CAR) termed 19-28z. [...]

Cet article présente les données ayant servi de base à l'autorisation de mise sur le marché américain du vismodegib pour le traitement de patients ateints d'un carcinome basocellulaire métastatique ou localement avancé

U.S. Food and Drug Administration Approval: Vismodegib for Recurrent, Locally Advanced or Metastatic Basal Cell Carcinoma

Axelson, Michael ; Liu, Ke ; Jiang, Xiaoping ; He, Kun ; Wang, Jian ; Zhao, Hong ; Kufrin, Dubravka ; Palmby, Todd ; Dong, Zedong ; Russell, Anne M ; Pope Miksinski, Sarah ; Keegan, Patricia ; Pazdur, Richard

The data and regulatory considerations leading to FDA's January 30, 2012 approval of ErivedgeTM (vismodegib) capsules for the treatment of patients with recurrent, locally advanced or metastatic basal cell carcinoma (BCC) are described. FDA's approval decision was based primarily on the results observed in a single-arm, parallel-cohort, international trial of vismodegib, administered orally at 150 mg daily until disease progression, in patients with pathologically confirmed, recurrent, locally [...]

A partir d'une revue systématique de la littérature (22 essais prospectifs et 3 essais rétrospectifs identifiés), cette étude analyse l'efficacité de trois inhibiteurs de la topoisomérase I (irinotecan, etirinotecan et topotecan) pour le traitement d'un cancer métastatique du sein

A systematic review on topoisomerase 1 inhibition in the treatment of metastatic breast cancer

Kümler, Iben ; Brünner, Nils ; Stenvang, Jan ; Balslev, Eva ; Nielsen, DorteL

Following treatment with anthracyclines and taxanes, few established options exist for the treatment of metastatic breast cancer (MBC). Although the topoisomerase 1 inhibitors irinotecan, etirinotecan, and topotecan have been used in clinical trials on MBC, the drugs have never been introduced as standard treatment for the disease. We performed a systematic review on topoisomerase 1 inhibitors in MBC and found 22 prospective trials and three retrospective ones. No phase III trials were [...]

Mené sur 444 patientes atteintes d'un cancer métastatique du sein HER2+, cet essai de phase III évalue, du point de vue de la survie globale, le lapatinib en combinaison avec le paclitaxel

Randomized Trial of Lapatinib Versus Placebo Added to Paclitaxel in the Treatment of Human Epidermal Growth Factor Receptor 2–Overexpressing Metastatic Breast Cancer

Guan, Zhongzhen ; Xu, Binghe ; DeSilvio, Michelle L. ; Shen, Zhenzhou ; Arpornwirat, Wichit ; Tong, Zhongsheng ; Lorvidhaya, Vicharn ; Jiang, Zefei ; Yang, Junlan ; Makhson, Anatoly ; Leung, Wai Lim ; Russo, Mark W. ; Newstat, Beth ; Wang, Li ; Chen, George ; Oliva, Cristina ; Gomez, Henry

Purpose Lapatinib is an oral small-molecule tyrosine kinase inhibitor of both epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2). This study is designed to test whether the addition of lapatinib to paclitaxel improves overall survival (OS) compared with placebo plus paclitaxel in patients with HER2-overexpressing metastatic breast cancer (MBC). Patients And methods This phase III, randomized, double-blind study assessed the efficacy and safety of lapatinib plus [...]

A partir d'une revue de la littérature publiée jusqu'en septembre 2012 (13 études), cette méta-analyse évalue, du point de vue de la survie sans progression et de la survie globale, l'intérêt d'une radiothérapie adjuvante pour traiter un cancer gastrique résécable

Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

Ohri, Nitin ; Garg, Madhur K. ; Aparo, Santiago ; Kaubisch, Andreas ; Tome, Wolfgang ; Kennedy, Timothy J. ; Kalnicki, Shalom ; Guha, Chandan

Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for [...]

Menée in vitro et in vivo, cette étude montre que des inhibiteurs de la 12-lipoxygénase peuvent réduire la radiorésistance des cellules cancéreuses humaines de la prostate

Radiosensitivity of Human Prostate Cancer Cells can be Modulated by Inhibition of 12-Lipoxygenase

Lövey, J. ; Nie, D. ; Tóvári, J. ; Kenessey, I. ; Tímár, J. ; Kandouz, M. ; Honn, K. V.

Summary Nearly 30% of prostate cancer (PCa) patients treated with potentially curative doses relapse at the sites of irradiation. How some tumor cells acquire radioresistance is poorly understood. The platelet-type 12-lipoxygenases (12-LOX)-mediated arachidonic acid metabolism is important in PCa progression. Here we show that 12-LOX confers radioresistance upon PCa cells. Treatment with 12-LOX inhibitors baicalein or BMD122 sensitizes PCa cells to radiation, without radiosensitizing normal [...]

A partir d'une revue systématique de la littérature publiée jusqu'en août 2012 (4 études, 398 patients), cette méta-analyse évalue, par rapport à un traitement anti-androgénique différé, les avantages et les inconvénients d'un traitement anti-androgénique précoce chez les patients présentant un envahissement ganglionnaire après traitement local d'un cancer de la prostate

Early versus deferred androgen suppression therapy for patients with lymph node-positive prostate cancer after local therapy with curative intent: a systematic review

Kunath, Frank ; Keck, Bastian ; Rucker, Gerta ; Motschall, Edith ; Wullich, Bernd ; Antes, Gerd ; Meerpohl, Joerg

BACKGROUND:There is currently no consensus regarding the optimal timing for androgen suppression therapy in patients with prostate cancer that have undergone local therapy with curative intent but are proven to have node-positive disease without signs of distant metastases at the time of local therapy. The objective of this systematic review was to determine the benefits and harms of early (at the time of local therapy) versus deferred (at the time of clinical disease progression) androgen [...]

Menée sur 50 patients atteints d'un cancer primitif du rectum de stade IV et présentant des métastases pulmonaires et/ou hépatiques, cette étude évalue l'efficacité, du point de vue du taux de récidive et de la survie globale à 2 ans, et la tolérabilité d'une radiothérapie pré-opératoire de courte durée suivie, après traitement chirurgical radical des sites tumoraux, par une chimiothérapie à base de capécitabine et d'oxaliplatine en combinaison avec le bevacizumab

Evaluation of short-course radiotherapy followed by neoadjuvant bevacizumab, capecitabine, and oxaliplatin and subsequent radical surgical treatment in primary stage IV rectal cancer

van Dijk, T. H. ; Tamas, K. ; Beukema, J. C. ; Beets, G. L. ; Gelderblom, A. J. ; de Jong, K. P. ; Nagtegaal, I. D. ; Rutten, H. J. ; van de Velde, C. J. ; Wiggers, T. ; Hospers, G. A. ; Havenga, K.

Background To evaluate the efficacy and tolerability of preoperative short-course radiotherapy followed by capecitabine and oxaliplatin treatment in combination with bevacizumab and subsequent radical surgical treatment of all tumor sites in patients with stage IV rectal cancer.Patients and methods Adults with primary metastasized rectal cancer were enrolled. They received radiotherapy (5 × 5 Gy) followed by bevacizumab (7.5 mg/kg, day 1) and oxaliplatin (130 mg/m2, day 1) intravenously and [...]

Menée sur 1 135 patientes atteintes d'un cancer invasif du sein avec pronostic favorable, cette étude évalue, du point de vue de la survie spécifique, l'intérêt d'une radiothérapie adjuvante ou du tamoxifène après un traitement chirurgical conservateur

Radiotherapy or tamoxifen after conserving surgery for breast cancers of excellent prognosis: British Association of Surgical Oncology (BASO) II trial

Blamey, R. W. ; Bates, T. ; Chetty, U. ; Duffy, S. W. ; Ellis, I. O. ; George, D. ; Mallon, E. ; Mitchell, M. J. ; Monypenny, I. ; Morgan, D. A. L. ; Macmillan, R. D. ; Patnick, J. ; Pinder, S. E.

Background : The incidence of local recurrence (LR) after conservative surgery for early breast cancer without adjuvant therapy is unacceptably high even with favourable tumours. The aim of this study was to examine the effect of adjuvant therapies in tumours with excellent prognostic features. Methods : Patients with primary invasive breast cancer <2 cm diameter, grade 1 or good prognosis special type, and node negative, treated by wide local excision (WLE) with clear margins were randomised [...]

A partir de données médicales portant sur 554 adultes atteints d'un glioblastome, cette étude montre qu'un traitement combinant l'acide valproïque, un antiépileptique, et une radiothérapie améliore la survie globale des patients

Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival

Barker, Christopher A. ; Bishop, Andrew J. ; Chang, Maria ; Beal, Kathryn ; Chan, Timothy A.

Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS). Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning [...]

A partir d'une compilation des molécules qui, après une autorisation de mise sur le marché, ont démontré une toxicité dans leur mise en oeuvre en pratique clinique, cet article analyse les risques associés à l'usage de critères de jugement de substitution dans les essais

Surrogate outcomes in clinical trials: A cautionary tale

Svensson S, Menkes D. B. Lexchin J.

To illustrate the perils of relying on surrogates, we compiled a table of drugs, approved on the basis of surrogate outcome data, which after adoption into practice were shown to be harmful through clinical trials or meta-analyses (eTable).

Menée par questionnaires auprès de 486 patients atteints de cancer, cette étude analyse leurs attitudes relatives à la participation à un essai clinique randomisé

Drivers and barriers to patient participation in RCTs

Jenkins, V. ; Farewell, V. ; Farewell, D. ; Darmanin, J. ; Wagstaff, J. ; Langridge, C. ; Fallowfield, L.

Background: Recruitment of patients into randomised clinical trials (RCTs) is essential for treatment evaluation. Appreciation of the barriers and drivers towards participation is important for trial design, communication and information provision. Method: As part of an intervention to facilitate effective multidisciplinary team communication about RCTs, cancer patients completed two study-specific questionnaires following trial discussions. One questionnaire examined reasons why patients [...]

Cet article décrit les méthodes disponibles, notamment les schémas adaptatifs, pour les essais de phase I d'évaluation de deux agents anticancéreux en combinaison

Adaptive designs for dual-agent phase I dose-escalation studies

Harrington, Jennifer A. ; Wheeler, Graham M. ; Sweeting, Michael J. ; Mander, Adrian P. ; Jodrell, Duncan I.

Anticancer agents used in combination are fundamental to successful cancer treatment, particularly in a curative setting. For dual-agent phase I trials, the goal is to identify drug doses and schedules for further clinical testing. However, current methods for establishing the recommended phase II dose for agents in combination can fail to fully explore drug interactions. With increasing numbers of anticancer drugs requiring testing, new adaptive model-based trial designs that improve on [...]

Cet article passe en revue les travaux récents sur le diagnostic et le traitement des leucémies lymphoblastiques aiguës

Acute lymphoblastic leukaemia

Inaba, Hiroto ; Greaves, Mel ; Mullighan, Charles G.

Acute lymphoblastic leukaemia occurs in both children and adults but its incidence peaks between 2 and 5 years of age. Causation is multifactorial and exogenous or endogenous exposures, genetic susceptibility, and chance have roles. Survival in paediatric acute lymphoblastic leukaemia has improved to roughly 90% in trials with risk stratification by biological features of leukaemic cells and response to treatment, treatment modification based on patients' pharmacodynamics and pharmacogenomics, [...]