Menée in vitro et à l'aide de xénogreffes sur des modèles murins, cette étude montre que RTA 408, un inhibiteur du facteur nucléaire NF-κB, peut protéger l'appareil digestif des dommages collatéraux causés par la radiothérapie et inhiber la croissance des cellules cancéreuses de la prostate

Radiation Protection of the Gastrointestinal Tract and Growth Inhibition of Prostate Cancer Xenografts by a Single Compound

Alexeev, Vitali ; Lash, Elizabeth ; Aguillard, April ; Corsini, Laura ; Bitterman, Avi ; Ward, Keith ; Dicker, Adam P. ; Linnenbach, Alban ; Rodeck, Ulrich

Normal tissue toxicity markedly reduces the therapeutic index of genotoxic anticancer agents, including ionizing radiation. Countermeasures against tissue damage caused by radiation are limited by their potential to also protect malignant cells and tissues. Here, we tested a panel of signal transduction modifiers for selective radioprotection of normal but not tumor tissues. These included three inhibitors of GSK3 (LiCl, SB216763, and SB415286) and two inhibitors of NF-κB (ethyl pyruvate and [...]

Menée in vitro et à l'aide d'un modèle murin orthotopique de gliome, cette étude montre qu'un traitement combinant cannabidiol et Delta-9-tétrahydrocannabinol peut améliorer l'efficacité d'une radiothérapie

The Combination of Cannabidiol and Delta9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model

Scott, Katherine A. ; Dalgleish, Angus G. ; Liu, Wai M.

High-grade glioma is one of the most aggressive cancers in adult humans and long-term survival rates are very low as standard treatments for glioma remain largely unsuccessful. Cannabinoids have been shown to specifically inhibit glioma growth as well as neutralize oncogenic processes such as angiogenesis. In an attempt to improve treatment outcome, we have investigated the effect of Delta

A partir d'une revue de la littérature, cet article analyse le rôle d'une surrénalectomie endoscopique et d'une surrénalectomie par voie ouverte dans le traitement de petites tumeurs malignes de la glande surrénale

What is the appropriate role of minimally invasive vs. open surgery for small adrenocortical cancers?

Bellantone, Rocco ; Lombardi, Celestino P. ; Raffaelli, Marco

Purpose of review : The role of endoscopic adrenalectomy for adrenocortical carcinoma is the most controversial and debated points in adrenal surgery. We reviewed the most recent literature on this topic. Recent findings : From the amount of available data (even if not conclusive), the following could be extrapolated: first, for patients with apparently localized disease the adrenal gland should be removed en bloc with the entire retroperitoneal fat pad, which also includes some periadrenal [...]

Menée à partir de données portant sur 64 patients atteints d'un carcinome du canal anal, cette étude compare l'efficacité, du point de vue du contrôle loco-régional et de la survie spécifique à 5 ans, et la toxicité d'une arc-thérapie volumétrique avec modulation d'intensité et d'une radiothérapie conformationnelle

Radiation therapy of anal canal cancer: from conformal therapy to volumetric modulated arc therapy

Tozzi, Angelo ; Cozzi, Luca ; Iftode, Cristina ; Ascolese, AnnaMaria ; Campisi, Maria ; Clerici, Elena ; Comito, Tiziana ; De Rose, Fiorenza ; Fogliata, Antonella ; Franzese, Ciro ; Mancosu, Pietro ; Navarria, Piera ; Tomatis, Stefano ; Villa, Elisa ; Scorsetti, Marta

Background : To appraise the role of volumetric modulated arc (RapidArc, RA) in the treatment of anal canal carcinoma (ACC). Methods : A retrospective analysis has been conducted on 36 patients treated with RA since 2009 comparing outcome against a group of 28 patients treated with conformal therapy (CRT). RA treatments were prescribed with SIB technique with 59.4Gy to the primary tumor and nodes and 49.5Gy to the elective nodes. CRT was sequentially delivered with 45Gy to the pelvic target and [...]

Menée à partir de données portant sur 1 285 patients atteints d'un cancer de la prostate traité entre 2006 et 2010, cette étude évalue la toxicité d'une protonthérapie sur le système digestif, identifie les facteurs associés aux saignements du rectum ainsi que les protocoles permettant de limiter l'exposition des tissus sains aux rayonnements ionisants

Rectal Toxicity After Proton Therapy For Prostate Cancer: An Analysis of Outcomes of Prospective Studies Conducted at the University of Florida Proton Therapy Institute

Colaco, Rovel J. ; Hoppe, Bradford S. ; Flampouri, Stella ; McKibben, Brian T. ; Henderson, Randal H. ; Bryant, Curtis ; Nichols, Romaine C. ; Mendenhall, William M. ; Li, Zuofeng ; Su, Zhong ; Morris, Christopher G. ; Mendenhall, Nancy P.

Purpose : Study goals were to characterize gastrointestinal effects of proton therapy (PT) in a large cohort of patients treated for prostate cancer, identify factors associated with rectal bleeding (RB), and compare RB between patients receiving investigational protocols versus those in outcome-tracking protocols. Methods and Materials : A total of 1285 consecutive patients were treated with PT between August 2006 and May 2010. Potential pre-existing clinical and treatment-related risk factors [...]

A partir d'une revue systématique de la littérature publiée entre 1966 et 2014 (120 articles), cette étude fait le point sur le diagnostic et la prise en charge thérapeutique d'un carcinome urothélial in situ

Diagnosis and Management of Urothelial Carcinoma In Situ of the Lower Urinary Tract: A Systematic Review

Casey, Rowan G. ; Catto, James W. F. ; Cheng, Liang ; Cookson, Michael S. ; Herr, Harry ; Shariat, Sharokh ; Witjes, J. Alfred ; Black, Peter C.

Context : Urothelial carcinoma in situ (CIS) has a high propensity for progression. It is usually reported within the heterogeneous context of non–muscle-invasive bladder cancer (NMIBC) but warrants special consideration. Objective : To review the contemporary literature on the diagnosis and management of CIS. Evidence acquisition : A systematic search using broad terms to capture the diagnosis and treatment of CIS was performed according to Preferred Reporting Items for Systematic Reviews and [...]

Cet article passe en revue les perspectives offertes par la combinaison de thérapies ciblées et d'immunothérapies pour le traitement des cancers

Universes Collide: Combining Immunotherapy with Targeted Therapy for Cancer

Wargo, Jennifer A. ; Cooper, Zachary A. ; Flaherty, Keith T.

There have been significant advances in the past several years with regard to targeted therapy and immunotherapy for cancer. This is highlighted in melanoma, where treatment with targeted therapy (against the BRAF oncoprotein) results in responses in the majority of patients, although the duration of response is limited. In contrast, treatment with immunotherapy results in a lower response rate, but one that tends to be more durable. Insights about mechanisms of response and potential synergy [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude met en évidence des mécanismes suggérant l'intérêt d'une stratégie thérapeutique basée sur l'inhibition de MCT1 et MCT4, seule ou en combinaison avec la phenformine, pour le traitement de tumeurs dont le métabolisme est fortement glycolytique

Genetic Disruption of Lactate/H+ Symporters (MCTs) and their Subunit CD147/BASIGIN Sensitizes Glycolytic Tumor Cells to Phenformin

Marchiq, Ibtissam ; Le Floch, Renaud ; Roux, Danièle ; Simon, Marie-Pierre ; Pouyssegur, Jacques

Rapidly growing glycolytic tumors require energy and intracellular pH (pHi) homeostasis through the activity of two major MonoCarboxylate Transporters, MCT1 and the hypoxia-inducible MCT4, in intimate association with the glycoprotein CD147/BASIGIN (BSG). To further explore and validate the blockade of lactic acid export as an anticancer strategy, we disrupted, via Zinc Finger Nucleases, MCT4 and BASIGIN genes in colon adenocarcinoma (LS174T) and glioblastoma (U87) human cell lines. First, we [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes suggérant l'intérêt du cabozantinib pour améliorer l'efficacité d'une immunothérapie

Dual effects of a targeted small-molecule inhibitor (cabozantinib) on immune-mediated killing of tumor cells and immune tumor microenvironment permissiveness when combined with a cancer vaccine

Kwilas, Anna ; Ardiani, Andressa ; Donahue, Renee ; Aftab, Dana ; Hodge, James

BACKGROUND:Growing awareness of the complexity of carcinogenesis has made multimodal therapies for cancer increasingly compelling and relevant. In recent years, immunotherapy has gained acceptance as an active therapeutic approach to cancer treatment, even though cancer is widely considered an immunosuppressive disease. Combining immunotherapy with targeted agents that have immunomodulatory capabilities could significantly improve its efficacy. METHODS:We evaluated the ability of cabozantinib, [...]

Menée in vitro et in vivo, cette étude met en évidence l'activité antitumorale d'un composé appelé AZD8186, un inhibiteur de la signalisation PI3Kbeta, seul ou en combinaison avec du docétaxel, dans des tumeurs du sein triplement négatives et des tumeurs de la prostate n'exprimant pas PTEN

Inhibition of PI3Kbeta signaling with AZD8186 inhibits growth of PTEN deficient breast and prostate tumour alone and in combination with docetaxel

Barry, Simon T. ; Hancox, Urs ; Cosulich, Sabina ; Hanson, Lyndsey ; Trigwell, Cath ; Lenaghan, Carol ; Ellston, Rebecca ; Dry, Hannah ; Crafter, Claire ; Barlaam, Bernard ; Fitzek, Martina ; Smith, Paul D. ; Ogilvie, Donald ; D'Cruz, Celina ; Castriotta, Lillian ; Wedge, Stephen R. ; Ward, Lara ; Powell, Steve ; Lawson, Mandy ; Davies, Barry R ; Harrington, Elizabeth A ; Foster, Emily ; Cumberbatch, Marie ; Green, Stephen

Loss of PTEN protein results in upregulation of the PI3K/AKT pathway, which appears dependent on the PI3Kβ isoform. Inhibitors of PI3Kβ have potential to reduce growth of tumours in which loss of PTEN drives tumour progression. We have developed a small molecule inhibitor of PI3Kβ and PI3Kδ (AZD8186) and assessed its anti-tumour activity across a panel of cell lines. We have then explored the anti-tumour effects as single agent and in combination with docetaxel in triple negative breast (TNBC) [...]

Menée à l'aide de xénogreffes dérivées de tumeurs primitives de l'ovaire, cette étude met en évidence une surexpression du récepteur ROR1 dans les cellules souches cancéreuses ovariennes et suggère l'intérêt d'une stratégie thérapeutique basée sur l'inhibition de ROR1

Ovarian cancer stem cells express ROR1, which can be targeted for anti–cancer-stem-cell therapy

Zhang, Suping ; Cui, Bing ; Lai, Hsien ; Liu, Grace ; Ghia, Emanuela M. ; Widhopf, George F. ; Zhang, Zhuhong ; Wu, Christina C. N. ; Chen, Liguang ; Wu, Rongrong ; Schwab, Richard ; Carson, Dennis A. ; Kipps, Thomas J.

Although initially responsive to chemotherapy, many patients with ovarian cancer subsequently develop relapsed and potentially fatal metastatic disease, which is thought to develop from cancer stem cells (CSCs) that are relatively resistant to conventional therapy. Here, we show that CSCs express a type I receptor tyrosine kinase-like orphan receptor (ROR1), which is expressed during embryogenesis and by many different cancers, but not normal postpartum tissues. Ovarian cancers with high levels [...]

Menée à l'aide d'un modèle murin de cancer du poumon induit par la mutation G12D du gène KRAS, cette étude met en évidence l'activité antitumorale d'un traitement combinant rapamycine et bisphosphonates lipophiliques

A combination therapy for KRAS-driven lung adenocarcinomas using lipophilic bisphosphonates and rapamycin

Xia, Yifeng ; Liu, Yi-Liang ; Xie, Yonghua ; Zhu, Wei ; Guerra, Francisco ; Shen, Shen ; Yeddula, Narayana ; Fischer, Wolfgang ; Low, William ; Zhou, Xiaoying ; Zhang, Yonghui ; Oldfield, Eric ; Verma, Inder M.

Lung cancer is the most common human malignancy and leads to about one-third of all cancer-related deaths. Lung adenocarcinomas harboring KRAS mutations, in contrast to those with EGFR and EML4-ALK mutations, have not been successfully targeted. We describe a combination therapy for treating these malignancies with two agents: a lipophilic bisphosphonate and rapamycin. This drug combination is much more effective than either agent acting alone in the KRAS G12D–induced mouse lung model. [...]

Menée à partir d'échantillons tumoraux prélevés sur 6 patientes atteintes d'un cancer métastatique du sein présentant une mutation activatrice de la signalisation PIK3CA, puis sur des lignées cellulaires et à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels l'apparition parallèle d'une perte d'expression du gène PTEN dans différents sites métastatiques favorise la résistance à un composé appelé BYL719, un inhibiteur de PI3Kalpha

Convergent loss of PTEN leads to clinical resistance to a PI(3)Kalpha inhibitor

Juric, Dejan ; Castel, Pau ; Griffith, Malachi ; Griffith, Obi L. ; Won, Helen H. ; Ellis, Haley ; Ebbesen, Saya H. ; Ainscough, Benjamin J. ; Ramu, Avinash ; Iyer, Gopa ; Shah, Ronak H. ; Huynh, Tiffany ; Mino-Kenudson, Mari ; Sgroi, Dennis ; Isakoff, Steven ; Thabet, Ashraf ; Elamine, Leila ; Solit, David B. ; Lowe, Scott W. ; Quadt, Cornelia ; Peters, Malte ; Derti, Adnan ; Schegel, Robert ; Huang, Alan ; Mardis, Elaine R. ; Berger, Michael F. ; Baselga, Jose ; Scaltriti, Maurizio

Broad and deep tumour genome sequencing has shed new light on tumour heterogeneity and provided important insights into the evolution of metastases arising from different clones. There is an additional layer of complexity, in that tumour evolution may be influenced by selective pressure provided by therapy, in a similar fashion to that occurring in infectious diseases. Here we studied tumour genomic evolution in a patient (index patient) with metastatic breast cancer bearing an activating [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes de cancer du sein, cette étude met en évidence des mécanismes suggèrant l'intérêt d'une stratégie thérapeutique ciblée sur la protéine TopBP1

Targeting TopBP1 at a convergent point of multiple oncogenic pathways for cancer therapy

Chowdhury, Pinki ; Lin, Gregory E. ; Liu, Kang ; Song, Yongcheng ; Lin, Fang-Tsyr ; Lin, Weei-Chin

The progression of many solid tumours is driven by deregulation of multiple common pathways, particularly Rb, PI(3)K/Akt and p53. Prior studies identified TopBP1 as a key mediator for the oncogenic gain-of-function activities of mutant p53 (mutp53) in cancer. In Akt-hyperactive cancer, TopBP1 forms oligomers and represses E2F1-dependent apoptosis. Here we perform a molecular docking screening and identify a lead compound, calcein, capable of blocking TopBP1 oligomerization and p53 binding, [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude suggère l'intérêt d'une stratégie basée sur l'inhibition d'une déméthylase (JMJD3) pour le traitement des patients pédiatriques atteints d'un gliome du pont cérébral présentant la mutation K27M de l'histone H3.3

Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma

Hashizume, Rintaro ; Andor, Noemi ; Ihara, Yuichiro ; Lerner, Robin ; Gan, Haiyun ; Chen, Xiaoyue ; Fang, Dong ; Huang, Xi ; Tom, Maxwell W. ; Ngo, Vy ; Solomon, David ; Mueller, Sabine ; Paris, Pamela L. ; Zhang, Zhiguo ; Petritsch, Claudia ; Gupta, Nalin ; Waldman, Todd A. ; James, C. David

Pediatric brainstem gliomas often harbor oncogenic K27M mutation of histone H3.3. Here we show that GSKJ4 pharmacologic inhibition of K27 demethylase JMJD3 increases cellular H3K27 methylation in K27M tumor cells and demonstrate potent antitumor activity both in vitro against K27M cells and in vivo against K27M xenografts. Our results demonstrate that increasing H3K27 methylation by inhibiting K27 demethylase is a valid therapeutic strategy for treating K27M-expressing brainstem glioma.

Menée in vitro et in vivo, cette étude met évidence l'activité antitumorale du foretinib, un inhibiteur de MET, dans les tumeurs de médulloblastome métastatique avec activation de la signalisation sonic hedghog

Foretinib is Effective Therapy for Metastatic Sonic Hedgehog Medulloblastoma

Faria, Claudia C ; Golbourn, Brian ; Dubuc, Adrian M. ; Remke, Marc ; Diaz, Roberto J ; Agnihotri, Sameer ; Luck, Amanda ; Sabha, Nesrin ; Olsen, Samantha ; Wu, Xiaochong ; Garzia, Livia ; Ramaswamy, Vijay ; Mack, Stephen C ; Wang, Xin ; Leadley, Michael ; Reynaud, Denis ; Ermini, Leonardo ; Post, Martin ; Northcott, Paul A ; Pfister, Stefan M. ; Croul, Sidney ; Kool, Marcel ; Korshunov, Andrey ; Smith, Christian A ; Taylor, Michael D. ; Rutka, James T

Medulloblastoma is the most common malignant pediatric brain tumor, with metastases present at diagnosis conferring a poor prognosis. Mechanisms of dissemination are poorly understood and metastatic lesions are genetically divergent from the matched primary tumor. Effective and less toxic therapies that target both compartments have yet to be identified. Here we report that the analysis of several large non-overlapping cohorts of medulloblastoma patients reveal MET kinase as a marker of sonic [...]

Mené sur 34 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue la dose maximale tolérée et l'activité antitumorale d'un traitement appelé Atu027, à base de petits ARN-interférents inhibant l'expression de la protéine kinase N3 dans l'endothélium vasculaire

First-in-Human Phase I Study of the Liposomal RNA Interference Therapeutic Atu027 in Patients With Advanced Solid Tumors

Schultheis, Beate ; Strumberg, Dirk ; Santel, Ansgar ; Vank, Christiane ; Gebhardt, Frank ; Keil, Oliver ; Lange, Christian ; Giese, Klaus ; Kaufmann, Jörg ; Khan, Michael ; Drevs, Joachim

Purpose : Atu027 is a novel liposomal RNA interference therapeutic that includes a short-interfering RNA (siRNA), which silences expression of protein kinase N3 in the vascular endothelium. Atu027 has previously been shown to inhibit local tumor invasion as well as lymph node and pulmonary metastasis in mouse cancer models. This first-in-human study aimed to assess the safety, tolerability, and pharmacokinetics of Atu027 while evaluating therapeutic effects on both primary tumors and metastatic [...]

Mené sur 36 patients atteints d'une tumeur solide réfractaire aux traitements existants, cet essai de phase I évalue la dose maximale tolérée et l'activité antitumorale d'un anticorps monoclonal (MORAb-004) conçu pour cibler l'endosialine, une protéine exprimée à la surface des cellules mésenchymateuses

A First-in-human Phase I Study of MORAb-004, a Monoclonal Antibody to Endosialin in Patients with Advanced Solid Tumors

Diaz, Luis A. ; Coughlin, Christina M ; Weil, Susan C. ; Fischel, Jean ; Gounder, Mrinal M. ; Lawrence, Susan ; Azad, Nilofer A ; OShannessy, Daniel ; Grasso, Luigi ; Wustner, Jason ; Ebel, Wolfgang ; Carvajal, Richard

PURPOSE Endosialin (TEM-1, CD248) is a protein expressed on the surface of activated mesenchymal cells, including certain subsets of tumors. Pre-clinical models suppressing endosialin function have shown antitumor activity. A humanized monoclonal antibody, MORAb-004, was engineered to target endosialin and is the first agent in clinical development for this mesenchymal cell target. PATIENTS AND METHODS This first-in-human, open-label, Phase 1 study recruited patients with treatment-refractory [...]

Menée en Allemagne sur 189 patients d'âge supérieur à 60 ans et atteints d'un lymphome diffus à grandes cellules B, cette étude évalue l'efficacité de l'allongement de la durée d'administration du rituximab en complément d'une chimiothérapie combinant cyclophosphamide, doxorubicine, vincristine et prednisone

Optimization of Rituximab for the Treatment of Diffuse Large B-Cell Lymphoma (II): Extended Rituximab Exposure Time in the SMARTE-R-CHOP-14 Trial of the German High-Grade Non-Hodgkin Lymphoma Study Group

Pfreundschuh, Michael ; Poeschel, Viola ; Zeynalova, Samira ; Hänel, Mathias ; Held, Gerhard ; Schmitz, Norbert ; Viardot, Andreas ; Dreyling, Martin H. ; Hallek, Michael ; Mueller, Carsten ; Wiesen, Martin H.J. ; Witzens-Harig, Mathias ; Truemper, Lorenz ; Keller, Ulrich ; Rixecker, Tanja ; Zwick, Carsten ; Murawski, Niels

Purpose : To study pharmacokinetics, toxicity, and efficacy of prolonged rituximab exposure in elderly patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods : In the SMARTE-R-CHOP-14 trial, rituximab 375 mg/m2 was administered, together with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone on a 14-day schedule (6×R-CHOP-14), on days −4, 0, 10, 29, 57, 99, 155, and 239. Pharmacokinetics and outcome were to be compared with those of [...]

Mené en Europe sur 91 patients atteints d'un myélome multiple et éligibles à une greffe autologue de cellules souches, cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse complète, d'une combinaison carfilzomib, thalidomide et dexaméthase en traitement d'induction/consolidation (durée médiane de suivi : 23 mois)

Phase 2 study of carfilzomib, thalidomide and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma

Sonneveld, Pieter ; Asselbergs, Emilie ; Zweegman, Sonja ; van der Holt, Bronno ; Kersten, Marie Jose ; Vellenga, Edo ; van Marwijk-Kooy, Marinus ; Broyl, Annemiek ; de Weerdt, Okke ; Lonergan, Sarah ; Palumbo, Antonio ; Lokhorst, Henk

This multicenter phase 2 study of the European Myeloma Network investigated the combination of carfilzomib, thalidomide, and dexamethasone (KTd) as induction/consolidation therapy for transplant-eligible patients with previously untreated multiple myeloma (N=91). During KTd induction therapy, patients received 4 cycles of carfilzomib 20/27 mg/m2 (n=50), 20/36 mg/m2 (n=20), 20/45 mg/m2 (n=21), or 20/56 mg/m2 (n=20) on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle; thalidomide 200 mg on days [...]

Mené au Japon sur 40 patients atteints d'un carcinome du thymus de stade avancé, cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement combinant carboplatine et paclitaxel

A multicenter phase II study of carboplatin and paclitaxel for advanced thymic carcinoma: WJOG4207 L

Hirai, F. ; Yamanaka, T. ; Taguchi, K. ; Daga, H. ; Ono, A. ; Tanaka, K. ; Kogure, Y. ; Shimizu, J. ; Kimura, T. ; Fukuoka, J. ; Iwamoto, Y. ; Sasaki, H. ; Takeda, K. ; Seto, T. ; Ichinose, Y. ; Nakagawa, K. ; Nakanishi, Y.

Background : Thymic carcinoma (TC) is an exceptionally rare tumor, which has a very poor prognosis differing from thymoma. Till date, there has been no report of any results of clinical trials focusing on TC. The role of non-anthracycline-based chemotherapy has not been elucidated since the previous studies included a relatively small number of TC patients. This single-arm study evaluated carboplatin and paclitaxel (CbP) in chemotherapy-naive patients with advanced TC. Patients and methods : [...]

Mené sur 583 patients atteints d'un cancer avancé du poumon non à petites cellules, cet essai international de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'ajout de figitumumab à l'erlotinib

Randomized, phase III trial of figitumumab in combination with erlotinib versus erlotinib alone in patients with non-adenocarcinoma non-small cell lung cancer

Scagliotti, G. V. ; Bondarenko, I. ; Blackhall, F. ; Barlesi, F. ; Hsia, T-C. ; Jassem, J. ; Milanowski, J. ; Popat, S. ; Sanchez-Torres, J. M. ; Novello, S. ; Benner, R. J. ; Green, S. ; Molpus, K. ; Soria, J-C. ; Shepherd, F. A.

Background : Figitumumab (CP-751,871) is a fully human IgG2 monoclonal antibody that inhibits the insulin-like growth factor 1 receptor. This multicenter, randomized, phase III study investigated the efficacy of figitumumab plus erlotinib compared with erlotinib alone in patients with pretreated, non-small cell lung cancer (NSCLC). Patients and methods : Patients (stage IIIB/IV or recurrent disease with non-adenocarcinoma histology) who had previously received at least one platinum-based [...]

Mené en France sur 284 patients atteints d'un cancer colorectal présentant des métastases résécables, cet essai randomisé multicentrique de phase III compare l'efficacité, du point de vue de la survie sans maladie à 2 ans, et la toxicité de 2 schémas de chimiothérapie, par FOLFOX4 ou par FOLFOX7 puis FOLFIRI

FOLFOX4 versus sequential dose-dense FOLFOX7 followed by FOLFIRI in patients with resectable metastatic colorectal cancer (MIROX): a pragmatic approach to chemotherapy timing with perioperative or postoperative chemotherapy from an open-label, randomised phase 3 trial

Hebbar, M. ; Chibaudel, B. ; André, T. ; Mineur, L. ; Smith, D. ; Louvet, C. ; Dutel, J.L. ; Ychou, M. ; Legoux, J.L. ; Mabro, M. ; Faroux, R. ; Auby, D. ; Brusquant, D. ; Khalil, A. ; Truant, S. ; Hadengue, A. ; Dalban, C. ; Gayet, B. ; Paye, F. ; Pruvot, F.R. ; Bonnetain, F. ; de Gramont, A.

Background : Perioperative FOLFOX4 (oxaliplatin plus 5-fluorouracil/leucovorin) chemotherapy is the current standard in patients with resectable metastases from colorectal cancer (CRC). We aimed to determine whether a sequential chemotherapy with dose-dense oxaliplatin (FOLFOX7) and irinotecan (FOLFIRI; irinotecan plus 5-fluorouracil/leucovorin) is superior to FOLFOX4. The chemotherapy timing was not imposed, and was perioperative or postoperative. Patients and methods : In this open-label, [...]

A partir d'une revue de la littérature publiée entre janvier 2011 et décembre 2013, cette étude passe en revue les méthodes statistiques utilisées pour évaluer des combinaisons de traitements anticancéreux dans des essais cliniques de phase I

Designs of drug-combination phase I trials in oncology: a systematic review of the literature

Riviere, M-K. ; Le Tourneau, C. ; Paoletti, X. ; Dubois, F. ; Zohar, S.

Background : Combining several anticancer agents can increase the overall anti-tumor action, but at the same time, it can also increase the overall observed toxicity. Adaptive dose-escalation designs for drug combinations have recently emerged as an attractive alternative to algorithm-based designs, and they seem more effective in combination recommendations. These methods are not used in practice currently. Our aim is to describe international scientific practices in the setting of phase I [...]

A partir de données portant sur 83 patients inclus dans 3 essais cliniques de phase I, cette étude évalue l'intérêt d'une nouvelle approche d'analyse de la toxicité des cycles de traitements

A new approach to integrate toxicity grade and repeated treatment cycles in the analysis and reporting of phase I dose-finding trials

Doussau, A. ; Thiébaut, R. ; Geoerger, B. ; Schoffski, P. ; Floquet, A. ; Le Deley, M.C. ; Mathoulin-Pelissier, S. ; Rizzo, E. ; Fumoleau, P. ; Le Tourneau, C. ; Paoletti, X.

Background : Safety assessment beyond the dose-limiting toxicity evaluation period provides relevant information to define the recommended phase II dose (RP2D) of a new treatment. We retrospectively analyzed three phase I trials to illustrate two indicators: per cycle probability of graded toxicity and cumulative probability of severe toxicity over the treatment period. Patients and methods : Data were collected from two continual reassessment method (CRM) trials (T1: aviscumine in solid tumors [...]

Menée auprès de 300 cliniciens, cet essai randomisé évalue, du point de vue de leur interprétation du bénéfice thérapeutique, l'effet d'une rédaction présentant, de façon favorable ou neutre dans le résumé de l'article, les résultats d'un essai clinique randomisé

Impact of Spin in the Abstracts of Articles Reporting Results of Randomized Controlled Trials in the Field of Cancer: The SPIIN Randomized Controlled Trial

Boutron, Isabelle ; Altman, Douglas G. ; Hopewell, Sally ; Vera-Badillo, Francisco ; Tannock, Ian ; Ravaud, Philippe

Purpose : We aimed to assess the impact of spin (ie, reporting to convince readers that the beneficial effect of the experimental treatment is greater than shown by the results) on the interpretation of results of abstracts of randomized controlled trials (RCTs) in the field of cancer. Methods : We performed a two-arm, parallel-group RCT. We selected a sample of published RCTs with statistically nonsignificant primary outcome and with spin in the abstract conclusion. Two versions of these [...]

Menée notamment à l'aide d'un modèle murin de lymphome, cette étude évalue l'intérêt d'un assemblage de peptides pour acheminer dans le micro-environnement tumoral des composés ciblant un micro-ARN oncogénique (miR-155)

MicroRNA silencing for cancer therapy targeted to the tumour microenvironment

Cheng, Christopher J. ; Bahal, Raman ; Babar, Imran A. ; Pincus, Zachary ; Barrera, Francisco ; Liu, Connie ; Svoronos, Alexander ; Braddock, Demetrios T. ; Glazer, Peter M. ; Engelman, Donald M. ; Saltzman, W. Mark ; Slack, Frank J.

MicroRNAs are short non-coding RNAs expressed in different tissue and cell types that suppress the expression of target genes. As such, microRNAs are critical cogs in numerous biological processes, and dysregulated microRNA expression is correlated with many human diseases. Certain microRNAs, called oncomiRs, play a causal role in the onset and maintenance of cancer when overexpressed. Tumours that depend on these microRNAs are said to display oncomiR addiction. Some of the most effective [...]

Cet article passe en revue les défis et les controverses concernant la prise en charge du cancer du pénis

Challenges and controversies in the management of penile cancer

Shabbir, Majid ; Kayes, Oliver ; Minhas, Suks

Penile cancer is a rare disease, accounting for ~1% of all malignancies in men. Poor awareness of the condition among the public and clinicians often causes long delays in diagnosis and treatment, which may result in the development of advanced disease that might require extensive and emasculating surgery. In the UK, the development of supraregional penile cancer centres has pooled resources and expertise, which has led to considerable improvements in our understanding and management of this [...]

Menée à l'aide d'échantillons tumoraux prélevés sur des patients atteints d'un cancer du poumon, cette étude évalue l'intérêt d'une plateforme pharmacogénomique in vitro pour identifier rapidement des combinaisons de traitements susceptibles de surmonter une résistance thérapeutique

Patient-derived models of acquired resistance can identify effective drug combinations for cancer

Crystal, Adam S. ; Shaw, Alice T. ; Sequist, Lecia V. ; Friboulet, Luc ; Niederst, Matthew J. ; Lockerman, Elizabeth L. ; Frias, Rosa L. ; Gainor, Justin F. ; Amzallag, Arnaud ; Greninger, Patricia ; Lee, Dana ; Kalsy, Anuj ; Gomez-Caraballo, Maria ; Elamine, Leila ; Howe, Emily ; Hur, Wooyoung ; Lifshits, Eugene ; Robinson, Hayley E. ; Katayama, Ryohei ; Faber, Anthony C. ; Awad, Mark M. ; Ramaswamy, Sridhar ; Mino-Kenudson, Mari ; Iafrate, A. John ; Benes, Cyril H. ; Engelman, Jeffrey A.

Targeted cancer therapies have produced substantial clinical responses, but most tumors develop resistance to these drugs. Here, we describe a pharmacogenomic platform that facilitates rapid discovery of drug combinations that can overcome resistance. We established cell culture models derived from biopsy samples of lung cancer patients whose disease had progressed while on treatment with EGFR or ALK tyrosine kinase inhibitors and then subjected these cells to genetic analyses and a [...]