Mené sur 1 334 patientes atteintes d'un cancer du sein traité par mastectomie (âge : inférieur à 75 ans ; durée médiane de suivi : 11,3 ans), cet essai multicentrique de phase III évalue, en fonction de la localisation de la tumeur, du statut des ganglions lymphatiques axillaires et du traitement adjuvant reçu, l'intérêt d'une radiothérapie des ganglions mammaires internes pour améliorer la survie globale à 10 ans

Ten-Year Survival Results of a Randomized Trial of Irradiation of Internal Mammary Nodes After Mastectomy

Hennequin, Christophe ; Bossard, Nadine ; Servagi-Vernat, Stéphanie ; Maingon, Philippe ; Dubois, Jean-Bernard ; Datchary, Jean ; Carrie, Christian ; Roullet, Bernard ; Suchaud, Jean-Philippe ; Teissier, Eric ; Lucardi, Audrey ; Gérard, Jean-Pierre ; Belot, Aurélien ; Iwaz, Jean ; Ecochard, René ; Romestaing, Pascale

To evaluate the efficacy of irradiation of internal mammary nodes (IMN) on 10-year overall survival in breast cancer patients after mastectomy. This multicenter phase 3 study enrolled patients with positive axillary nodes (pN+) or central/medial tumors with or without pN+. Other inclusion criteria were age <75 and a Karnofsky index ≥70. All patients received postoperative irradiation of the chest wall and supraclavicular nodes and were randomly assigned to receive IMN irradiation or not. [...]

Cet article passe en revue les travaux récents sur les mécanismes moléculaires liés aux thérapies ciblées à base de petites molécules inhibant des protéines kinases

The molecular basis of targeting protein kinases in cancer therapeutics

Tsai, Chung-Jung ; Nussinov, Ruth

In this paper, we provide an overview of targeted anticancer therapies with small molecule kinase inhibitors. First, we discuss why a single constitutively active kinase emanating from a variety of aberrant genetic alterations is capable of transforming a normal cell, leading it to acquire the hallmarks of a cancer cell. To draw attention to the fact that kinase inhibition in targeted cancer therapeutics differs from conventional cytotoxic chemotherapy, we exploit a conceptual framework [...]

Menée à l'aide d'un modèle murin, cette étude met en évidence un mécanisme par lequel, en provoquant une lésion des nerfs dans la moelle osseuse, le cisplatine perturbe la régénération hématopoïétique

Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration

Lucas, Daniel ; Scheiermann, Christoph ; Chow, Andrew ; Kunisaki, Yuya ; Bruns, Ingmar ; Barrick, Colleen ; Tessarollo, Lino ; Frenette, Paul S.

Anticancer chemotherapy drugs challenge hematopoietic tissues to regenerate but commonly produce long-term sequelae. Chemotherapy-induced deficits in hematopoietic stem or stromal cell function have been described, but the mechanisms mediating hematopoietic dysfunction remain unclear. Administration of multiple cycles of cisplatin chemotherapy causes substantial sensory neuropathy. Here we demonstrate that chemotherapy-induced nerve injury in the bone marrow of mice is a crucial lesion [...]

A partir des travaux récents sur les leucémies avec réarrangements MLL, cet article passe en revue les perspectives offertes par les connaissances sur des mécanismes épigénétiques pour développer des traitements anticancéreux

Recent progress toward epigenetic therapies: the example of mixed lineage leukemia

Neff, Tobias ; Armstrong, Scott A.

The importance of epigenetic gene regulatory mechanisms in normal and cancer development is increasingly evident. Genome-wide analyses have revealed the mutation, deletion and dysregulated expression of chromatin-modifying enzymes in a number of cancers, including hematologic malignancies. Genome-wide studies of DNA-methylation and histone modifications are beginning to reveal the landscape of cancer-specific chromatin patterns. In parallel, recent genetic loss-of-function studies in murine [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en régulant le micro-ARN let-7a, CXCR4 induit une résistance aux chimiothérapies dans les cellules de leucémie myéloïde aiguë

CXCR4 downregulation of let-7a drives chemoresistance in acute myeloid leukemia

Chen, Ye ; Jacamo, Rodrigo ; Konopleva, Marina ; Garzon, Ramiro ; Croce, Carlo ; Andreeff, Michael

We examined the role of microRNAs (miRNAs) in targeting the stromal-derived factor 1α/CXCR4 (SDF-1α/CXCR4) axis to overcome chemoresistance of AML cells. Microarray analysis of OCI-AML3 cells revealed that the miRNA let-7a was downregulated by SDF-1α–mediated CXCR4 activation and increased by CXCR4 inhibition. Overexpression of let-7a in AML cell lines was associated with decreased c-Myc and BCL-XL protein expression and enhanced chemosensitivity, both in vitro and in vivo. We identified the [...]

Menée à l'aide d'une xénogreffe orthotopique de cancer du poumon humain non à petites cellules, cette étude montre que le phospho-sulindac administré sous forme d'aérosol peut inhiber la tumorigenèse

Aerosol administration of phospho-sulindac inhibits lung tumorigenesis

Cheng, Ka Wing ; Wong, Chi C ; Alston, Ninche ; Mackenzie, Gerardo G ; Huang, Liqun ; Ouyang, Nengtai ; Xie, Gang ; Wiedmann, Timothy ; Rigas, Basil

Phospho-sulindac (PS) is a sulindac derivative with promising anticancer activity in lung cancer, but its limited metabolic stability presents a major challenge for systemic therapy. We reasoned that inhalation delivery of PS might overcome first-pass metabolism and produce high levels of intact drug in lung tumors. Here, we developed a system for aerosolization of PS and evaluated the antitumor efficacy of inhaled PS in an orthotopic model of human non-small cell lung cancer (A549 cells). We [...]

Menée sur des lignées cellulaires, cette étude suggère l'intérêt de combiner bortezomib et interféron gamma pour le traitement d'un carcinome à cellules rénales de stade métastatique

NF-κB Inhibition by Bortezomib Permits Interferon-γ-Activated RIP1 Kinase-Dependent Necrosis in Renal Cell Carcinoma

Thapa, Roshan J ; Chen, Peirong ; Cheung, Mitchell ; Nogusa, Shoko ; Pei, Jianming ; Peri, Suraj ; Testa, Joseph R ; Balachandran, Siddharth

Advanced renal cell carcinoma (RCC) is an invariably fatal cancer. Currently, small-molecule inhibitors that target cell-growth, angiogenesis, or nutrient-sensing pathways represent the primary pharmacological interventions for this disease, but these inhibitors only delay tumor progression and are not curative. The cytokine interferon (IFN)-γ showed the potential to provide lasting remission in several phase I/II trials for advanced RCC, but subsequent trials, including a multi-center phase [...]

Menée in vitro et à l'aide de xénogreffes, cette étude met en évidence le rôle joué par une surexpression des kinases RSK3 ou RSK4 dans les mécanismes de résistance à un traitement par inhibiteur de PI3K

RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer

Serra, Violeta ; Eichhorn, Pieter J. A. ; Garc, ; xEd, ; a, Garc ; a, Celina ; Ibrahim, Yasir H. ; Prudkin, Ludmila ; xE, ; nchez, Gertrudis ; Rodr, ; guez, Olga ; Ant, ; xF, ; n, Pilar ; Parra, Josep-Llu ; Marlow, Sara ; Scaltriti, Maurizio ; rez-Garcia, Jos ; Prat, Aleix ; Arribas, Joaqu ; Hahn, William C. ; Kim, So Young ; Baselga, Jos

The PI3K signaling pathway regulates diverse cellular processes, including proliferation, survival, and metabolism, and is aberrantly activated in human cancer. As such, numerous compounds targeting the PI3K pathway are currently being clinically evaluated for the treatment of cancer, and several have shown some early indications of efficacy in breast cancer. However, resistance against these agents, both de novo and acquired, may ultimately limit the efficacy of these compounds. Here, we have [...]

Cet article passe en revue les travaux récents sur le développement d'inhibiteurs des voies PI3K/AKT/mTOR et Raf/MEK/ERK pour le traitement d'un cancer du sein

Targeting the PI3K/AKT/mTOR and Raf/MEK/ERK pathways in the treatment of breast cancer

Saini, Kamal S. ; Loi, Sherene ; de Azambuja, Evandro ; Metzger-Filho, Otto ; Saini, Monika Lamba ; Ignatiadis, Michail ; Dancey, Janet E. ; Piccart-Gebhart, Martine J.

Alterations of signal transduction pathways leading to uncontrolled cellular proliferation, survival, invasion, and metastases are hallmarks of the carcinogenic process. The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) and the Raf/mitogen-activated and extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways are critical for normal human physiology, and also commonly dysregulated in several human cancers, [...]

Cet article passe en revue les travaux récents sur les taxanes en traitement adjuvant d'un cancer du sein et suggère l'intérêt de ces molécules pour les patientes atteintes d'une tumeur ER+ de bas grade

Taxane benefit in breast cancer - a role for grade and chromosomal stability

A'Hern, Roger P. ; Jamal-Hanjani, Mariam ; Szasz, A. Marcell ; Johnston, Stephen R. D. ; Reis-Filho, Jorge S. ; Roylance, Rebecca ; Swanton, Charles

Chromosomal instability, which is a characteristic of many human cancers, contributes to intratumour heterogeneity and has been functionally implicated in resistance to taxane therapy in tumour models. However, defining the status of tumour chromosomal instability in a given tumour to test this hypothesis remains challenging. Measurements of numerical and structural chromosomal heterogeneity demonstrate that histological grade correlates with chromosomal instability in oestrogen receptor [...]

Menée à l'aide d'un modèle murin de gliome, cette étude évalue l'activité antitumorale d'un traitement à base de cellules souches neurales et de 5-fluorocytosine

Neural Stem Cell–Mediated Enzyme/Prodrug Therapy for Glioma: Preclinical Studies

Aboody, Karen S. ; Najbauer, Joseph ; Metz, Marianne Z. ; D’Apuzzo, Massimo ; Gutova, Margarita ; Annala, Alexander J. ; Synold, Timothy W. ; Couture, Larry A. ; Blanchard, Suzette ; Moats, Rex A. ; Garcia, Elizabeth ; Aramburo, Soraya ; Valenzuela, Valerie V. ; Frank, Richard T. ; Barish, Michael E. ; Brown, Christine E. ; Kim, Seung U. ; Badie, Behnam ; Portnow, Jana

High-grade gliomas are extremely difficult to treat because they are invasive and therefore not curable by surgical resection; the toxicity of current chemo- and radiation therapies limits the doses that can be used. Neural stem cells (NSCs) have inherent tumor-tropic properties that enable their use as delivery vehicles to target enzyme/prodrug therapy selectively to tumors. We used a cytosine deaminase (CD)–expressing clonal human NSC line, HB1.F3.CD, to home to gliomas in mice and locally [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude évalue l'activité antitumorale d'un anticorps monoclonal ciblé sur le récepteur FGFR3 pour le traitement d'un cancer de la vessie

Fibroblast Growth Factor Receptor 3 is a Rational Therapeutic Target in Bladder Cancer

Gust, Kilian M ; McConkey, David J ; Awrey, Shannon ; Hegarty, Paul K ; Qing, Jing ; Bondaruk, Jolanta ; Ashkenazi, Avi ; Czerniak, Bogdan ; Dinney, Colin P ; Black, Peter C

Activating mutations of Fibroblast growth factor receptor-3 (FGFR3) have been described in approximately 75% of low-grade papillary bladder tumors. In muscle invasive disease, FGFR3 mutations are found in 20% of tumors, but overexpression of FGFR3 is observed in about half of cases. Therefore, FGFR3 is a particularly promising target for therapy in bladder cancer. Up to now most drugs tested for inhibition of FGFR3 have been small molecule, multi-tyrosine kinase inhibitors. More recently, a [...]

Mené sur 15 patients pédiatriques atteints d'une tumeur solide réfractaire aux traitements existants, cet essai de phase I évalue la toxicité et l'activité antitumorale du ridaforolimus, un inhibiteur de mTOR

A Multicenter, First-in-Pediatrics, Phase 1, Pharmacokinetic and Pharmacodynamic Study of Ridaforolimus in Patients with Refractory Solid Tumors

Gore, Lia ; Trippett, Tanya M ; Katzenstein, Howard ; Boklan, Jessica ; Narendran, Aru ; Smith, Amy ; Macy, Margaret E ; Rolla, Katherine ; Narasimhan, Narayana I ; Squillace, Rachel M ; Turner, Christopher D ; Haluska, Frank G ; Nieder, Michael

Purpose: Ridaforolimus (MK-8669, AP23573) is a potent and selective mTOR inhibitor. Preclinically, ridaforolimus displays antiproliferative activity against a variety of human tumors in vitro and tumor xenograft models in vivo, with additive or synergistic activity when combined with other anticancer agents. Anti-tumor activity has been confirmed in adults. This phase I study determined the safety, pharmacological, biologic, and toxicity profiles of ridaforolimus in pediatric patients with [...]

Mené sur 66 patients atteints d'un lymphome non hodgkinien à cellules B ou d'un myélome multiple ou d'une maladie de Castleman, cet essai de phase I évalue la toxicité et l'activité antitumorale du siltuximab, un anticorps monoclonal chimérique anti IL-6

A Phase I, Open-Label Study of Siltuximab, an Anti-IL-6 Monoclonal Antibody, in Patients with B-Cell Non-Hodgkin's Lymphoma, Multiple Myeloma, or Castleman's Disease

Kurzrock, Razelle ; Voorhees, Peter M. ; Casper, Corey ; Furman, Richard R. ; Fayad, Luis ; Lonial, Sagar ; Borghaei, Hossein ; Jagannath, Sundar ; Sokol, Lubomir ; Usmani, Saad ; van de Velde, Helgi ; Qin, Xiang ; Puchalski, Thomas A. ; Hall, Brett ; Reddy, Manjula ; Qi, Ming ; Van Rhee, Frits

Purpose: To evaluate the safety and pharmacokinetics of siltuximab, an anti-interleukin-6 chimeric mAb in patients with B-cell non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), or Castleman's disease (CD). Experimental Design: In an open-label, dose-finding, seven-cohort, phase I study, patients with NHL, MM, or symptomatic CD received siltuximab 3, 6, 9, or 12 mg/kg qw, q2w, or q3w. Response was assessed in all disease types. Clinical benefit response (CBR: composite of hemoglobin, fatigue, [...]

Mené sur 17 patients atteints d'un mélanome de stade IV et 4 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue la toxicité et l'activité antitumorale d'un traitement combinant le tremelimumab et un composé appelé PF-3512676, un agoniste du récepteur TLR-9

Phase I study of tremelimumab (CP-675 206) plus PF-3512676 (CPG 7909) in patients with melanoma or advanced solid tumours

Millward, M. ; Underhill, C. ; Lobb, S. ; McBurnie, J. ; Meech, S. J. ; Gomez-Navarro, J. ; Marshall, M. A. ; Huang, B. ; Mather, C. B.

Background: Tremelimumab, a fully human cytotoxic T-lymphocyte antigen 4 monoclonal antibody, and PF-3512676, a Toll-like receptor-9 agonist, are targeted immune modulators that elicit durable single-agent antitumour activity in advanced cancer. Methods: To determine the maximum tolerated dose (MTD) of these agents combined during this phase I study, patients received intravenous tremelimumab (6.0, 10.0, or 15.0 mg kg−1) every 12 weeks plus subcutaneous PF-3512676 (0.05, 0.10, or 0.15 mg kg−1) [...]

Mené en Grèce sur 332 patients atteints d'un cancer métastatique du poumon non à petites cellules, cet essai de phase III compare, du point de vue de la durée avant progression de la tumeur, le pemetrexed et l'erlotinib en traitement de deuxième ou troisième ligne

Pemetrexed versus erlotinib in pretreated patients with advanced non–small cell lung cancer: A Hellenic Oncology Research Group (HORG) randomized phase 3 study

Karampeazis, Athanasios ; Voutsina, Alexandra ; Souglakos, John ; Kentepozidis, Nikos ; Giassas, Stelios ; Christofillakis, Charalambos ; Kotsakis, Athanasios ; Papakotoulas, Pavlos ; Rapti, Ageliki ; Agelidou, Maria ; Agelaki, Sofia ; Vamvakas, Lambros ; Samonis, George ; Mavroudis, Dimitris ; Georgoulias, Vassilis

BACKGROUND In this superiority study, pemetrexed was compared with erlotinib in pre-treated patients with metastatic non–small cell lung cancer (NSCLC). METHODS Patients with stage IIIB/IV NSCLC who progressed after first-line or second-line treatment were randomized to receive either pemetrexed or erlotinib. In total, 21.7% of patients in the pemetrexed arm and 23.5% of patients in the erlotinib arm had squamous cell histology, and treatment was third line in 39.2% and 46.4% of patients, [...]

Mené sur 130 patientes atteintes d'un cancer du sein ER+ de stade avancé après la ménopause, cet essai de phase II évalue, du point de vue de la survie sans progression, l'ajout d'un inhibiteur d'histone désacétylase, l'entinostat, à un inhibiteur d'aromatase, l'exémestane

Randomized Phase II, Double-Blind, Placebo-Controlled Study of Exemestane With or Without Entinostat in Postmenopausal Women With Locally Recurrent or Metastatic Estrogen Receptor-Positive Breast Cancer Progressing on Treatment With a Nonsteroidal Aromatase Inhibitor

Yardley, Denise A. ; Ismail-Khan, Roohi R. ; Melichar, Bohuslav ; Lichinitser, Mikhail ; Munster, Pamela N. ; Klein, Pamela M. ; Cruickshank, Scott ; Miller, Kathy D. ; Lee, Min J. ; Trepel, Jane B.

Purpose Entinostat is an oral isoform selective histone deacetylase inhibitor that targets resistance to hormonal therapies in estrogen receptor–positive (ER+) breast cancer. This randomized, placebo-controlled, phase II study evaluated entinostat combined with the aromatase inhibitor exemestane versus exemestane alone. Patients and Methods Postmenopausal women with ER+ advanced breast cancer progressing on a nonsteroidal aromatase inhibitor were randomly assigned to exemestane 25 mg daily plus [...]

Menée sur des lignées cellulaires, à l'aide de xénogreffes et sur 81 patientes atteintes d'un cancer du sein présentant une amplication d'un récepteur du facteur de croissance des fibroblastes, cette étude évalue l'activité antitumorale du dovitinib, un inhibiteur de FGFR1, FGFR2 et FGFR3

Targeting FGFR With Dovitinib (TKI258): Preclinical and Clinical Data in Breast Cancer

Andre, Fabrice ; Bachelot, Thomas ; Campone, Mario ; Dalenc, Florence ; Perez-Garcia, Jose ; Hurvitz, Sara A ; Turner, Nicholas C. ; Rugo, Hope ; Smith, John W. ; Deudon, Stephanie ; Shi, Michael M. ; Zhang, Yong ; Kay, Andrea ; Graus Porta, Diana ; Yovine, Alejandro ; Baselga, Jose

Purpose: Fibroblast growth factor receptor 1 (FGFR1) and FGFR2 amplifications are observed in approximately 10% of breast cancers and are related to poor outcomes. We evaluated whether dovitinib (TKI258), an inhibitor of FGFR1, FGFR2, and FGFR3, presented antitumor activity in FGFR-amplified breast cancers. Experimental Design: Preclinical activity of dovitinib was evaluated in breast cancer cell lines and an FGFR1-amplified xenograft model (HBCx2). Dovitinib was then evaluated in a phase II [...]

Cet article passe en revue les travaux récents sur l'intérêt du trastuzumab pour les patientes âgées atteintes d'un cancer du sein HER2+ et pour les patientes présentant des tumeurs de faible volume

Trastuzumab in small tumours and in elderly women

Albanell, Joan ; Ciruelos, Eva M. ; Lluch, Ana ; Muñoz, Montserrat ; Rodríguez, César A.

Results of trials assessing the role of trastuzumab in the adjuvant setting in early breast cancer have brought a new standard of treatment to clinical practice. Nevertheless, some groups of patients are underrepresented in these trials and thus therapy should be planned based on incomplete information or lack of solid data. Two of these groups are high-risk HER2+ small tumours (<1cm) and elderly patients. In this review we aimed at addressing the most relevant data about these two populations [...]

Cet article fait le point sur l'efficacité de différentes modalités de radiothérapie, combinée ou non à une hormonothérapie, pour traiter un cancer de la prostate à risque élevé de récidive

Management of high-risk prostate cancer: Radiation therapy and hormonal therapy

Nomiya, Takuma ; Tsuji, Hiroshi ; Toyama, Shingo ; Maruyama, Katsuya ; Nemoto, Kenji ; Tsujii, Hirohiko ; Kamada, Tadashi

The prognosis of high-risk prostate cancer is poor with a high mortality rate. The Radiation Therapy Oncology Group (RTOG) has performed dose-escalation studies of external beam radiation therapy (EBRT) and has developed high-precision radiation therapy (RT) methods such as intensity-modulated RT, carbon ion therapy, and proton beam therapy. High-dose rate brachytherapy (HDR-BT) is also studied as an option for high-risk prostate cancer treatment. Past clinical trials have suggested that the [...]

Mené au Japon sur 134 patientes atteintes d'un carcinome épidermoïde du col utérin de stade IB2, IIA2 ou IIB, cet essai randomisé de phase III évalue l'intérêt d'ajouter une chimiothérapie néoadjuvante de type BOMP (bléomycine, vindésine, mitomycine, cisplatine) à une chirurgie radicale pour améliorer la survie globale des patientes

Phase III randomised controlled trial of neoadjuvant chemotherapy plus radical surgery vs radical surgery alone for stages IB2, IIA2, and IIB cervical cancer: a Japan Clinical Oncology Group trial (JCOG 0102)

Katsumata, N. ; Yoshikawa, H. ; Kobayashi, H. ; Saito, T. ; Kuzuya, K. ; Nakanishi, T. ; Yasugi, T. ; Yaegashi, N. ; Yokota, H. ; Kodama, S. ; Mizunoe, T. ; Hiura, M. ; Kasamatsu, T. ; Shibata, T. ; Kamura, T.

Background : A phase III trial was conducted to determine whether neoadjuvant chemotherapy (NACT) before radical surgery (RS) improves overall survival. Methods : Patients with stage IB2, IIA2, or IIB squamous cell carcinoma of the uterine cervix were randomly assigned to receive either BOMP (bleomycin 7 mg days 1–5, vincristine 0.7 mg m−2 day 5, mitomycin 7mgm−2 day 5, cisplatin 14mgm−2 days 1–5, every 3 weeks for 2 to 4 cycles) plus RS (NACT group) or RS alone (RS group). Patients with [...]

Mené sur 115 patients traités entre 2001 et 2003 pour un carcinome rhinopharyngé non kératinisant ou indifférencié de stade loco-régionalement avancé (durée médiane de suivi : 114 mois), cet essai de phase III évalue, du point de vue du taux de survie sans métastase, du taux de survie globale à 5 ans et de la toxicité, l'intérêt d'ajouter à une radiothérapie une chimiothérapie concomitante hebdomadaire à base d'oxaliplatine

Long-term follow-up of a phase III study comparing radiotherapy with or without weekly oxaliplatin for locoregionally advanced nasopharyngeal carcinoma

Wu, X. ; Huang, P. Y. ; Peng, P. J. ; Lu, L. X. ; Han, F. ; Wu, S. X. ; Hou, X. ; Zhao, H. Y. ; Huang, Y. ; Fang, W. F. ; Zhao, Y. Y. ; Xue, C. ; Hu, Z. H. ; Zhang, J. ; Zhang, J. W. ; Ma, Y. X. ; Liang, W. H. ; Zhao, C. ; Zhang, L.

Background : Previous results from our trial showed that adding oxaliplatin to radiotherapy (RT) increased survival in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term efficacy and late toxic effects. Patients and methods : Between January 2001 and January 2003, 115 Patients with nonkeratinizing/undifferentiated locoregionally advanced NPC were randomly to receive either RT alone (n = 56) or plus concurrent oxaliplatin 70 [...]

Cet article résume les conclusions d'un workshop organisé par le National Cancer Institute autour des enjeux et perspectives des recherches sur l'efficacité comparative des thérapies ciblées des cancers

Comparative Effectiveness Research in Cancer Genomics and Precision Medicine: Current Landscape and Future Prospects

Simonds, Naoko I. ; Khoury, Muin J. ; Schully, Sheri D. ; Armstrong, Katrina ; Cohn, Wendy F. ; Fenstermacher, David A. ; Ginsburg, Geoffrey S. ; Goddard, Katrina A.B. ; Knaus, William A. ; Lyman, Gary H. ; Ramsey, Scott D. ; Xu, Jianfeng ; Freedman, Andrew N.

A major promise of genomic research is information that can transform health care and public health through earlier diagnosis, more effective prevention and treatment of disease, and avoidance of drug side effects. Although there is interest in the early adoption of emerging genomic applications in cancer prevention and treatment, there are substantial evidence gaps that are further compounded by the difficulties of designing adequately powered studies to generate this evidence, thus limiting [...]

Menée sur la période 2002-2012, cet article analyse l'évolution des différents critères de jugement utilisés pour l'autorisation accélérée de mise sur le marché des médicaments anticancéreux aux Etats-Unis

Use of Multiple Endpoints and Approval Paths Depicts a Decade of FDA Oncology Drug Approvals

Shea, Michael B ; Roberts, Samantha A ; Walrath, Jessica C ; Allen, Jeffrey ; Sigal, Ellen V

This study explores the historic use of different endpoints to support regular and accelerated approval of cancer drugs between 2002 and 2012. In the past ten years, two thirds of oncology regular approvals were based on endpoints other than overall survival. Over three quarters of accelerated approvals were based on response rates. The accelerated approval program has been heavily utilized over this time period, with one third of all approved oncology indications receiving accelerated [...]

Cet article analyse les enjeux éthiques des réformes visant à améliorer l’efficacité des essais cliniques de phase II

Ethics, Error, and Initial Trials of Efficacy

Hey, Spencer Phillips ; Kimmelman, Jonathan

Clinical trial reforms aimed at boosting phase 2 positive predictivity may involve ethical and social trade-offs.

Cet article passe en revue les perspectives offertes par les partenariats public-privé pour le développement de nouveaux traitements des rhabdomyosarcomes

Proof-of-concept rare cancers in drug development: the case for rhabdomyosarcoma

Sokolowski, E. ; Turina, C. B. ; Kikuchi, K. ; Langenau, D. M. ; Keller, C.

Rare diseases typically affect fewer than 200 000 patients annually, yet because thousands of rare diseases exist, the cumulative impact is millions of patients worldwide. Every form of childhood cancer qualifies as a rare disease—including the childhood muscle cancer, rhabdomyosarcoma (RMS). The next few years promise to be an exceptionally good era of opportunity for public–private collaboration for rare and childhood cancers. Not only do certain governmental regulation advantages exist, but [...]

Cet article présente les recommandations d'un groupe d'experts européens pour la prise en charge des cancers métastatiques du sein

International guidelines for management of metastatic breast cancer (MBC) from the European School of Oncology (ESO)–MBC Task Force: Surveillance, staging, and evaluation of patients with early-stage and metastatic breast cancer

Lin, Nancy U. ; Thomssen, Christoph ; Cardoso, Fatima ; Cameron, David ; Cufer, Tanja ; Fallowfield, Lesley ; Francis, Prudence A. ; Kyriakides, Stella ; Pagani, Olivia ; Senkus, Elzbieta ; Costa, Alberto ; Winer, Eric P.

In clinical practice, the surveillance and follow-up of patients with breast cancer (BC) is quite variable. At the 7th European Breast Cancer Conference, the ESO-MBC Task Force convened a series of lectures, followed by open debate, on the use of physical examination, imaging, and laboratory tests in patients with early-stage BC, and for restaging evaluations and follow-up among patients with MBC. Based on the available data, the Task Force recommends against intensive, routine radiologic or [...]