Menée sur 22 patients pédiatriques présentant des métastases pulmonaires, cette étude évalue, du point de vue de la dosimétrie et de la toxicité, l'intérêt d'une radiothérapie du poumon entier avec modulation d'intensité et préservation du coeur

Cardiac-Sparing Whole Lung IMRT in Children With Lung Metastasis

Kalapurakal, John A. ; Zhang, Yunkai ; Kepka, Alan ; Zawislak, Brian ; Sathiaseelan, Vythialingam ; Rigsby, Cynthia ; Gopalakrishnan, Mahesh

To demonstrate the dosimetric advantages of cardiac-sparing (CS) intensity modulated radiation therapy (IMRT) in children undergoing whole lung irradiation (WLI). Chest CT scans of 22 children who underwent simulation with 3-dimensional (n=10) or 4-dimensional (n=12) techniques were used for this study. Treatment planning was performed using standard anteroposterior-posteroanterior (S-RT) technique and CS-IMRT. Left and right flank fields were added to WLI fields to determine whether CS-IMRT [...]

Menée sur une lignée cellulaire de cancer du poumon non à petites cellules et à l'aide d'une xénogreffe, cette étude montre que des nanoparticules polymères contenant des taxanes peuvent augmenter l'efficacité d'une chimioradiothérapie

Polymeric Nanoparticles Containing Taxanes Enhance Chemoradiotherapeutic Efficacy in Non-small Cell Lung Cancer

Jung, Joohee ; Park, Sung-Jin ; Chung, Hye Kyung ; Kang, Hye-Won ; Lee, Sa-Won ; Seo, Min Hyo ; Park, Heon Joo ; Song, Si Yeol ; Jeong, Seong-Yun ; Choi, Eun Kyung

To reduce the side effects and improve the efficacy of chemoradiation therapy, taxanes were incorporated into polymeric nanoparticles (PNP), and their synergic effect on radiation therapy in non-small cell lung cancer was evaluated. The properties of PNP-taxanes were characterized by transmission electron microscopy and dynamic light scattering. The chemoradiotherapeutic efficacy of PNP-taxanes was determined by clonogenic assay, cellular morphology, and flow cytometry in A549 cells. In mice [...]

A partir des données administratives portant sur 58 patients atteints d'un lymphome cutané à cellules T traité entre 1991 et 2011 (durée moyenne de suivi : 41,3 mois), cette étude rétrospective évalue, du point de vue de la réponse complète, de la survie globale et du rapport coût-efficacité, l'intérêt d'une radiothérapie palliative à fraction unique

Outcome of Patients Treated With a Single-Fraction Dose of Palliative Radiation for Cutaneous T-Cell Lymphoma

Thomas, Tarita O. ; Agrawal, Priya ; Guitart, Joan ; Rosen, Steven T. ; Rademaker, Alfred W. ; Querfeld, Christiane ; Hayes, John P. ; Kuzel, Timothy M. ; Mittal, Bharat B.

Cutaneous T-cell lymphoma (CTCL) is a radiosensitive tumor. Presently, treatment with radiation is given in multiple fractions. The current literature lacks data that support single-fraction treatment for CTCL. This retrospective review assesses the clinical response in patients treated with a single fraction of radiation. This study reviewed the records of 58 patients with CTCL, primarily mycosis fungoides, treated with a single fraction of palliative radiation therapy (RT) between October [...]

Cet article passe en revue les études récentes concernant la prise en charge des lymphomes hodgkiniens de stade précoce et analyse le rôle de la radiothérapie dans le traitement de la maladie

Point/counterpoint: early stage Hodgkin lymphoma: the role of radiation therapy

Meyer, Ralph M. ; Hoppe, Richard T.

The results of recent clinical trials for the management of limited stage Hodgkin lymphoma have led to considerable debate, especially regarding the role of radiation therapy. This review highlights those recent trials and provides perspectives regarding their interpretation from a radiation oncologist and a hematologist.

Menée sur 36 patients présentant une récidive locale isolée d'un cancer du pancréas, cette étude rétrospective évalue, du point de vue de la survie globale, du contrôle de la maladie et de la toxicité, l'intérêt d'un traitement combinant une résection chirurgicale, une radiothérapie intra-opératoire et une radiothérapie externe

Aggressive local treatment containing intraoperative radiation therapy (IORT) for patients with isolated local recurrences of pancreatic cancer: a retrospective analysis

Roeder, Falk ; Timke, Carmen ; Uhl, Matthias ; Habl, Gregor ; Hensley, Frank ; Buechler, Markus ; Krempien, Robert ; Huber, Peter ; Debus, Juergen ; Werner, Jens

Purpose To evaluate the use of intraoperative radiation therapy (IORT) in the multimodality treatment of patients with isolated local recurrences of pancreatic cancer. Patients and Methods We retrospectively analyzed 36 patients with isolated local recurrences of pancreatic cancer who have been treated with a combination of surgery, IORT and EBRT. Median time from initial treatment to recurrence was 20 months. All patients were surgically explored. In 18 patients a gross total resection was [...]

Menée sur 328 patients atteints d'un cancer de la prostate traité sans succès par radiothérapie ou cryochirurgie entre 1994 et 2011 (âge : 45 à 81 ans), cette étude évalue, du point de vue des événements indésirables et de la survie, l'efficacité d'une cryochirurgie de sauvetage

Salvage Cryosurgery of the Prostate for Failure After Primary Radiotherapy or Cryosurgery: Long-term Clinical, Functional, and Oncologic Outcomes in a Large Cohort at a Tertiary Referral Centre

Sven, Wenske ; Scott, Quarrier ; Aaron, E. Katz

Background : Salvage cryosurgery (SC) is a recognised option for patients who fail either primary radiation or cryosurgery. Objective : To report outcomes of patients undergoing SC. Design, setting, and participants : A consecutive series of 396 patients who had failed either primary radiotherapy or cryosurgery underwent SC between October 1994 and August 2011. Outcome measurements and statistical analysis : Demographic and clinical parameters before primary and salvage treatment were [...]

A partir d'une revue systématique de la littérature publiée entre 1995 et 2010 (41 études, 5 597 patients), cette étude identifie les facteurs clinico-pathologiques et thérapeutiques associés à la survie sans récidive chez les patients atteints d'un cancer de la prostate traité par prostatectomie radicale et détermine les conditions permettant d'initier une radiothérapie de sauvetage

The Timing of Salvage Radiotherapy After Radical Prostatectomy : A Systematic Review

King, Christopher R.

Salvage radiotherapy (SRT) after radical prostatectomy can potentially eradicate residual microscopic disease. Defining the optimal patient and treatment factors is essential and is particularly relevant within the context of adjuvant vs early vs delayed postoperative radiotherapy (RT). A systematic review of all published SRT studies was performed to identify the pathologic, clinical, and treatment factors associated with relapse-free survival (RFS) after SRT. A total of 41 studies [...]

Mené sur 120 patients atteints d'un cancer localisé de la prostate, cet essai randomisé contrôlé compare, du point de vue des événements indésirables, des résultats fonctionnels et des niveaux sanguins postopératoires du PSA , l'efficacité de deux techniques de prostatectomie radicale, l'une assistée par robot et l'autre réalisée par laparoscopie

Randomised Controlled Trial Comparing Laparoscopic and Robot-assisted Radical Prostatectomy

Francesco, Porpiglia ; Ivano, Morra ; Marco Lucci, Chiarissi ; Matteo, Manfredi ; Fabrizio, Mele ; Susanna, Grande ; Francesca, Ragni ; Massimiliano, Poggio ; Cristian, Fiori

Background : The advantages of robot-assisted radical prostatectomy (RARP) over laparoscopic radical prostatectomy (LRP) have rarely been investigated in randomised controlled trials. Objective : To compare RARP and LRP in terms of the functional, perioperative, and oncologic outcomes. The main end point of the study was changes in continence 3 mo after surgery. Design, setting, and participants : From January 2010 to January 2011, 120 patients with organ-confined prostate cancer were enrolled [...]

Menée in vitro et in vivo, cette étude évalue un composé appelé AT13387, un inhibiteur de la protéine de choc thermique Hsp90, pour le traitement des tumeurs stromales gastro-intestinales sensibles ou résistantes à l'imatinib

The HSP90 Inhibitor, AT13387, Is Effective against Imatinib-Sensitive and -Resistant Gastrointestinal Stromal Tumor Models

Smyth, Tomoko ; Van Looy, Thomas ; Curry, Jayne E. ; Rodriguez-Lopez, Ana M. ; Wozniak, Agnieszka ; Zhu, Meijun ; Donsky, Rachel ; Morgan, Jennifer G. ; Mayeda, Mark ; Fletcher, Jonathan A. ; Schöffski, Patrick ; Lyons, John ; Thompson, Neil T. ; Wallis, Nicola G.

The majority of gastrointestinal stromal tumors (GIST) are characterized by activating mutations of KIT, an HSP90 client protein. Further secondary resistance mutations within KIT limit clinical responses to tyrosine kinase inhibitors, such as imatinib. The dependence of KIT and its mutated forms on HSP90 suggests that HSP90 inhibition might be a valuable treatment option for GIST, which would be equally effective on imatinib-sensitive and -resistant clones. We investigated the activity of [...]

Menée à l'aide de modèles murins, cette étude met en évidence l'activité antitumorale de glycosides cardiotoniques, notamment la digoxine, en association avec une chimiothérapie

Cardiac Glycosides Exert Anticancer Effects by Inducing Immunogenic Cell Death

Menger, Laurie ; Vacchelli, Erika ; Adjemian, Sandy ; Martins, Isabelle ; Ma, Yuting ; Shen, Shensi ; Yamazaki, Takahiro ; Sukkurwala, Abdul Qader ; Michaud, Mickaël ; Mignot, Grégoire ; Schlemmer, Frederic ; Sulpice, Eric ; Locher, Clara ; Gidrol, Xavier ; Ghiringhelli, François ; Modjtahedi, Nazanine ; Galluzzi, Lorenzo ; Andre, Fabrice ; Zitvogel, Laurence ; Kepp, Oliver ; Kroemer, Guido

Some successful chemotherapeutics, notably anthracyclines and oxaliplatin, induce a type of cell stress and death that is immunogenic, hence converting the patient’s dying cancer cells into a vaccine that stimulates antitumor immune responses. By means of a fluorescence microscopy platform that allows for the automated detection of the biochemical hallmarks of such a peculiar cell death modality, we identified cardiac glycosides (CGs) as exceptionally efficient inducers of immunogenic cell [...]

Menée in vivo, cette étude évalue les capacités de peptides artificiels à pénétrer spécifiquement à l'intérieur des cellules tumorales

Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems

Kondo, Eisaku ; Saito, Ken ; Tashiro, Yuichi ; Kamide, Kaeko ; Uno, Shusei ; Furuya, Tomoko ; Mashita, Masao ; Nakajima, Kiichiro ; Tsumuraya, Tomoyuki ; Kobayashi, Naoya ; Nishibori, Masahiro ; Tanimoto, Mitsune ; Matsushita, Masayuki

Cell-penetrating peptides have gained attention owing to their promise in noninvasive delivery systems. Among the identified cell-penetrating peptides, the TAT peptide has been preferentially used for transduction into cells of diverse origins. However, this activity is nonselective between neoplastic and non-neoplastic cells. Here we describe artificial cell-penetrating peptides that are selectively and efficiently incorporated into human tumour cells, according to their lineage. Ten [...]

Mené sur 18 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue l'aflibercept en combinaison avec du pemetrexed et du cisplatine

A phase I dose-escalation study of aflibercept administered in combination with pemetrexed and cisplatin in patients with advanced solid tumours

Diaz-Padilla, I. ; Siu, L. L. ; San Pedro-Salcedo, M. ; Razak, A. R. A. ; Colevas, A. D. ; Shepherd, F. A. ; Leighl, N. B. ; Neal, J. W. ; Thibault, A. ; Liu, L. ; Lisano, J. ; Gao, B. ; Lawson, E. B. ; Wakelee, H. A.

Background: To evaluate the safety, pharmacokinetics (PKs), and pharmacodynamics of aflibercept, and to identify the recommended phase II dose (RP2D) of aflibercept in combination with pemetrexed and cisplatin. Methods: Aflibercept was administered at escalating doses of 2, 4, or 6 mg kg−1 in combination with fixed doses of pemetrexed (500 mg m−2) plus cisplatin (75 mg m−2) every 3 weeks. Blood samples were collected for PK analyses. Serum antiaflibercept antibodies were quantified to assess [...]

Cet article passe en revue les perspectives offertes par le ciblage des protéines de la famille LOX, impliquées dans le remodelage du microenvironnement tumoral, pour le traitement des cancers

The rationale for targeting the LOX family in cancer

Barker, Holly E. ; Cox, Thomas R. ; Erler, Janine T.

The therapeutic targeting of extracellular proteins is becoming hugely attractive in light of evidence implicating the tumour microenvironment as pivotal in all aspects of tumour initiation and progression. Members of the lysyl oxidase (LOX) family of proteins are secreted by tumours and are the subject of much effort to understand their roles in cancer. In this Review we discuss the roles of members of this family in the remodelling of the tumour microenvironment and their paradoxical roles in [...]

Menée in vitro, cette étude évalue les perspectives offertes par des complexes protéiques appelés Atrimer pour induire une apoptose des cellules cancéreuses

Targeting TRAIL death receptor 4 with trivalent DR4 Atrimer™ complexes

Allen, Joshua E. ; Ferrini, Roger ; Dicker, David T. ; Batzer, Glenda ; Chen, Elise ; Oltean, Daniela I ; Lin, Bing ; Renshaw, Mark W ; Kretz-Rommel, Anke ; El-Deiry, Wafik S.

TNF-related apoptosis-inducing ligand (TRAIL) is a trimeric protein that potently induces apoptosis in cancer cells by binding to the trimeric death receptors (DR4 or DR5). Death receptors are attractive therapeutic targets through both the recombinant TRAIL ligand as well as receptor agonist monoclonal antibodies. While efficacy of the ligand is hampered by its short half-life, agonistic antibodies have a much longer half-life and have demonstrated some clinical efficacy as antitumor agents. [...]

Menée in vitro, in vivo et sur des échantillons sanguins prélevés sur des patients atteints d'une leucémie myéloïde aiguë, cette étude met en évidence l'intérêt du ciblage de la voie de signalisation CDK1 pour le traitement d'une leucémie présentant une mutation du gène FLT3

Targeting CDK1 promotes FLT3-activated acute myeloid leukemia differentiation through C/EBPα

Radomska, Hanna S. ; Alberich-Jordà, Meritxell ; Will, Britta ; Gonzalez, David ; Delwel, Ruud ; Tenen, Daniel G.

Mutations that activate the fms-like tyrosine kinase 3 (FLT3) receptor are among the most prevalent mutations in acute myeloid leukemias. The oncogenic role of FLT3 mutants has been attributed to the abnormal activation of several downstream signaling pathways, such as STAT3, STAT5, ERK1/2, and AKT. Here, we discovered that the cyclin-dependent kinase 1 (CDK1) pathway is also affected by internal tandem duplication mutations in FLT3. Moreover, we also identified C/EBPα, a [...]

Menée sur des lignées cellulaires, des modèles murins et des patients atteints d'une néoplasie myéloproliférative traitée à l'aide d'inhibiteurs de JAK2, cette étude met en évidence des mécanismes associés à la réponse thérapeutique

Heterodimeric JAK-STAT activation as a mechanism of persistence to JAK2 inhibitor therapy

Koppikar, Priya ; Bhagwat, Neha ; Kilpivaara, Outi ; Manshouri, Taghi ; Adli, Mazhar ; Hricik, Todd ; Liu, Fan ; Saunders, Lindsay M. ; Mullally, Ann ; Abdel-Wahab, Omar ; Leung, Laura ; Weinstein, Abby ; Marubayashi, Sachie ; Goel, Aviva ; Gonen, Mithat ; Estrov, Zeev ; Ebert, Benjamin L. ; Chiosis, Gabriela ; Nimer, Stephen D. ; Bernstein, Bradley E. ; Verstovsek, Srdan ; Levine, Ross L.

The identification of somatic activating mutations in JAK2 and in the thrombopoietin receptor gene (MPL) in most patients with myeloproliferative neoplasm (MPN) led to the clinical development of JAK2 kinase inhibitors. JAK2 inhibitor therapy improves MPN-associated splenomegaly and systemic symptoms but does not significantly decrease or eliminate the MPN clone in most patients with MPN. We therefore sought to characterize mechanisms by which MPN cells persist despite chronic inhibition of [...]

Menée sur des lignées celulaires et à l'aide de xénogreffes, cette étude évalue un composé appelé PBS-1086, un inhibiteur des voies canonique et non canonique de signalisation NF-kappaB, pour le traitement d'un myélome multiple en combinaison avec le bortezomib

Dual inhibition of canonical and non-canonical NF-κB pathways demonstrates significant anti-tumor activities in multiple myeloma

Fabre, Claire ; Mimura, Naoya ; Bobb, Kathryn ; Kong, Sun-Young ; Gorgun, Gullu ; Cirstea, Diana ; Hu, Yiguo ; Minami, Jiro ; Ohguchi, Hiroto ; Zhang, Jie ; Meshulam, Jeffrey ; Carrasco, Ruben ; Tai, Yu-Tzu ; Richardson, Paul G. ; Hideshima, Teru ; Anderson, Kenneth C.

Purpose: NF-

Menée in vitro et in vivo, cette étude évalue deux conjugués anticorps-médicaments ciblant la protéine de surface FcRL5, en combinaison avec le bortezomib ou le lénalidomide, pour le traitement d'un myélome multiple

FcRL5 as a Target of Antibody-Drug Conjugates for the Treatment of Multiple Myeloma

Elkins, Kristi ; Zheng, Bing ; Go, MaryAnn ; Slaga, Dionysos ; Du, Changchung ; Scales, Suzie J. ; Yu, Shang-Fan ; McBride, Jacqueline ; de Tute, Ruth ; Rawstron, Andy ; Jack, Andrew S ; Ebens, Allen ; Polson, Andrew G

Fc receptor-like 5 (FcRL5/FcRH5/IRTA2/CD307) is a surface protein expressed selectively on B-cells and plasma cells. We found that FcRL5 was expressed at elevated levels on the surface of plasma cells from the bone marrow of patients diagnosed with multiple myeloma (MM). This prevalence in MM and narrow pattern of normal expression suggest that FcRL5 could be a target for antibody-based therapies for MM, particularly antibody-drug conjugates (ADCs), potent cytotoxic drugs linked to antibodies [...]

Menée in vitro et in vivo, cette étude évalue l'activité antitumorale du ganetespib, un inhibiteur de la protéine de choc thermique Hsp90, pour le traitement de divers sous-types du cancer du poumon non à petites cellules, notamment les cancers présentant des mutations des gènes EGFR ou ERBB2

Ganetespib (STA-9090), a Non-Geldanamycin HSP90 Inhibitor, has Potent Antitumor Activity in In Vitro and In Vivo Models of Non-Small Cell Lung Cancer

Shimamura, Takeshi ; Perera, Samanthi A. ; Foley, Kevin P. ; Sang, Jim ; Rodig, Scott J. ; Inoue, Takayo ; Chen, Liang ; Li, Danan ; Carretero, Julian ; Li, Yu-Chen ; Sinha, Papiya ; Carey, Christopher D. ; Borgman, Christa L. ; Jimenez, John-Paul ; Meyerson, Matthew ; Ying, Weiwen ; Barsoum, James ; Wong, Kwok-Kin ; Shapiro, Geoffrey I.

Purpose: We describe the anticancer activity of ganetespib, a novel non-geldanamycin heat shock protein 90 (HSP90) inhibitor, in non-small cell lung cancer (NSCLC) models. Experimental Design: The activity of ganetespib was compared to that of the geldnamaycin 17-AAG in biochemical assays, cell lines and xenografts, and evaluated in an ERBB2 YVMA-driven mouse lung adenocarcinoma model. Results: Ganetespib blocked the ability of HSP90 to bind to biotinylated geldanamycin and disrupted the [...]

Menée à l'aide de xénogreffes, cette étude évalue l'activité antitumorale de nanoparticules d'or radioactives pour le traitement d'un cancer de la prostate

Laminin receptor specific therapeutic gold nanoparticles (198AuNP-EGCg) show efficacy in treating prostate cancer

Shukla, Ravi ; Chanda, Nripen ; Zambre, Ajit ; Upendran, Anandhi ; Katti, Kavita ; Kulkarni, Rajesh R. ; Nune, Satish Kumar ; Casteel, Stan W. ; Smith, Charles Jeffrey ; Vimal, Jatin ; Boote, Evan ; Robertson, J. David ; Kan, Para ; Engelbrecht, Hendrik ; Watkinson, Lisa D. ; Carmack, Terry L. ; Lever, John R. ; Cutler, Cathy S. ; Caldwell, Charles ; Kannan, Raghuraman ; Katti, Kattesh V.

Systemic delivery of therapeutic agents to solid tumors is hindered by vascular and interstitial barriers. We hypothesized that prostate tumor specific epigallocatechin-gallate (EGCg) functionalized radioactive gold nanoparticles, when delivered intratumorally (IT), would circumvent transport barriers, resulting in targeted delivery of therapeutic payloads. The results described herein support our hypothesis. We report the development of inherently therapeutic gold nanoparticles derived from [...]

Cet article passe en revue les travaux récents sur les inhibiteurs de mTOR pour le traitement d'un carcinome rénal non à cellules claires

Non-Clear Cell Renal Cell Carcinoma: Does the Mammalian Target of Rapamycin Represent a Rational Therapeutic Target?

Albiges, Laurence ; Molinié, Vincent ; Escudier, Bernard

Non-clear cell renal cell carcinomas (nccRCCs) comprise a heterogenous and poorly characterized group of tumor types for which few treatments have been approved. Although targeted therapies have become the cornerstones of systemic treatment for metastatic renal cell carcinoma, patients with nccRCC have been excluded from many pivotal clinical trials. As such, robust clinical evidence supporting the use of these agents in patients with nccRCC is lacking. Here, we review the disparate nccRCC [...]

Menée in vitro et à l'aide de xénogreffes de glioblastome, cette étude met en évidence un mécanisme de létalité synthétique entre des inhibiteurs de CDK et de PI3K

Dual blockade of lipid and cyclin-dependent kinases induces synthetic lethality in malignant glioma

Cheng, Christine K. ; Gustafson, W. Clay ; Charron, Elizabeth ; Houseman, Benjamin T. ; Zunder, Eli ; Goga, Andrei ; Gray, Nathanael S. ; Pollok, Brian ; Oakes, Scott A. ; James, C. David ; Shokat, Kevan M. ; Weiss, William A. ; Fan, Qi-Wen

Malignant glioma, the most common primary brain tumor, is generally incurable. Although phosphatidylinositol-3-kinase (PI3K) signaling features prominently in glioma, inhibitors generally block proliferation rather than induce apoptosis. Starting with an inhibitor of both lipid and protein kinases that induced prominent apoptosis and that failed early clinical development because of its broad target profile and overall toxicity, we identified protein kinase targets, the blockade of which showed [...]

Cet article passe en revue les perspectives offertes par l'usage de cellules souches comme systèmes de vectorisation de thérapies géniques pour le traitement des gliomes

Stem cell-based therapy for malignant glioma

Bexell, Daniel ; Svensson, Andreas ; Bengzon, Johan

Stem cells have been extensively investigated as tumour-tropic vectors for gene delivery to solid tumours. In this review, we discuss the potential for using stem cells as cellular vector systems in gene therapy for malignant gliomas, with a focus on neural stem cells, and multipotent mesenchymal stromal cells. Tumour cell-derived substances and factors associated with tumour-induced inflammation and tumour neovascularisation can specifically attract stem cells to invasive gliomas. Injected [...]

Cet article passe en revue les approches actuelles en matière de thérapies à base de lymphocytes T pour traiter une lymphoprolifération post-transplantation associée à une infection par le virus d'Epstein-Barr

T-cell therapy in the treatment of post-transplant lymphoproliferative disease

Bollard, Catherine M. ; Rooney, Cliona M. ; Heslop, Helen E.

Post-transplant lymphoproliferative diseases (PTLD) associated with Epstein-Barr virus (EBV) infection often develop after organ and haematopoietic stem-cell transplantation. These lymphoproliferative diseases are tumours that usually express all latent EBV viral proteins, and are therefore amenable to T-cell-based immune therapies, such as donor lymphocyte infusions and the adoptive transfer of EBV-specific cytotoxic T lymphocytes. In this Review, we describe current approaches of T-cell-based [...]

Mené sur 102 patients atteints d'un myélome multiple récidivant ou réfractaire, cet essai de phase II évalue, du point de vue de la survie sans progression, l'ajout de bevacizumab au bortezomib

Results from AMBER, a randomized phase 2 study of bevacizumab and bortezomib versus bortezomib in relapsed or refractory multiple myeloma

White, Darrell ; Kassim, Adetola ; Bhaskar, Birbal ; Yi, Jing ; Wamstad, Karen ; Paton, Virginia E.

BACKGROUND. Newer systemic therapies have significantly advanced the treatment of multiple myeloma, but additional agents are needed. Bortezomib is a proteasome inhibitor with efficacy in relapsed/refractory multiple myeloma that inhibits tumor angiogenesis, a process that has been implicated in multiple myeloma pathogenesis. METHODS. In AMBER(“A Randomized, Blinded, Placebo-Controlled, Multicenter, Phase II Study of Bevacizumab in Combination With Bortezomib in Patients With Relapsed or [...]

Cet article passe en revue les perspectives offertes par de nouvelles combinaisons à base de lénalidomide pour le traitement des myélomes multiples

Novel lenalidomide-based combinations for treatment of multiple myeloma

Cives, Mauro ; Simone, Valeria ; Brunetti, Oronzo ; Longo, Vito ; Silvestris, Franco

Lenalidomide (LEN) is an immunomodulatory drug (IMiD) which exerts tumoricidal effects and has immunomodulatory, anti-inflammatory and anti-angiogenic properties that synergistically keep the tumor in remission. It is currently approved as second-line therapy for multiple myeloma (MM) and for 5q defective myelodysplastic syndrome, while ongoing studies are at present evaluating its role in both solid and hematologic malignancies. Based on its high activity as an anti-myeloma drug with a good [...]

Cet article passe en revue les essais cliniques récents ayant évalué le fulvestrant pour le traitement d'un cancer du sein hormono-dépendant

Finding the right dose of fulvestrant in breast cancer

Estévez, L. ; Alvarez, I. ; Tusquets, I. ; Seguí, M. A. ; Muñoz, M. ; Fernández, Y. ; Lluch, A.

Fulvestrant is a selective estrogen receptor downregulator, behaving as a complete antagonist. It was initially approved, at a dose of 250mg, to treat hormone dependant breast cancer in second line setting. However, a series of pharmacological and pre-clinical studies have suggested that a higher dose of 500mg may be more effective. The present work summarizes and discusses clinical trials that have aimed to test the benefits of administering fulvestrant at a higher dose. The data support the [...]

Menée sur des lignées cellulaires de cancer de la prostate et à l'aide d'un modèle murin, cette étude montre que la molécule DHMEQ, un inhibiteur du NF-kappaB, peut augmenter la sensibilité des cellules tumorales aux rayonnements ionisants

Enhancement of radiosensitivity by a unique novel NF-kappaB inhibitor, DHMEQ, in prostate cancer

Kozakai, N. ; Kikuchi, E. ; Hasegawa, M. ; Suzuki, E. ; Ide, H. ; Miyajima, A. ; Horiguchi, Y. ; Nakashima, J. ; Umezawa, K. ; Shigematsu, N. ; Oya, M.

Background : Inducible activation of nuclear factor (NF)-

Menée sur 38 essais cliniques randomisés de traitements ayant bénéficié d'une autorisation de mise sur le marché par l'instance réglementaire américaine entre 2000 et 2010, cette méta-analyse évalue les toxicités associées

The Price We Pay for Progress: A Meta-Analysis of Harms of Newly Approved Anticancer Drugs

Niraula, Saroj ; Seruga, Bostjan ; Ocana, Alberto ; Shao, Tiffany ; Goldstein, Robyn ; Tannock, Ian F. ; Amir, Eitan

Purpose Registration of new anticancer drugs is usually based on results of randomized controlled trials (RCTs) showing improved efficacy when compared with standard therapy. There is relatively less emphasis on toxicity. In our study, we analyze serious toxicities of newly approved anticancer drugs reported in pivotal RCTs used for drug registration.Patients And methods We identified RCTs evaluating agents for the treatment of solid tumors approved by the US Food and Drug Administration [...]

Cet article présente une méthode de cryptographie utile pour envoyer les résultats de recherche à des individus ayant participé à une étude clinique tout en respectant leur vie privée

Reporting Actionable Research Results: Shared Secrets Can Save Lives

Hunter, Lawrence E. ; Hopfer, Christian ; Terry, Sharon F. ; Coors, Marilyn E.

In this Commentary, we describe a cryptographic method for returning research results to individuals who participate in clinical studies. Controlled use of this method, which relaxes the typical anonymization guarantee, can ensure that clinically actionable results reach participants while also addressing most privacy concerns.