Mené sur 166 patients atteints d'un cancer de la prostate traité par radiothérapie, cet essai de phase II évalue l'efficacité du butyrate de sodium en lavement rectal pendant et après le traitement pour réduire le risque de rectite liée aux rayonnements ionisants

Daily Sodium Butyrate Enema for the Prevention of Radiation Proctitis in Prostate Cancer Patients Undergoing Radical Radiation Therapy: Results of a Multicenter Randomized Placebo-Controlled Dose-Finding Phase 2 Study

Maggio, Angelo ; Magli, Alessandro ; Rancati, Tiziana ; Fiorino, Claudio ; Valvo, Francesca ; Fellin, Giovanni ; Ricardi, Umberto ; Munoz, Fernando ; Cosentino, Dorian ; Cazzaniga, Luigi Franco ; Valdagni, Riccardo ; Vavassori, Vittorio

To evaluate the efficacy of sodium butyrate enemas (NABUREN) in prostate cancer radiation therapy (RT) in reducing the incidence, severity, and duration of acute RT-induced proctitis. 166 patients, randomly allocated to 1 of 4 groups (rectal sodium butyrate 1 g, 2 g, or 4 g daily or placebo), were treated with NABUREN during and 2 weeks after RT. The grade of proctitis was registered in a daily diary. The correlation between NABUREN and proctitis was investigated through χ2 statistics. The [...]

Mené sur 204 patients atteints d'un cancer colorectal traité entre juillet 2008 et avril 2012, cet essai multicentrique évalue le bénéfice, en termes de réduction des symptômes de fatigue physique un mois après le traitement, de durée d'hospitalisation, de réduction des complications et de récupération des fonctions physiques, d'une résection laparoscopique par rapport à une intervention chirurgicale par voie ouverte

Multicenter Randomized Controlled Trial of Conventional Versus Laparoscopic Surgery for Colorectal Cancer Within an Enhanced Recovery Programme: EnROL

Kennedy, Robin H. ; Francis, E. Anne ; Wharton, Rose ; Blazeby, Jane M. ; Quirke, Philip ; West, Nicholas P. ; Dutton, Susan J.

Purpose : Laparoscopic resection and a multimodal approach known as an enhanced recovery program (ERP) have been major changes in colorectal perioperative care that have improved clinical outcomes for colorectal cancer resection. EnROL (Enhanced Recovery Open Versus Laparoscopic) is a multicenter randomized controlled trial examining whether the benefits of laparoscopy still exist when open surgery is optimized within an ERP. Patients and Methods : Adults with colorectal cancer suitable for [...]

Cet article passe en revue les travaux récents suggérant l'intérêt de cibler la protéine MELK pour le traitement de divers types de cancer

Maternal Embryonic Leucine Zipper Kinase: Key Kinase for Stem Cell Phenotype in Glioma and Other Cancers

Ganguly, Ranjit ; Hong, Christopher S. ; Smith, Luke G.F. ; Kornblum, Harley I. ; Nakano, Ichiro

Maternal embryonic leucine zipper kinase (MELK) is a member of the snf1/AMPK family of protein serine/threonine kinases that has recently gained significant attention in the stem cell and cancer biology field. Recent studies suggest that activation of this kinase is tightly associated with extended survival and accelerated proliferation of cancer stem cells (CSC) in various organs. Overexpression of MELK has been noted in various cancers, including colon, breast, ovaries, pancreas, prostate, [...]

Cet article passe en revue les perspectives offertes par des thérapies ciblant les lymphocytes T régulateurs et les cellules myéloïdes suppressives pour le traitement des cancers

Chemotherapeutic Targeting of Cancer-Induced Immunosuppressive Cells

Alizadeh, Darya ; Larmonier, Nicolas

The expansion of immunosuppressive cells represents a cardinal strategy deployed by tumors to escape from detection and elimination by the immune system. Regulatory T lymphocytes (Treg) and myeloid-derived suppressor cells (MDSC), major components of these inhibitory cellular networks, have drawn intense scrutiny in recent years. In patients with cancer and in animal tumor models, these suppressor cells accumulate in the tumor microenvironment, secondary lymphoid tissues, and in the blood. [...]

Menée à l'aide d'un modèle murin de mélanome, cette étude évalue l'activité antitumorale d'un traitement combinant un inhibiteur de BRAF et un traitement anti PD-1 ou anti PD-L1

Response to BRAF inhibition in melanoma is enhanced when combined with immune checkpoint blockade

Cooper, Zachary A ; Juneja, Vikram R ; Sage, Peter T ; Frederick, Dennie T ; Piris, Adriano ; Mitra, Devarati ; Lo, Jennifer A ; Hodi, F Stephen ; Freeman, Gordon J ; Bosenberg, Marcus W. ; McMahon, Martin ; Flaherty, Keith T ; Fisher, David E. ; Sharpe, Arlene H. ; Wargo, Jennifer A

BRAF targeted therapy results in objective responses in the majority of patients, however responses are short lived (~6 months). In contrast, treatment with immune checkpoint inhibitors results in a lower response rate, but responses tend to be more durable. BRAF inhibition results in a more favorable tumor microenvironment in patients, with an increase in CD8+ T cell infiltrate and a decrease in immunosuppressive cytokines. However, there is also increased expression of the immunomodulatory [...]

Menée in vitro et in vivo, cette étude suggère l'intérêt d'un antipaludique, la chloroquine, pour le traitement adjuvant d'un adénocarcinome canalaire du pancréas

Chloroquine targets pancreatic cancer stem cells via inhibition of CXCR4 and hedgehog signaling

Balic, Anamarie ; Dræby Sørensen, Morten ; Trabulo, Sara Maria ; Sainz, Bruno ; Cioffi, Michele ; Vieira, Catarina R. ; Miranda-Lorenzo, Irene ; Hidalgo, Manuel ; Kleeff, Joerg ; Erkan, Mert ; Heeschen, Christopher

Pancreatic ductal adenocarcinoma is one of the deadliest carcinomas and is characterized by highly tumorigenic and metastatic cancer stem cells (CSCs). CSCs evade available therapies, which preferentially target highly proliferative and more differentiated progenies leaving behind CSCs as a putative source for disease relapse. Thus, to identify potentially more effective treatment regimens we screened established and new compounds for their ability to eliminate CSCs in primary pancreatic cancer [...]

Cet article passe en revue les travaux récents sur les traitements anti-androgènes pour les patients atteints d'un cancer de la prostate après une radiothérapie ou une prostatectomie radicale

Concept and viability of androgen annihilation for advanced prostate cancer

Mohler, James L.

There remains no standard of care for patients with a rising prostate-specific antigen level after radical prostatectomy or radiotherapy but who have no radiographic metastases, even though this is the second largest group of patients with prostate cancer (CaP) in the United States. Androgen deprivation therapy (ADT) may cure some men with advanced CaP based on single-institution series and a randomized clinical trial of immediate versus delayed ADT for men found to have pelvic lymph node [...]

Menée in vitro, cette étude suggère l'intérêt de l'inhibition de SLC6A6 pour le traitement d'un cancer colorectal réfractaire

Role of SLC6A6 in promoting the survival and multidrug resistance of colorectal cancer

Yasunaga, Masahiro ; Matsumura, Yasuhiro

The treatment of colorectal cancer (CRC) might be improved by the identification of a signalling pathway that could be targeted with novel therapeutics. The results of this study indicate that the taurine transporter SLC6A6 is highly expressed in CRC cells compared with normal colonocytes. SLC6A6 knockdown (KD) attenuated cell survival and was accompanied by enhanced drug sensitivity to 5-fluorouracil (5-FU), doxycycline (DOX) and SN-38. Both the population frequency of the side population (SP) [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes de cancer colorectal, cette étude met en évidence le rôle joué par la protéine PUMA dans la régulation de la sensibilité des cellules tumorales au regorafenib

Regorafenib inhibits colorectal tumor growth through PUMA-mediated apoptosis

Chen, Dongshi ; Wei, Liang ; Yu, Jian ; Zhang, Lin

Purpose: Regorafenib, a multi-kinase inhibitor targeting the Ras/Raf/MEK/ERK pathway, has recently been approved for the treatment of metastatic colorectal cancer (CRC). However, the mechanisms of action of regorafenib in CRC cells have been unclear. We investigated how regorafenib suppresses CRC cell growth and potentiates effects of other chemotherapeutic drugs. Experimental Design: We determined whether and how regorafenib induces the expression of PUMA, a p53 target and a critical mediator [...]

Cet article passe en revue les travaux récents en immunothérapie des gliomes

Immunotherapy for Brain Cancer: Recent Progress and Future Promise

Jackson, Christopher M. ; Lim, Michael ; Drake, Charles G.

Immunotherapy is emerging as the newest pillar of cancer treatment, with the potential to assume a place alongside surgical debulking, radiation therapy, and chemotherapy. Early experiences with antitumor vaccines demonstrated the feasibility and potential efficacy of this approach and newer agents, such as immune checkpoint blocking antibodies and modern vaccine platforms, have ushered in a new era. These efforts are headlined by work in melanoma, prostate cancer, and renal cell carcinoma; [...]

Menée sur des lignées cellulaires et à l'aide d'un modèle murin, cette étude met en évidence l'intérêt de nanoparticules à base de poly(bêta-amino ester) biodégradable pour acheminer de l'ADN à l'intérieur des tumeurs de glioblastomes

Biodegradable Polymeric Nanoparticles Show High Efficacy and Specificity at DNA Delivery to Human Glioblastoma in Vitro and in Vivo

Guerrero-Cázares, Hugo ; Tzeng, Stephany Y. ; Young, Noah P. ; Abutaleb, Ameer O. ; Quiñones-Hinojosa, Alfredo ; Green, Jordan J.

Current glioblastoma therapies are insufficient to prevent tumor recurrence and eventual death. Here, we describe a method to treat malignant glioma by nonviral DNA delivery using biodegradable poly(?-amino ester)s (PBAEs), with a focus on the brain tumor initiating cells (BTICs), the tumor cell population believed to be responsible for the formation of new tumors and resistance to many conventional therapies. We show transfection efficacy of >60% and low biomaterial-mediated cytotoxicity in [...]

Cet article présente les résultats de l'étude de faisabilité, menée sur 100 patients atteints d'un cancer réfractaire, de l'essai français SHIVA visant à comparer l'efficacité de thérapies ciblées, prescrites sur la base d'une analyse moléculaire des tumeurs, et de chimiothérapies conventionnelles

Randomised proof-of-concept phase II trial comparing targeted therapy based on tumour molecular profiling vs conventional therapy in patients with refractory cancer: results of the feasibility part of the SHIVA trial

Le Tourneau, C. ; Paoletti, X. ; Servant, N. ; Bieche, I. ; Gentien, D. ; Rio Frio, T. ; Vincent-Salomon, A. ; Servois, V. ; Romejon, J. ; Mariani, O. ; Bernard, V. ; Huppe, P. ; Pierron, G. ; Mulot, F. ; Callens, C. ; Wong, J. ; Mauborgne, C. ; Rouleau, E. ; Reyes, C. ; Henry, E. ; Leroy, Q. ; Gestraud, P. ; La Rosa, P. ; Escalup, L. ; Mitry, E. ; Tredan, O. ; Delord, J. P. ; Campone, M. ; Goncalves, A. ; Isambert, N. ; Gavoille, C. ; Kamal, M.

Background: The SHIVA trial is a multicentric randomised proof-of-concept phase II trial comparing molecularly targeted therapy based on tumour molecular profiling vs conventional therapy in patients with any type of refractory cancer. Results of the feasibility study on the first 100 enrolled patients are presented. Methods: Adult patients with any type of metastatic cancer who failed standard therapy were eligible for the study. The molecular profile was performed on a mandatory biopsy, and [...]

Mené sur 49 patients pédiatriques atteints d'une leucémie myéloïde aiguë récidivante ou réfractaire, cet essai de phase I/II évalue l'efficacité et la toxicité d'un traitement combinant clofarabine et cytarabine

AAML0523: A report from the Children's Oncology Group on the efficacy of clofarabine in combination with cytarabine in pediatric patients with recurrent acute myeloid leukemia

Cooper, Todd M. ; Alonzo, Todd A. ; Gerbing, Robert B. ; Perentesis, John P. ; Whitlock, James A. ; Taub, Jeffrey W. ; Horton, Terzah M. ; Gamis, Alan S. ; Meshinchi, Soheil ; Loken, Michael R. ; Razzouk, Bassem I.

BACKGROUND : The discovery of new, effective non–anthracycline-based reinduction regimens for children with recurrent acute myeloid leukemia (AML) is critical. In this phase 1/2 study, the tolerability and overall response rate of clofarabine in combination with cytarabine was investigated in children with recurrent/refractory AML. METHODS : AAML0523 enrolled 49 children with AML in first recurrence or who were refractory to induction therapy. The study consisted of a dose-finding phase (9 [...]

Cet article passe en revue les travaux récents sur les traitements de métastases osseuses chez les patients atteints d'un cancer de la prostate

Recent advances in bone-targeted therapies of metastatic prostate cancer

Deng, Xiyun ; He, Guangchun ; Liu, Junwen ; Luo, Feijun ; Peng, Xiaoning ; Tang, Shigang ; Gao, Zhiyong ; Lin, Qinlu ; Keller, Jill M. ; Yang, Tao ; Keller, Evan T.

Prostate cancer is one of the most common malignancies affecting men worldwide, with bone being the most common site of metastasis in patients that progress beyond organ confinement. Bone metastases are virtually incurable and result in significant disease morbidity and mortality. Bone provides a unique microenvironment whose local interactions with tumor cells offer novel targets for therapeutic interventions. Several attractive molecules or pathways have been identified as new potential [...]

Mené sur 296 patientes atteintes d'un cancer du sein triplement négatif ou HER2+ non métastatique, cet essai de phase II évalue l'efficacité, du point de vue du taux de patientes avec réponse pathologique complète, et la toxicité de l'ajout de carboplatine à un traitement néoadjuvant

Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial

von Minckwitz, Gunter ; Schneeweiss, Andreas ; Loibl, Sibylle ; Salat, Christoph ; Denkert, Carsten ; Rezai, Mahdi ; Blohmer, Jens U. ; Jackisch, Christian ; Paepke, Stefan ; Gerber, Bernd ; Zahm, Dirk M. ; Kümmel, Sherko ; Eidtmann, Holger ; Klare, Peter ; Huober, Jens ; Costa, Serban ; Tesch, Hans ; Hanusch, Claus ; Hilfrich, Jörn ; Khandan, Fariba ; Fasching, Peter A. ; Sinn, Bruno V. ; Engels, Knut ; Mehta, Keyur ; Nekljudova, Valentina ; Untch, Michael

Background : Preclinical data suggest that triple-negative breast cancers are sensitive to interstrand crosslinking agents, and that synergy may exist for the combination of a taxane, trastuzumab, and a platinum salt for HER2-positive breast cancer. We therefore aimed to assess the efficacy of the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive breast cancer. Methods : Patients with previously untreated, non-metastatic, stage II—III, triple-negative breast [...]

A partir d'une revue systématique de la littérature publiée entre janvier 2009 et octobre 2012 (16 essais identifiés), cet article présente des recommandatiosn pour le traitement des patientes atteintes d'un cancer du sein HER2+ de stade avancé

Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline

Giordano, Sharon H. ; Temin, Sarah ; Kirshner, Jeffrey J. ; Chandarlapaty, Sarat ; Crews, Jennie R. ; Davidson, Nancy E. ; Esteva, Francisco J. ; Gonzalez-Angulo, Ana M. ; Krop, Ian ; Levinson, Jennifer ; Lin, Nancy U. ; Modi, Shanu ; Patt, Debra A. ; Perez, Edith A. ; Perlmutter, Jane ; Ramakrishna, Naren ; Winer, Eric P.

Purpose : To provide evidence-based recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2) –positive advanced breast cancer. Methods : The American Society of Clinical Oncology convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic literature review from January 2009 to October 2012. Outcomes of interest included overall survival, [...]

A partir d'une revue systématique de la littérature (25 articles analysés, portant au total sur 761 patients), cette étude évalue l'efficacité et la toxicité des chimiothérapies de deuxième ligne pour le traitement d'un cancer des voies biliaires de stade avancé

Second-line chemotherapy in advanced biliary cancer: a systematic review

Lamarca, Angela ; Hubner, Richard A. ; Ryder, W. David ; Valle, Juan W.

Background : The randomized NCRN phase III ABC-02 trial provided level-A evidence for first-line chemotherapy with cisplatin and gemcitabine combination in advanced biliary cancer (ABC). This systematic literature review aims to evaluate the level of evidence for the use of second-line chemotherapy for patients with ABC in terms of overall survival, response, toxicity and quality of life. Methods : Eligible studies were identified using MEDLINE, ASCO, ESMO and the World Gastrointestinal [...]

Menée in vitro et à l'aide d'une xénogreffe de carcinome gastrique humain sur un modèle murin, cette étude évalue les effets antitumoraux d'une immunophotothérapie utilisant un anticorps monoclonal humain ciblant l'antigène-carcinoembryonnaire et conjugué à un agent sensibilisant les cellules tumorales aux rayonnements dont la longueur d'onde est proche de l'infra-rouge

Potent and specific antitumor effect of CEA-targeted photoimmunotherapy

Shirasu, Naoto ; Yamada, Hiromi ; Shibaguchi, Hirotomo ; Kuroki, Motomu ; Kuroki, Masahide

Conventional photodynamic therapy (PDT) for cancer is limited by the insufficient efficacy and specificity of photosensitizers. We herein describe a highly effective and selective tumor-targeted PDT using a near-infrared (NIR) photosensitizer, IRDye700DX, conjugated to a human monoclonal antibody (Ab) specific for carcinoembryonic antigen (CEA). The antitumor effects of this Ab-assisted PDT, called photoimmunotherapy (PIT), were investigated in vitro and in vivo. The Ab-IRDye conjugate induced [...]

Menée à partir de données médicales portant sur 100 patients atteints d'un carcinome du canal anal, cette étude évalue l'efficacité, du point de vue du taux de contrôle à 5 et 10 ans, et la toxicité d'une radiothérapie curative avec ou sans chimiothérapie

External Beam Radiotherapy ± Chemotherapy in the Treatment of Anal Canal Cancer: A Single-Institute Long-Term Experience on 100 Patients

De Bari, Berardino ; Buglione, Michela ; Maddalo, Marta ; Lestrade, Laëtitia ; Spiazzi, Luigi ; Vitali, Paola ; Barbera, Fernando ; Magrini, Stefano M.

One-hundred patients treated with curative radiotherapy (RT) ± chemotherapy (CT) for an anal canal carcinoma (T1–4N0–3M0) were retrospectively analyzed. Five- and 10-year local control (LC) rates were 73% and 67%, respectively. Acute and late G3–G4 toxicity rates were 32% and 12%, respectively. Two patients underwent a colostomy for a G4 anal toxicity. This study confirms the outcomes of RT ± CT in the treatment of anal canal cancer. Concomitant CT and LC statistically influenced Overall [...]

Mené sur 1 608 patients atteints d'un cancer du rectum de stade II ou III traité entre 2004 et 2010, cet essai compare, du point de vue du taux de réponse pathologique complète ou du taux de chirurgie préservant le sphincter, l'intérêt d'ajouter à une radiothérapie pré-opératoire une chimiothérapie concomitante, à base de fluorouracile en perfusion intraveineuse continue ou de capécitabine orale, en combinaison ou non avec l'oxaliplatine

Capecitabine and Oxaliplatin in the Preoperative Multimodality Treatment of Rectal Cancer: Surgical End Points From National Surgical Adjuvant Breast and Bowel Project Trial R-04

O’Connell, Michael J. ; Colangelo, Linda H. ; Beart, Robert W. ; Petrelli, Nicholas J. ; Allegra, Carmen J. ; Sharif, Saima ; Pitot, Henry C. ; Shields, Anthony F. ; Landry, Jerome C. ; Ryan, David P. ; Parda, David S. ; Mohiuddin, Mohammed ; Arora, Amit ; Evans, Lisa S. ; Bahary, Nathan ; Soori, Gamini S. ; Eakle, Janice ; Robertson, John M. ; Moore, Dennis F. ; Mullane, Michael R. ; Marchello, Benjamin T. ; Ward, Patrick J. ; Wozniak, Timothy F. ; Roh, Mark S. ; Yothers, Greg ; Wolmark, Norman

Purpose : The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT. Patients and Methods : Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily [...]

Cet article présente des recommandations rédigées par un groupe d'experts de l'American Society of Clinical Oncology pour la prise en charge et le traitement de métastases cérébrales chez des patientes atteintes d'un cancer du sein HER2+

Recommendations on Disease Management for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases: American Society of Clinical Oncology Clinical Practice Guideline

Ramakrishna, Naren ; Temin, Sarah ; Chandarlapaty, Sarat ; Crews, Jennie R. ; Davidson, Nancy E. ; Esteva, Francisco J. ; Giordano, Sharon H. ; Gonzalez-Angulo, Ana M. ; Kirshner, Jeffrey J. ; Krop, Ian ; Levinson, Jennifer ; Modi, Shanu ; Patt, Debra A. ; Perez, Edith A. ; Perlmutter, Jane ; Winer, Eric P. ; Lin, Nancy U.

Purpose : To provide formal expert consensus–based recommendations to practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2 (HER2) –positive advanced breast cancer. Methods : The American Society of Clinical Oncology (ASCO) convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic review of the literature. When that failed to yield sufficiently [...]

A partir d'une revue systématique de la littérature, cette étude évalue l'efficacité et la toxicité d'un traitement pré-opératoire combinant, de manière séquentielle et/ou concomitante, une chimiothérapie et une radiothérapie du sein entier pour traiter un cancer du sein de stade localement avancé

Primary systemic therapy and whole breast irradiation for locally advanced breast cancer. A systematic review

Kaidar–Person, Orit ; Kuten, Abraham ; Belkacémi, Yazid

The current management of locally advanced breast cancer (LABC) is based on tri-modality treatment including chemotherapy, radiotherapy and surgery. The concept of preoperative concurrent or sequential chemoradiation for LABC was initially reported more than a decade ago; however this concept did not gain popularity because of the low benefit/risk ratio and the lack of strong data supporting the concept. The purpose of the current systematic review was to explore the published data about [...]

Cet article présente les recommandations de l' "European Society for Medical Oncology" concernant le diagnostic et le traitement d'un gliome de haut grade ainsi que le suivi des patients

High-grade glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Stupp, R. ; Brada, M. ; van den Bent, M. J. ; Tonn, J.-C. ; Pentheroudakis, G. ; on behalf of the ESMO Guidelines Working Group

Incidence and epidemiology : The yearly incidence of malignant glioma is ∼3–5/100 000 with a slight predominance in males. Malignant glioma may develop at all ages, with the peak incidence being in the fifth and sixth decades of life [1–3]. Exposure to ionising irradiation has been associated with increased risk of development of glioma, while association with the use of cell phones could not be confirmed in epidemiological studies. Rare hereditary syndromes carry an increased risk for glioma: [...]

Mené sur 17 patients atteints d'un gliome de haut grade récemment diagnostiqué, cet essai de phase I évalue la dose maximale tolérée et la toxicité du sorafénib en combinaison avec une radiothérapie et le témozolomide

Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma

Hottinger, A. F. ; Aissa, A. B. ; Espeli, V. ; Squiban, D. ; Dunkel, N. ; Vargas, M. I. ; Hundsberger, T. ; Mach, N. ; Schaller, K. ; Weber, D. C. ; Bodmer, A. ; Dietrich, P. Y.

Background : Sorafenib (Sb) is a multiple kinase inhibitor targeting both tumour cell proliferation and angiogenesis that may further act as a potent radiosensitizer by arresting cells in the most radiosensitive cell cycle phase. This phase I open-label, noncontrolled dose escalation study was performed to determine the safety and maximum tolerated dose (MTD) of Sb in combination with radiation therapy (RT) and temozolomide (TMZ) in 17 patients with newly diagnosed high-grade glioma. Methods : [...]

Menée par questionnaire auprès de 354 médecins généralistes français, cette étude évalue leur degré de confiance dans les résultats de grands essais cliniques en fonction de la présence de mentions de conflits d'intérêts dans les articles publiés

Reporting funding source or conflict of interest in abstracts of randomized controlled trials, no evidence of a large impact on general practitioners' confidence in conclusions, a three-arm randomized controlled trial

du Vaure, Celine ; Boutron, Isabelle ; Perrodeau, Elodie ; Ravaud, Philippe

BACKGROUND:Systematic reporting of funding sources is recommended in the CONSORT Statement for abstracts. However, no specific recommendation is related to the reporting of conflicts of interest (CoI). The objective was to compare physicians' confidence in the conclusions of abstracts of randomized controlled trials of pharmaceutical treatment indexed in PubMed. METHODS:We planned a three-arm parallel-group randomized trial. French general practitioners (GPs) were invited to participate and [...]

Cet article passe en revue les caractéristiques de cinq modèles animaux pour mener des études précliniques en immunothérapie des glioblastomes

Immunocompetent murine models for the study of glioblastoma immunotherapy

Oh, Taemin ; Fakurnejad, Shayan ; Sayegh, Eli ; Clark, Aaron ; Ivan, Michael ; Sun, Matthew ; Safaee, Michael ; Bloch, Orin ; James, Charles ; Parsa, Andrew

Glioblastoma remains a lethal diagnosis with a 5-year survival rate of less than 10%. (JAMA 352:987-96, 2005) Although immunotherapy-based approaches are capable of inducing detectable immune responses against tumor-specific antigens, improvements in clinical outcomes are modest, in no small part due to tumor-induced immunosuppressive mechanisms that promote immune escape and immuno-resistance. Immunotherapeutic strategies aimed at bolstering the immune response while neutralizing [...]