Menée sur 54 patients atteints de la maladie de von Hippel-Lindau et d'un carcinome à cellules rénales (durée médiane de suivi : 67 mois), cette étude évalue les résultats clinico-pathologiques d'une chirurgie préservant les néphrons, du point de vue de la survie globale, de la survie spécifique et de la probabilité d'une seconde intervention chirurgicale

Nephron sparing surgery in von Hippel-Lindau associated renal cell carcinoma; clinicopathological long-term follow-up

Jilg, C. ; Neumann, Hartmut ; Gläsker, S. ; Schäfer, O. ; Leiber, C. ; Ardelt, P. ; Schwardt, M. ; Schultze-Seemann, W.

We evaluated the clinicopathological outcome of von Hippel-Lindau (VHL)-patients who had mainly undergone nephron sparing surgery (NSS) for renal cell carcinoma (RCC) when the tumour diameter has reached 4.0 cm. Multiple, bilateral RCC with high recurrence rates and subsequent repeated interventions, followed by increasing risk for end-stage renal failure and metastases is characteristic for VHL. NSS is widely used for VHL-associated RCC at 3.0 cm cut-off. 54 VHL patients underwent NSS, [...]

Menée sur 160 patients atteints d'un carcinome urothélial des voies urinaires supérieures et traités entre 1996 et 2011 (âge médian : 73 ans ; durée médiane de suivi : 38,2 mois), cette étude évalue, du point de vue de la survie globale, les résultats d'une résection par urétéroscopie en fonction du grade tumoral

Ureteroscopic and extirpative treatment of upper urinary tract urothelial carcinoma : a 15-year comprehensive review of 160 consecutive patients

Grasso, Michael ; Fishman, Andrew I. ; Cohen, Jacob ; Alexander, Bobby

Study Type – Therapy (case series)Level of Evidence 4What's known on the subject? and What does the study add?Upper urinary tract urothelial carcinomas (UTUC) have historically been treated with radical, extirpative surgery, primarily nephroureterectomy with bladder-cuff excision. In general, there has been growing interest in renal preservation, as evidenced by the broadening application of nephron-sparing surgery for renal parenchymal tumours. Beyond imperative reasons such as tumour in a [...]

Menée à partir de données portant sur 1 668 patients américains, cette étude de cohorte observationnelle compare la morbidité, la mortalité, la durée du séjour hospitalier et les coûts associés à deux techniques de cystectomie radicale, l'une par par voie ouverte et l'autre par laparoscopie assistée par robot

Comparative Analysis of Outcomes and Costs Following Open Radical Cystectomy Versus Robot-Assisted Laparoscopic Radical Cystectomy: Results From the US Nationwide Inpatient Sample

Hua-yin, Yu ; Nathanael, D. Hevelone ; Stuart, R. Lipsitz ; Keith, J. Kowalczyk ; Paul, L. Nguyen ; Toni, K. Choueiri ; Adam, S. Kibel ; Jim, C. Hu

Background : Although robot-assisted laparoscopic radical cystectomy (RARC) was first reported in 2003 and has gained popularity, comparisons with open radical cystectomy (ORC) are limited to reports from high-volume referral centers. Objective : To compare population-based perioperative outcomes and costs of ORC and RARC. Design, setting, and participants : A retrospective observational cohort study using the US Nationwide Inpatient Sample to characterize 2009 RARC compared with ORC use and [...]

Mené sur 107 patients atteints d'un cancer gastrique non résécable ou métastatique, cet essai de phase II évalue la toxicité et l'efficacité de l'ajout de sunitinib au docétaxel après l'échec d'une chimiothérapie à base de fluoropyrimidine et sels de platine

Randomised phase II trial of docetaxel and sunitinib in patients with metastatic gastric cancer who were previously treated with fluoropyrimidine and platinum

Yi, J. H. ; Lee, J. ; Park, S. H. ; Park, J. O. ; Yim, D. S. ; Park, Y. S. ; Lim, H. Y. ; Kang, W. K.

Background: Docetaxel is widely used as a chemotherapeutic agent for gastric cancer treatment. A combined regimen with sunitinib demonstrated a synergistic antitumour effect in a preclinical model. The aim of this study was to evaluate the efficacy and safety of this combination in patients with unresectable or metastatic advanced gastric cancer following failure of treatment with a fluoropyrimidine and platinum combination. Methods: This open-label, phase II, randomised trial enrolled patients [...]

Menée in vitro et in vivo, cette étude montre que CD47, qui est exprimé à la surface des cellules de tumeurs solides, a une fonction de blocage de la phagocytose, ce qui en fait une cible thérapeutique potentielle

The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

Willingham, Stephen B. ; Volkmer, Jens-Peter ; Gentles, Andrew J. ; Sahoo, Debashis ; Dalerba, Piero ; Mitra, Siddhartha S. ; Wang, Jian ; Contreras-Trujillo, Humberto ; Martin, Robin ; Cohen, Justin D. ; Lovelace, Patricia ; Scheeren, Ferenc A. ; Chao, Mark P. ; Weiskopf, Kipp ; Tang, Chad ; Volkmer, Anne Kathrin ; Naik, Tejaswitha J. ; Storm, Theresa A. ; Mosley, Adriane R. ; Edris, Badreddin ; Schmid, Seraina M. ; Sun, Chris K. ; Chua, Mei-Sze ; Murillo, Oihana ; Rajendran, Pradeep ; Cha, Adriel C. ; Chin, Robert K. ; Kim, Dongkyoon ; Adorno, Maddalena ; Raveh, Tal ; Tseng, Diane ; Jaiswal, Siddhartha ; Enger, Per Øyvind ; Steinberg, Gary K. ; Li, Gordon ; So, Samuel K. ; Majeti, Ravindra ; Harsh, Griffith R. ; van de Rijn, Matt ; Teng, Nelson N. H. ; Sunwoo, John B. ; Alizadeh, Ash A. ; Clarke, Michael F. ; Weissman, Irving L.

CD47, a “don't eat me” signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal [...]

Cet article passe en revue les perspectives offertes par la technologie d'induction de cellules souches pluripotentes pour le traitement des cancers

Pluripotent Stem Cell–Based Cancer Therapy: Promise and Challenges

Sharkis, Saul J. ; Jones, Richard J. ; Civin, Curt ; Jang, Yoon-Young

The development of induced pluripotent stem cell (iPSC) technology has generated enthusiasm about the therapeutic potential of these cells for treating a variety of diseases. However, the evidence that they actually will be clinically useful is limited. Here, we discuss the potential therapeutic applications of iPSCs for treating cancer and other diseases and highlight the current barriers restricting their use.

Cet article passe en revue les perspectives offertes par les récents développements d'immunothérapies, notamment dans le mélanome et le cancer du rein, pour les divers cancers épithéliaux

Raising the Bar: The Curative Potential of Human Cancer Immunotherapy

Rosenberg, Steven A.

Immunotherapy with interleukin-2 can cure 5 to 10% of patients with metastatic melanoma and renal cancer. Recent adoptive cell transfer (ACT) immunotherapies have improved cure rates in metastatic melanoma to 20 to 40%. Genetic engineering of T cells to express conventional alpha/beta T cell receptors or antibody-based chimeric antigen receptors provides an opportunity to extend ACT to patients with common epithelial cancers.

Menés sur 25 patients atteints d'un mélanome et 22 patientes atteintes d'un cancer ovarien épithélial, ces deux essais de phase II évaluent l'efficacité de vaccins recombinants ciblés sur l'antigène tumoral NY-ESO-1

Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients

Odunsi, Kunle ; Matsuzaki, Junko ; Karbach, Julia ; Neumann, Antje ; Mhawech-Fauceglia, Paulette ; Miller, Austin ; Beck, Amy ; Morrison, Carl D. ; Ritter, Gerd ; Godoy, Heidi ; Lele, Shashikant ; duPont, Nefertiti ; Edwards, Robert ; Shrikant, Protul ; Old, Lloyd J. ; Gnjatic, Sacha ; Jäger, Elke

Recombinant poxviruses (vaccinia and fowlpox) expressing tumor-associated antigens are currently being evaluated in clinical trials as cancer vaccines to induce tumor-specific immune responses that will improve clinical outcome. To test whether a diversified prime and boost regimen targeting NY-ESO-1 will result in clinical benefit, we conducted two parallel phase II clinical trials of recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1), followed by booster vaccinations with recombinant [...]

Mené sur 99 patients atteints de cancer, cet essai de phase I évalue le PF-00562271, le premier composé de la classe des inhibiteurs de la kinase d'adhérence focale

Safety, Pharmacokinetic, and Pharmacodynamic Phase I Dose-Escalation Trial of PF-00562271, an Inhibitor of Focal Adhesion Kinase, in Advanced Solid Tumors

Infante, Jeffrey R. ; Camidge, D. Ross ; Mileshkin, Linda R. ; Chen, Eric X. ; Hicks, Rodney J. ; Rischin, Danny ; Fingert, Howard ; Pierce, Kristen J. ; Xu, Huiping ; Roberts, W. Gregory ; Shreeve, S. Martin ; Burris, Howard A. ; Siu, Lillian L.

Purpose PF-00562271 is a novel inhibitor of focal adhesion kinase (FAK). The objectives of this study were to identify the recommended phase II dose (RP2D) and assess safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of PF-00562271.Patients and Methods Part 1 was a dose escalation without and with food. Part 2 enrolled specific tumor types in an expansion at the RP2D and also assessed the effect of PF-00562271 on single-dose midazolam PK in a subgroup [...]

Menée in vitro, cette étude met en évidence un mécanisme explicatif du rôle de suppresseur de tumeurs que pourrait jouer l'oridonine, un composé extrait de la plante Rabdosia rubescens, dans les leucémies myéloïdes aiguës

Targeting of AML1-ETO in t(8;21) Leukemia by Oridonin Generates a Tumor Suppressor–Like Protein

Zhen, Tao ; Wu, Chuan-Feng ; Liu, Ping ; Wu, Hai-Yan ; Zhou, Guang-Biao ; Lu, Ying ; Liu, Jian-Xiang ; Liang, Yang ; Li, Keqin Kathy ; Wang, Yue-Ying ; Xie, Yin-Yin ; He, Miao-Miao ; Cao, Huang-Ming ; Zhang, Wei-Na ; Chen, Li-Min ; Petrie, Kevin ; Chen, Sai-Juan ; Chen, Zhu

Nearly 60% of acute myeloid leukemia (AML) patients with the t(8;21)(q22;q22) translocation fail to achieve long-term disease-free survival. Our previous studies demonstrated that oridonin selectively induces apoptosis of t(8;21) leukemia cells and causes cleavage of AML1-ETO oncoprotein resulting from t(8;21), but the underlying mechanisms remain unclear. We show that oridonin interacted with glutathione and thioredoxin/thioredoxin reductase to increase intracellular reactive oxygen species, [...]

Mené sur 102 patients atteints d'un lymphome hodgkinien réfractaire ou récidivant ayant reçu une greffe autologue de cellules souches, cet essai de phase II évalue la toxicité et l'efficacité un conjugué anticorps-médicament, le brentuximab vedotin

Results of a Pivotal Phase II Study of Brentuximab Vedotin for Patients With Relapsed or Refractory Hodgkin's Lymphoma

Younes, Anas ; Gopal, Ajay K. ; Smith, Scott E. ; Ansell, Stephen M. ; Rosenblatt, Joseph D. ; Savage, Kerry J. ; Ramchandren, Radhakrishnan ; Bartlett, Nancy L. ; Cheson, Bruce D. ; de Vos, Sven ; Forero-Torres, Andres ; Moskowitz, Craig H. ; Connors, Joseph M. ; Engert, Andreas ; Larsen, Emily K. ; Kennedy, Dana A. ; Sievers, Eric L. ; Chen, Robert

Purpose Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. In phase I studies, brentuximab vedotin demonstrated significant activity with a favorable safety profile in patients with relapsed or refractory CD30-positive lymphomas.Patients and Methods In this multinational, open-label, phase II study, the efficacy and safety of brentuximab vedotin were evaluated in patients with relapsed [...]

Menée sur 31 patients atteints d'un mélanome porteur de mutations V600E/KBRAF, cette étude montre que la présence d'une mutation concomitante de l'exon 3 du gène MEK1 n'est pas nécessairement associée à une résistance thérapeutique à un inhibiteur de BRAF

Preexisting MEK1 Exon 3 Mutations in V600E/KBRAF Melanomas Do Not Confer Resistance to BRAF Inhibitors

Shi, Hubing ; Moriceau, Gatien ; Kong, Xiangju ; Koya, Richard C. ; Nazarian, Ramin ; Pupo, Gulietta M. ; Bacchiocchi, Antonella ; Dahlman, Kimberly B. ; Chmielowski, Bartosz ; Sosman, Jeffrey A. ; Halaban, Ruth ; Kefford, Richard F. ; Long, Georgina V. ; Ribas, Antoni ; Lo, Roger S.

BRAF inhibitors (BRAFi) induce antitumor responses in nearly 60% of patients with advanced V600E/KBRAF melanomas. Somatic activating MEK1 mutations are thought to be rare in melanomas, but their potential concurrence with V600E/KBRAF may be selected for by BRAFi. We sequenced MEK1/2 exon 3 in melanomas at baseline and upon disease progression. Of 31 baseline V600E/KBRAF melanomas, 5 (16%) carried concurrent somatic BRAF/MEK1 activating mutations. Three of 5 patients with BRAF/MEK1 double-mutant [...]

Menée in vitro et in vivo, cette étude évalue l'intérêt d'un anticorps bloquant l'action d'une glycoprotéine biliaire, CEACAM1, pour l'immunothérapie du mélanome

Novel immunotherapy for malignant melanoma with a monoclonal antibody that blocks CEACAM1 homophilic interactions

Ortenberg, Rona ; Sapir, Yair ; Raz, Lee ; Hershkovitz, Liat ; Ben Arav, Ayelet ; Sapoznik-Danon, Sivan ; Barshack, Iris ; Avivi, Camila ; Berkun, Yackov ; Besser, Michal J ; Ben-Moshe, Tehila ; Schachter, Jacob ; Markel, Gal

CEACAM1 (Biliary glycoprotein-1, CD66a) was reported as a strong clinical predictor of poor prognosis in melanoma. We have previously identified CEACAM1 as a tumor escape mechanism from cytotoxic lymphocytes. Here we present substantial evidence in-vitro and in-vivo that blocking of CEACAM1 function with a novel mAb (MRG1) is a promising strategy for cancer immunotherapy. MRG1, a murine IgG1 mAb, was raised against human CEACAM1. It recognizes the CEACAM1-specific N-domain with high affinity [...]

Mené sur 29 patients atteints d'un myélome multiple récidivant ou réfractaire (âge médian : 63 ans), cet essai multicentrique de phase I/II évalue un traitement combinant bendamustine, lénalidomide et dexaméthasone (durée médiane de suivi : 13 mois)

Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase I/II open-label, dose escalation study

Lentzsch, Suzanne ; O'Sullivan, Amy ; Kennedy, Ryan C. ; Abbas, Mohammad ; Dai, Lijun ; Pregja, Silvana Lalo ; Burt, Steve ; Boyiadzis, Michael ; Roodman, G. David ; Mapara, Markus Y. ; Agha, Mounzer ; Waas, John ; Shuai, Yongli ; Normolle, Daniel ; Zonder, Jeffrey A.

This multicenter phase I/II trial investigated the combination of bendamustine (BEN), lenalidomide (LEN) and dexamethasone (DEX) (BLD) in repeating 4-week cycles as treatment for relapsed multiple myeloma (MM). Patients ≥18 years with symptomatic relapsed or refractory MM were enrolled. Phase I established maximum tolerated dose (MTD). Phase II assessed overall response rate (ORR) at the MTD. Secondary endpoints included progression free survival (PFS) and overall survival (OS). 29 evaluable [...]

Menée in vitro et in vivo, cette étude évalue l'activité antitumorale d'un anticorps anti-EpCAM, conjugué avec l'alpha-amatinine, sur des carcinomes pancréatiques

Therapeutic Potential of Amanitin-Conjugated Anti-Epithelial Cell Adhesion Molecule Monoclonal Antibody Against Pancreatic Carcinoma

Moldenhauer, Gerhard ; Salnikov, Alexei V. ; Lüttgau, Sandra ; Herr, Ingrid ; Anderl, Jan ; Faulstich, Heinz

Background Human epithelial cell adhesion molecule (EpCAM) is overexpressed in many cancers. Anti-EpCAM antibodies have shown promise in preclinical studies, but showed no tumor regression in a recent phase II clinical trial. Therefore, we generated a novel anti-EpCAM antibody–drug conjugate and assessed whether it showed enhanced antitumor effects.Methods Chemical cross-linking was conducted to covalently conjugate α-amanitin, a toxin known to inhibit DNA transcription, with chiHEA125, a [...]

Menée sur un modèle murin de léiomyosarcome, cette étude évalue l'efficacité d'un nouvel anticorps anti CD47 sur la croissance des tumeurs primitives et le développement de métastases

Antibody therapy targeting the CD47 protein is effective in a model of aggressive metastatic leiomyosarcoma

Edris, Badreddin ; Weiskopf, Kipp ; Volkmer, Anne K. ; Volkmer, Jens-Peter ; Willingham, Stephen B. ; Contreras-Trujillo, Humberto ; Liu, Jie ; Majeti, Ravindra ; West, Robert B. ; Fletcher, Jonathan A. ; Beck, Andrew H. ; Weissman, Irving L. ; van de Rijn, Matt

Antibodies against CD47, which block tumor cell CD47 interactions with macrophage signal regulatory protein-α, have been shown to decrease tumor size in hematological and epithelial tumor models by interfering with the protection from phagocytosis by macrophages that intact CD47 bestows upon tumor cells. Leiomyosarcoma (LMS) is a tumor of smooth muscle that can express varying levels of colony-stimulating factor-1 (CSF1), the expression of which correlates with the numbers of tumor-associated [...]

Menée sur des lignées cellulaires de sarcome d'Ewing, cette étude met en évidence des mécanismes associés à l'activité antitumorale d'un composé appelé RITA (Reactivation of p53 and Induction of Tumor cell Apoptosis)

IGF-1R/MDM2 relationship confers enhanced sensitivity to RITA in Ewing's sarcoma cells

Di Conza, Giusy ; Buttarelli, Marianna ; Monti, Olimpia ; Pellegrino, Marsha ; Mancini, Francesca ; Pontecorvi, Alfredo ; Scotlandi, Katia ; Moretti, Fabiola

Ewing's sarcoma is one of the most frequent bone cancers in adolescence. Although multi-disciplinary therapy has improved the survival rate for localized tumors, a critical step is the development of new drugs to improve the long term outcome of recurrent and metastatic disease and to reduce side-effects of conventional therapy. Here, we demonstrate that the small molecule RITA (Reactivation of p53 and Induction of Tumor cell Apoptosis, NSC652287) is highly effective in reducing growth and [...]

Cet article passe en revue les travaux récents sur la diversité moléculaire des cancers du sein triplement négatifs et analyse les perspectives offertes par l'iniparib, en combinaison avec une chimiothérapie, pour le traitement de cette maladie à pronostic défavorable

Dissecting the Heterogeneity of Triple-Negative Breast Cancer

Metzger-Filho, Otto ; Tutt, Andrew ; de Azambuja, Evandro ; Saini, Kamal S. ; Viale, Giuseppe ; Loi, Sherene ; Bradbury, Ian ; Bliss, Judith M. ; Azim, Hatem A. ; Ellis, Paul ; Di Leo, Angelo ; Baselga, Jose ; Sotiriou, Christos ; Piccart-Gebhart, Martine

Triple-negative breast cancer (TNBC) accounts for 15% to 20% of breast cancers. It is a heterogeneous disease, not only on the molecular level, but also on the pathologic and clinical levels. TNBC is associated with a significantly higher probability of relapse and poorer overall survival in the first few years after diagnosis when compared with other breast cancer subtypes. This is observed despite its usual high sensitivity to chemotherapy. In the advanced setting, responses observed with [...]

Mené sur 88 patientes atteintes d'un cancer du sein HER2+ localement récidivant ou métastatique, cet essai de phase II évalue la toxicité et l'efficacité d'un traitement combinant bevacizumab, trastuzumab et capécitabine (durée médiane de suivi : 8,8 mois)

Phase II Study of Bevacizumab in Combination with Trastuzumab and Capecitabine as First-Line Treatment for HER-2-positive Locally Recurrent or Metastatic Breast Cancer

Martin, Miguel ; Makhson, Anatoly ; Gligorov, Joseph ; Lichinitser, Mikhail ; Lluch, Ana ; Semiglazov, Vladimir ; Scotto, Nana ; Mitchell, Lada ; Tjulandin, Sergei

Abstract We report the first results from a phase II, open-label study designed to evaluate the efficacy and safety of bevacizumab in combination with trastuzumab and capecitabine as first-line therapy for human epidermal growth factor receptor (HER)-2-positive locally recurrent (LR) or metastatic breast cancer (MBC). Patients were aged ≥18 years with confirmed breast adenocarcinoma, measurable LR/MBC and documented HER-2-positive disease. Patients received bevacizumab (15 mg/kg on day 1) plus [...]

Menée à l'aide de xénogreffes de tumeurs prélevées sur des patientes atteintes d'un cancer du sein triple négatif, cette étude évalue l'efficacité de l'irinotecan et d'un inhibiteur de Chk1, en monothérapie ou en combinaison

Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models

Ma, Cynthia X. ; Cai, Shirong ; Li, Shunqiang ; Ryan, Christine E. ; Guo, Zhanfang ; Schaiff, W. Timothy ; Lin, Li ; Hoog, Jeremy ; Goiffon, Reece J. ; Prat, Aleix ; Aft, Rebecca L. ; Ellis, Matthew J. ; Piwnica-Worms, Helen

Patients with triple-negative breast cancer (TNBC) — defined by lack of estrogen receptor and progesterone receptor expression as well as lack of human epidermal growth factor receptor 2 (HER2) amplification — have a poor prognosis. There is a need for targeted therapies to treat this condition. TNBCs frequently harbor mutations in TP53, resulting in loss of the G1 checkpoint and reliance on checkpoint kinase 1 (Chk1) to arrest cells in response to DNA damage. Previous studies have shown that [...]

Cet article passe en revue les travaux récents sur de nouveaux traitements des cancers du sein et de l'estomac surexprimant HER2

Improving Treatment of HER2-Positive Cancers: Opportunities and Challenges

Stern, Howard M.

Amplification of the ERBB2 gene, which encodes human epidermal growth factor receptor 2 (HER2), causes the overexpression of a major proliferative driver for a subset of breast and gastric cancers. Treatments for patients with HER2-positive cancer include the monoclonal antibody trastuzumab and, in the case of metastatic breast cancer, the tyrosine kinase inhibitor lapatinib. Despite significant improvement in patient outcome as a result of these therapies, challenges remain. This Review [...]

Menée in vitro et in vivo, cette étude évalue l'intérêt d'une molécule dotée de propriétés anti-invasives, Imipramine Blue, en combinaison avec la doxorubicine sous forme liposomale pour le traitement des gliomes

Anti-Invasive Adjuvant Therapy with Imipramine Blue Enhances Chemotherapeutic Efficacy Against Glioma

Munson, Jennifer M. ; Fried, Levi ; Rowson, Sydney A. ; Bonner, Michael Y. ; Karumbaiah, Lohitash ; Diaz, Begoña ; Courtneidge, Sara A. ; Knaus, Ulla G. ; Brat, Daniel J. ; Arbiser, Jack L. ; Bellamkonda, Ravi V.

The invasive nature of glioblastoma (GBM) represents a major clinical challenge contributing to poor outcomes. Invasion of GBM into healthy tissue restricts chemotherapeutic access and complicates surgical resection. Here, we test the hypothesis that an effective anti-invasive agent can “contain” GBM and increase the efficacy of chemotherapy. We report a new anti-invasive small molecule, Imipramine Blue (IB), which inhibits invasion of glioma in vitro when tested against several models. IB [...]

Mené sur 265 patientes atteintes d'un cancer séreux de l'ovaire de haut grade, récidivant et sensible au platine, cet essai de phase II évalue, du point de vue de la survie sans progression, l'olaparib, un inhibiteur de PARP

Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer

Ledermann, Jonathan ; Harter, Philipp ; Gourley, Charlie ; Friedlander, Michael ; Vergote, Ignace ; Rustin, Gordon ; Scott, Clare ; Meier, Werner ; Shapira-Frommer, Ronnie ; Safra, Tamar ; Matei, Daniela ; Macpherson, Euan ; Watkins, Claire ; Carmichael, James ; Matulonis, Ursula

Background: Olaparib (AZD2281) is an oral poly(adenosine diphosphate [ADP]–ribose) polymerase inhibitor that has shown antitumor activity in patients with high-grade serous ovarian cancer with or without BRCA1 or BRCA2 germline mutations. Methods: We conducted a randomized, double-blind, placebo-controlled, phase 2 study to evaluate maintenance treatment with olaparib in patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer who had received two or more platinum-based [...]

Mené sur 1 050 patients atteints d'un cancer de la prostate métastatique et résistant à la castration, cet essai de phase III évalue, du point de vue de la survie globale, l'ajout de bevacizumab à un traitement combinant docétaxel et prednisone

Randomized, Double-Blind, Placebo-Controlled Phase III Trial Comparing Docetaxel and Prednisone With or Without Bevacizumab in Men With Metastatic Castration-Resistant Prostate Cancer: CALGB 90401

Kelly, William Kevin ; Halabi, Susan ; Carducci, Michael ; George, Daniel ; Mahoney, John F. ; Stadler, Walter M. ; Morris, Michael ; Kantoff, Philip ; Monk, J. Paul ; Kaplan, Ellen ; Vogelzang, Nicholas J. ; Small, Eric J.

Purpose A randomized, placebo-controlled study based on preclinical and clinical data that supports the potential role of vascular endothelial growth factor in prostate cancer was performed to evaluate the addition of bevacizumab to standard docetaxel and prednisone therapy in patients with metastatic castration-resistant prostate cancer (mCRPC).Patients and Methods Patients with chemotherapy-naive progressive mCRPC with Eastern Cooperative Oncology Group performance status ≤ 2 and adequate [...]

Cet article fait le point sur les différentes modalités thérapeutiques personnalisées intégrant une radiothérapie pour traiter un lymphome de Hodgkin classique chez l'adulte

Tailored strategies for radiation therapy in classical Hodgkin's lymphoma

Terezakis, Stephanie A. ; Kasamon, Yvette L.

Radiotherapeutic advances have contributed to the evolution of Hodgkin's lymphoma (HL) treatment paradigms. A reduction in radiation therapy (RT) field size and dose has the potential to significantly impact the therapeutic ratio by diminishing late toxicities while maintaining curability. Substantial progress in risk stratification has contributed to the development of tailored RT strategies which address both field design as well as dose. Technologic improvements have also enhanced the [...]

Cet article analyse les raisons de la sous-estimation des effets indésirables (cardiotoxicité) associés au sunitinib dans les publications des premiers essais cliniques de cette molécule

Underestimating Cardiac Toxicity in Cancer Trials: Lessons Learned?

Witteles, Ronald M. ; Telli, Melinda

Sunitinib (Sutent; Pfizer, New York, NY) represents one of the most successful cancer therapies, with US Food and Drug Administration (FDA) approval for three malignancies and ongoing trials in more than 30 tumor types. It also represents an instructive example revealing how adverse events can be vastly underestimated. The purpose of this article is to critically evaluate the history of the underrecognition of the cardiac toxicity of sunitinib and to propose solutions to improve adverse event [...]

A partir de données portant sur 1 181 patients ayant été inclus dans un essai clinique de phase I au Centre MD Anderson, cette étude évalue l'intérêt d'un indicateur, le score du Royal Marsden Hospital, pour déterminer la survie des patients

Survival of 1,181 Patients in a Phase I Clinic: The MD Anderson Clinical Center for Targeted Therapy Experience

Wheler, Jennifer J. ; Tsimberidou, Apostolia M. ; Hong, David S. ; Naing, Aung ; Falchook, Gerald S. ; Sarina, Piha-Paul ; Fu, Siqing ; Moulder, Stacy L. ; Stephen, Bettzy ; Wen, Sijin ; Kurzrock, Razelle

ABSTRACT Background: In order to determine if the Royal Marsden Hospital (RMH) prognostic score for phase I patients can be validated in a large group of individuals seen in a different center, and if other prognostic variables are also relevant, we present an analysis of 1,181 patients treated in the MD Anderson Cancer Center (MDACC) Phase I clinic. Methods: Medical records of 1,181 consecutive patients who were treated on at least one trial in the Phase I clinic were reviewed. Results: The [...]

Cet article passe en revue les obstacles associés à la réforme du système des essais cliniques en oncologie

Oncology trials-the elephant in the room

Kirk, Rebecca ; Hutchinson, Lisa