Menée à l'aide d'un modèle murin de cancer humain du sein, cette étude évalue les effets de champs électriques pulsés d'une durée de 100 nanosecondes sur la croissance tumorale ainsi que leur toxicité sur les tissus sains

Nanosecond Pulsed Electric Fields as A Novel drug free Therapy for Breast Cancer: an in vivo study

Wu, Shan ; Wang, Yu ; Guo, Jinsong ; Chen, Qunzhi ; Zhang, Jue ; Fang, Jing

Abstract : Nanosecond pulsed electric fields (nsPEFs) is a novel non-thermal approach to induce cell apoptosis. NsPEFs has been proven effective in treating several murine tumors, but few studies focus on its efficacy in treating human tumors. To determine if nsPEFs is equally effective in treatment of human breast cancer, 30 human breast cancer tumors across 30 Balb/c (nu/nu) mice were exposed to 720 pulses of 100ns duration, at 4 pulses per second and 30kV/cm. Two weeks after treatment, the [...]

A partir d'une revue systématique de la littérature publiée entre 1946 et 2013 (17 études), cette étude évalue l'intérêt d'interventions sur les ganglions axillaires de patientes atteintes d'un cancer du sein pour réduire la mortalité, la morbidité et le risque de récidive de métastases ganglionnaires axillaires

Axillary node interventions in breast cancer: A systematic review

Rao, R. ; Euhus, D. ; Mayo, H. G. ; Balch, C.

Importance Recent data from clinical trials have challenged traditional thinking about axillary surgery in patients with breast cancer. Objectives : To summarize evidence regarding the role of axillary interventions (surgical and nonsurgical) in breast cancer treatment and to review the association of these axillary interventions with recurrence of axillary node metastases, mortality, and morbidity outcomes in patients with breast cancer. Evidence Review : Ovid MEDLINE (1946–July 2013), [...]

Menée sur 40 patients présentant une dysplasie de la cavité buccale, un carcinome in situ ou un carcinome épidermoïde de la tête et du cou de stade précoce (durée de suivi : 5 à 40 mois), cette étude évalue l'efficacité, du point de vue de la réponse tumorale à 3 mois, et la sécurité d'une thérapie photodynamique à base d'un composé appelé HPPH

Photodynamic Therapy with 3-(1'-hexyloxyethyl) pyropheophorbide a (HPPH) for Cancer of the Oral Cavity

Rigual, Nestor R. ; Shafirstein, Gal ; Cooper, Michele ; Baumann, Heinz ; Bellnier, David A ; Sunar, Ulas ; Tracy, Erin ; Rohrbach, Daniel ; Wilding, Gregory ; Tan, Wei ; Sullivan, Maureen A. ; Merzianu, Mihai ; Henderson, Barbara W

Purpose : The primary objective was to evaluate safety of 3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction. Experimental Design : Patients with histologically proven oral dysplasia, carcinoma in situ (CiS ) or early stage HNSCC were enrolled in two sequentially conducted dose [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels un adénovirus oncolytique génétiquement modifié fait perdre leurs propriétés de cellules souches à certaines cellules de tumeurs solides

A genetically engineered oncolytic adenovirus decoys and lethally traps quiescent cancer stem-like cells into S/G2/M-phases

Yano, Shuya ; Tazawa, Hiroshi ; Hashimoto, Yuuri ; Shirakawa, Yasuhiro ; Kuroda, Shinji ; Nishizaki, Masahiko ; Kishimoto, Hiroyuki ; Uno, Futoshi ; Nagasaka, Takeshi ; Urata, Yasuo ; Kagawa, Shunsuke ; Hoffman, Robert M. ; Fujiwara, Toshiyoshi

Purpose: Since chemo-radiotherapy selectively targets proliferating cancer cells, quiescent cancer stem-like (CS-like) cells are resistant. Mobilization of cell cycle in quiescent leukemia stem cells sensitizes them to cell death signals. However, it is unclear that mobilization of cell cycle can eliminate quiescent CS-like cells in solid cancers. Thus, we explored the use of a genetically engineered telomerase-specific oncolytic adenovirus, OBP-301 to mobilize the cell cycle and kill quiescent [...]

Cet article passe en revue les perspectives offertes par les nanoparticules pour le traitement et le diagnostic des cancers

Nanooncology: The future of cancer diagnosis and therapy

Thakor, Avnesh S. ; Gambhir, Sanjiv S.

In recent years, there has been an unprecedented expansion in the field of nanomedicine with the development of new nanoparticles for the diagnosis and treatment of cancer. Nanoparticles have unique biological properties given their small size and large surface area-to-volume ratio, which allows them to bind, absorb, and carry compounds such as small molecule drugs, DNA, RNA, proteins, and probes with high efficiency. Their tunable size, shape, and surface characteristics also enable them to [...]

Menée in vitro et in vivo, cette étude suggère l'intérêt des inhibiteurs de Src pour surmonter la résistance aux anticorps anti IGF-1R dans le traitement d'un cancer du poumon non à petites cellules ou de la tête et du cou

Combating Resistance to Anti-IGFR Antibody by Targeting the Integrin β3-Src Pathway

Shin, Dong Hoon ; Lee, Hyo-Jong ; Min, Hye-Young ; Choi, Sun Phil ; Lee, Mi-Sook ; Lee, Jung Weon ; Johnson, Faye M. ; Mehta, Kapil ; Lippman, Scott M. ; Glisson, Bonnie S. ; Lee, Ho-Young

Background Several phase II/III trials of anti–insulin-like growth factor 1 receptor (IGF-1R) monoclonal antibodies (mAbs) have shown limited efficacy. The mechanisms of resistance to IGF-1R mAb-based therapies and clinically applicable strategies for overcoming drug resistance are still undefined. Methods IGF-1R mAb cixutumumab efficacy, alone or in combination with Src inhibitors, was evaluated in 10 human head and neck squamous cell carcinoma (HNSCC) and six non–small cell lung cancer [...]

Menée à l'aide de xénogreffes de tumeurs de la tête et du cou, cette étude met en évidence des mécanismes par lesquels les facteurs de croissance des fibroblastes favorisent la résistance au bévacizumab

A Proangiogenic Signature is Revealed in FGF-Mediated Bevacizumab Resistant Head and Neck Squamous Cell Carcinoma

Gyanchandani, Rekha ; Ortega Alves, Marcus V. ; Myers, Jeffrey N. ; Kim, Seungwon

Resistance to antiangiogenic therapies is a critical problem that has limited the utility of antiangiogenic agents in clinical settings. However, the molecular mechanisms underlying this resistance have yet to be fully elucidated. In this study, we established a novel xenograft model of acquired resistance to bevacizumab. To identify molecular changes initiated by the tumor cells, we performed human-specific microarray analysis on bevacizumab-sensitive and -resistant tumors. Efficiency analysis [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en relâchant les contraintes physiques exercées sur le réseau vasculaire tumoral, le losartan, un antagoniste des récepteurs de l'angiotensine 2, favorise l'acheminement des agents cytotoxiques à l'intérieur des tumeurs

Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels

Chauhan, Vikash P. ; Martin, John D. ; Liu, Hao ; Lacorre, Delphine A. ; Jain, Saloni R. ; Kozin, Sergey V. ; Stylianopoulos, Triantafyllos ; Mousa, Ahmed S. ; Han, Xiaoxing ; Adstamongkonkul, Pichet ; Popovic, Zoran ; Huang, Peigen ; Bawendi, Moungi G. ; Boucher, Yves ; Jain, Rakesh K.

Cancer and stromal cells actively exert physical forces (solid stress) to compress tumour blood vessels, thus reducing vascular perfusion. Tumour interstitial matrix also contributes to solid stress, with hyaluronan implicated as the primary matrix molecule responsible for vessel compression because of its swelling behaviour. Here we show, unexpectedly, that hyaluronan compresses vessels only in collagen-rich tumours, suggesting that collagen and hyaluronan together are critical targets for [...]

Menée sur des lignées cellulaires, cette étude met en évidence des mécanismes, liés à la régulation de l'expression de la topoisomérase IIα, permettant de rendre compte de l'inefficacité observée dans les études cliniques évaluant l'ajout de lapatinib et de gefinitib à une chimiothérapie

Treatment With Gefinitib Or Lapatinib Induces Drug Resistance Through Downregulation Of Topoisomerase IIα Expression

Bhosle, Jaishree ; Kiakos, Konstantinos ; Porter, Andrew CG ; Wu, Jenny ; Makris, Andreas ; Hartley, John A. ; Hochhauser, Daniel

The epidermal growth factor receptor (EGFR) is therapeutically targeted by antibodies and small molecules in solid tumours including lung, colorectal and breast cancer. However, chemotherapy remains important and efforts to improve efficacy through combination with targeted agents is challenging. This study examined the effects of short and long durations of exposure to the EGFR and HER2 targeted tyrosine kinase inhibitors (TKIs) gefitinib and lapatinib, on induction of cell death and DNA [...]

Menée sur des lignées cellulaires, à l'aide de xénogreffes et d'échantillons prélevés sur des patients atteints d'une leucémie myéloïde aiguë, cette étude évalue l'activité antitumorale d'un promédicament activé dans des conditions d'hypoxie (TH-302)

Activity of the hypoxia-activated prodrug, TH-302, in preclinical human acute myeloid leukemia (AML) models

Portwood, Scott ; Lal, Deepika ; Hsu, Yung-Chun ; Vargas, Rodrigo ; Johnson, Megan K ; Wetzler, Meir ; Hart, Charles P ; Wang, Eunice S

Purpose: Acute myeloid leukemia (AML) is an aggressive hematological neoplasm. Recent evidence has demonstrated the bone marrow microenvironment in AML patients to be intrinsically hypoxic. Adaptive cellular responses by leukemia cells to survive under low oxygenation also confer chemoresistance. We therefore asked whether therapeutic exploitation of marrow hypoxia via the hypoxia-activated nitrogen mustard prodrug, TH-302, could effectively inhibit AML growth. Experimental Design: We assessed [...]

Menée in vitro et in vivo, cette étude suggère l'intérêt de combiner le crizonitib et la gemcitabine pour le traitement d'un adénocarcinome canalaire du pancréas

Crizotinib inhibits metabolic inactivation of gemcitabine in c-Met-driven pancreatic carcinoma

Avan, Amir ; Caretti, Viola ; Funel, Niccola ; Galvani, Elena ; Maftouh, Mina ; Honeywell, Richard J ; Lagerweij, Tonny ; Van Tellingen, Olaf ; Campani, Daniela ; Fuchs, Dieter ; Verheul, Henk M ; Schuurhuis, Gerrit-Jan ; Boggi, Ugo ; Peters, Godefridus J ; Wurdinger, Thomas ; Giovannetti, Elisa

Pancreatic ductal adenocarcinoma (PDAC) remains a major unsolved health problem. Most drugs that pass preclinical tests fail in these patients, emphasizing the need of improved preclinical models to test novel anticancer strategies. Here we developed four orthotopic mouse models employing primary human PDAC cells genetically engineered to express Firefly- and Gaussia-luciferase, simplifying the ability to monitor tumor growth and metastasis longitudinally in individual animals with MRI and [...]

Cet article passe en revue les travaux récents sur les relations entre la transition épithélio-mésenchymateuse, les cellules souches de cancer du sein et la résistance thérapeutique

Epithelial-to-mesenchymal transition: What is the impact on breast cancer stem cells and drug resistance

Mallini, Paraskevi ; Lennard, Thomas ; Kirby, John ; Meeson, Annette

There is increasing interest in cancer stem cells (CSCs) and their role in cancer progression. Recently, CSCs have been identified in brain, skin, and intestinal tumors and it has been suggested that these CSCs are responsible for tumor growth and metastasis. In breast cancer fatality is often due to the development of metastatic disease (MBC). Almost 30% of early breast cancer patients eventually develop MBC and in 90% of these multi-drug resistance (MDR) occurs. This could be attributed to [...]

Menée sur des lignées cellulaires de tumeurs présentant un gène BRCA1 muté, cette étude met en évidence des mécanismes permettant de rendre compte de l'apparition d'une résistance aux inhibiteurs de PARP et aux sels de platine

Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance

Johnson, Neil ; Johnson, Shawn F. ; Yao, Wei ; Li, Yu-Chen ; Choi, Young-Eun ; Bernhardy, Andrea J. ; Wang, Yifan ; Capelletti, Marzia ; Sarosiek, Kristopher A. ; Moreau, Lisa A. ; Chowdhury, Dipanjan ; Wickramanayake, Anneka ; Harrell, Maria I. ; Liu, Joyce F. ; D’Andrea, Alan D. ; Miron, Alexander ; Swisher, Elizabeth M. ; Shapiro, Geoffrey I.

Breast Cancer Type 1 Susceptibility Protein (BRCA1)-deficient cells have compromised DNA repair and are sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. Despite initial responses, the development of resistance limits clinical efficacy. Mutations in the BRCA C-terminal (BRCT) domain of BRCA1 frequently create protein products unable to fold that are subject to protease-mediated degradation. Here, we show HSP90-mediated stabilization of a BRCT domain mutant BRCA1 protein under PARP [...]

Mené sur 30 patients atteints d'une tumeur stromale gastro-intestinale métastatique et/ou non résécable, cet essai de phase II évalue l'efficacité, du point de vue du taux de contrôle de la maladie à 24 semaines, et la toxicité du dovetinib après l'échec d'un traitement par imatinib et sunitinib

Phase II study of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib

Kang, Y. K. ; Yoo, C. ; Ryoo, B. Y. ; Lee, J. J. ; Tan, E. ; Park, I. ; Park, J. H. ; Choi, Y. J. ; Jo, J. ; Ryu, J. S. ; Ryu, M. H.

Background: This prospective, phase II trial evaluated the efficacy and safety of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours (GISTs) after failure of at least imatinib and sunitinib. Methods: Patients received oral dovitinib, 500 mg once daily, for 5 consecutive days, followed by a 2-day rest, every 28 days. The primary endpoint was disease control rate (DCR; objective response+stable disease (SD)) at 24 weeks, assessed by computed tomography (CT) [...]

Mené sur 42 patients atteints d'un carcinome hépatocellulaire avancé, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du ramucirumab en traitement de première ligne

A Phase II and Biomarker Study of Ramucirumab, a Human Monoclonal Antibody Targeting the VEGF Receptor-2 in Patients with Advanced Hepatocellular Cancer

Zhu, Andrew X. ; Finn, Richard S. ; Mulcahy, Mary ; Gurtler, Jayne ; Sun, Weijing ; Schwartz, Jonathan D. ; Dalal, Rita P ; Joshi, Adarsh ; Hozak, Rebecca R ; Xu, Yihuan ; Ancukiewicz, Marek ; Jain, Rakesh K. ; Nugent, Francis ; Duda, Dan G ; Stuart, Keith

Purpose: To assess the efficacy and safety of the anti-VEGF receptor-2 (VEGFR-2) antibody ramucirumab as first-line therapy in patients with advanced hepatocellular carcinoma (HCC) and explore potential circulating biomarkers. Experimental Design: Adults with advanced HCC and no prior systemic treatment received ramucirumab 8 mg/kg/two weeks until disease progression or limiting toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response [...]

Mené sur 1 074 patients atteints d'un cancer hépatocellulaire, cet essai international de phase III compare l'efficacité, du point de vue de la survie globale, et la toxicité du sunitinib et du sorafenib

Sunitinib Versus Sorafenib in Advanced Hepatocellular Cancer: Results of a Randomized Phase III Trial

Cheng, Ann-Lii ; Kang, Yoon-Koo ; Lin, Deng-Yn ; Park, Joong-Won ; Kudo, Masatoshi ; Qin, Shukui ; Chung, Hyun-Cheol ; Song, Xiangqun ; Xu, Jianming ; Poggi, Guido ; Omata, Masao ; Pitman Lowenthal, Susan ; Lanzalone, Silvana ; Yang, Liqiang ; Lechuga, Maria Jose ; Raymond, Eric

Purpose Open-label, phase III trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer. Patients and Methods Patients were stratified and randomly assigned to receive sunitinib 37.5 mg once per day or sorafenib 400 mg twice per day. Primary end point was overall survival (OS). Results Early trial termination occurred for futility and safety reasons. A total of 1,074 patients were randomly assigned to the study (sunitinib arm, n = 530; sorafenib arm, n [...]

Mené sur 30 patients atteints d'un lymphome récidivant ou réfractaire, cet essai de phase I évalue les doses maximales tolérées d'une combinaison panobinostat-évérolimus et met en évidence une toxicité significative (thrombopénie)

Phase I study of panobinostat plus everolimus in patients with relapsed or refractory lymphoma

Oki, Yasuhiro ; Buglio, Daniela ; Fanale, Michelle A ; Fayad, Luis ; Copeland, Amanda R ; Romaguera, Jorge ; Kwak, Larry W ; Pro, Barbara ; Faria, Silvana de Castro ; Neelapu, Sattva S. ; Fowler, Nathan ; Hagemeister, Fredrick B ; Zhang, Jiexin ; Zhou, Shouhao ; Feng, Lei ; Younes, Anas

Purpose: To evaluate the safety and efficacy of panobinostat plus everolimus in patients with relapsed Hodgkin and non-Hodgkin lymphoma. The concept was supported by the single agent clinical activity of histone deacetylase inhibitors and mTOR inhibitors, and on the in vitro mechanism-based synergistic antiproliferative activity. Experimental Design: This was a phase I study in patients with relapsed or refractory Hodgkin and non-Hodgkin lymphoma using panobinostat orally on [...]

Mené sur 71 patientes atteintes d'un carcinome ovarien réfractaire/résistant aux sels de platine, cet essai de phase II compare l'efficacité, du point de vue du taux de réponse objective, de deux modalités d'administration de l'etirinotecan pegol (tous les 14 ou 21 jours)

Randomized Multicenter Phase II Trial Comparing Two Schedules of Etirinotecan Pegol (NKTR-102) in Women With Recurrent Platinum-Resistant/Refractory Epithelial Ovarian Cancer

Vergote, Ignace B. ; Garcia, Agustin ; Micha, John ; Pippitt, Charles ; Bendell, Johanna ; Spitz, Daniel ; Reed, Nicholas ; Dark, Graham ; Fracasso, Paula M. ; Ibrahim, Emad N. ; Armenio, Vincent A. ; Duska, Linda ; Poole, Chris ; Gennigens, Christine ; Dirix, Luc Y. ; Leung, Abraham C.F. ; Zhao, Carol ; Soufi-Mahjoubi, Raoudha ; Rustin, Gordon

Purpose Etirinotecan pegol (NKTR-102) is a unique, long-acting topoisomerase-I inhibitor with prolonged systemic exposure to SN38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan. This randomized phase II trial investigated two dosing schedules of etirinotecan pegol in patients with platinum-resistant/refractory ovarian carcinoma. Patients and Methods A total of 71 eligible patients were randomly assigned to receive etirinotecan pegol 145 mg/m2 every 14 or 21 days until [...]

Mené sur 12 patients pendant la phase Ib, puis 190 patients pendant la phase II, cet essai évalue l'efficacité et la toxicité du conatumumab, en complément d'une chimiothérapie FOLFOX6 modifiée et de bevacizumab, pour le traitement de première ligne d'un cancer colorectal métastatique

TRAIL receptor agonist conatumumab with modified FOLFOX6 plus bevacizumab for first-line treatment of metastatic colorectal cancer

Fuchs, Charles S. ; Fakih, Marwan ; Schwartzberg, Lee ; Cohn, Allen L. ; Yee, Lorrin ; Dreisbach, Luke ; Kozloff, Mark F. ; Hei, Yong-jiang ; Galimi, Francesco ; Pan, Yang ; Haddad, Vincent ; Hsu, Cheng-Pang ; Sabin, Antony ; Saltz, Leonard

BACKGROUND In patients with previously untreated metastatic colorectal cancer (mCRC), we conducted a phase 1b/randomized phase 2 trial to define the safety, tolerability, and efficacy of mFOLFOX6 plus bevacizumab (mFOLFOX6/bev) with conatumumab, an investigational, fully human monoclonal IgG1 antibody that specifically activates death receptor 5 (DR5). METHODS Twelve patients were enrolled in a phase 1b open-label dose-escalation trial of conatumumab with mFOLFOX6/bev; thereafter, 190 patients [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, puis sur 9 patientes atteintes d'un cancer métastatique du sein HER2+, cet essai de phase Ib/II évalue l'efficacité et la toxicité d'un traitement combinant le pertuzumab et le trastuzumab emtansine (T-DM1)

Dual targeting of HER2-positive cancer with trastuzumab-emtansine (T-DM1) and pertuzumab: critical role for neuregulin blockade in anti-tumor response to combination therapy

Lewis Phillips, Gail D. ; Fields, Carter T. ; Li, Guangmin ; Dowbenko, Don ; Schaefer, Gabriele ; Miller, Kathy D. ; Andre, Fabrice ; Burris, Howard A. ; Albain, Kathy S. ; Harbeck, Nadia ; Diéras, Véronique ; Crivellari, Diana ; Fang, Liang ; Guardino, Ellie ; Olsen, Steven R. ; Crocker, Lisa M. ; Sliwkowski, Mark X.

Purpose: Targeting HER2 with multiple HER2-directed therapies represents a promising area of treatment for HER2-positive cancers. We investigated combining the HER2-directed antibody-drug conjugate trastuzumab emtansine (T-DM1) with the HER2 dimerization inhibitor pertuzumab (Perjeta™). Experimental Design: Drug combination studies with T-DM1 and pertuzumab were performed on cultured tumor cells and in mouse xenograft models of HER2-amplified cancer. In patients with HER2-positive locally [...]

A partir d'une revue systématique de la littérature, cet article analyse l'efficacité et la toxicité de stratégies thérapeutiques combinant le trastuzumab et une deuxième thérapie ciblée (lapatinib, pertuzumab ou T-DM1) chez les patientes atteintes d'un cancer du sein HER2+

A systematic review of dual targeting in HER2-positive breast cancer

Kümler, Iben ; Tuxen, Malgorzata K. ; Nielsen, Dorte Lisbet

Background : Human epidermal growth factor receptor 2 (HER2) is overexpresed in 15–20% of all breast cancers. Treatment with trastuzumab has led to an improved outcome and prolonged survival of HER2-positive breast cancer patients and today the drug is established as standard of care in both the adjuvant and metastatic settings. However, trastuzumab resistance is common and a major focus in the treatment of HER2-positive breast cancer has been developing therapeutic agents to either potentiate [...]

Menée sur des cardiomyocytes humains et à l'aide d'un modèle murin, cette étude évalue l'effet du trastuzumab ou du lapatinib sur la cardiotoxicité de la radiothérapie et d'une anthracycline, la doxorubicine

Radiation- and anthracycline-induced cardiac toxicity and the influence of ErbB2 blocking agents

Seemann, Ingar ; Poele, JohannesA M. ; Song, Ji-Ying ; Hoving, Saske ; Russell, NicolaS ; Stewart, FionaA

In Her2-positive breast cancer patients, inhibition of epidermal growth factor receptor 2 (ErbB2)-signaling is often combined with chemotherapy and radiotherapy. The risk of cardiac toxicity after anthracyclines and radiotherapy is recognized, but little is known about increased risk when these treatments are combined with ErbB2 inhibition. This study investigated whether ErbB2 inhibition increased radiation or anthracycline-induced toxicity. In an in vitro study, human cardiomyocytes were [...]

Menée sur une cohorte de 1 483 patients présentant une malignité myéloïde et devant recevoir une greffe de cellules souches hématopoïétiques, cette étude prospective évalue, du point de vue du risque de récidive et de la survie, la non infériorité du busulfan IV par rapport à une radiothérapie de l'ensemble du corps

Prospective cohort study comparing intravenous busulfan to total body irradiation in hematopoietic cell transplantation

Bredeson, Christopher ; LeRademacher, Jennifer ; Kato, Kazunobu ; DiPersio, John F. ; Agura, Edward ; Devine, Steven M. ; Appelbaum, Frederick R. ; Tomblyn, Marcie R. ; Laport, Ginna G. ; Zhu, Xiaochun ; McCarthy, Philip L. ; Ho, Vincent T. ; Cooke, Kenneth R. ; Armstrong, Elizabeth ; Smith, Angela ; Rizzo, J. Douglas ; Burkart, Jeanne M. ; Pasquini, Marcelo C.

We conducted a prospective cohort study testing the non-inferiority of survival of ablative IV-BU versus ablative TBI-based regimens in myeloid malignancies. 1,483 patients transplanted for myeloid malignancies (IV-BU, N=1025, TBI, N=458) were enrolled. Cohorts were similar with respect to age, gender, race, performance score, disease and disease stage at transplant. Most patients had acute myeloid leukemia (68% IV-BU, 78% TBI). Grafts were primarily peripheral blood (77%) from HLA-matched [...]

Mené sur 52 patients atteints d'un lymphome du système nerveux central récemment diagnostiqué (âge : 30 à 79 ans), cet essai multicentrique de phase II évalue l'efficacité, du point de vue de la survie sans maladie et de la survie globale à long terme, et la neurotoxicité d'un traitement comportant une chimiothérapie d'induction de type R-MPV, une consolidation par radiothérapie du cerveau entier avec réduction de la dose de rayonnements et une chimiothérapie par cytarabine

Rituximab, Methotrexate, Procarbazine, and Vincristine Followed by Consolidation Reduced-Dose Whole-Brain Radiotherapy and Cytarabine in Newly Diagnosed Primary CNS Lymphoma: Final Results and Long-Term Outcome

Morris, Patrick G. ; Correa, Denise D. ; Yahalom, Joachim ; Raizer, Jeffrey J. ; Schiff, David ; Grant, Barbara ; Grimm, Sean ; Lai, Rose K. ; Reiner, Anne S. ; Panageas, Kathy ; Karimi, Sasan ; Curry, Richard ; Shah, Gaurav ; Abrey, Lauren E. ; DeAngelis, Lisa M. ; Omuro, Antonio

Purpose : A multicenter phase II study was conducted to assess the efficacy of rituximab, methotrexate, procarbazine, and vincristine (R-MPV) followed by consolidation reduced-dose whole-brain radiotherapy (rdWBRT) and cytarabine in primary CNS lymphoma. Patients and Methods : Patients received induction chemotherapy with R-MPV (five to seven cycles); those achieving a complete response (CR) received rdWBRT (23.4 Gy), and otherwise, standard WBRT was offered (45 Gy). Consolidation cytarabine [...]

Menée sur deux cohortes de 71 et 40 patients atteints d'un carcinome épidermoïde de la tête et du cou, cette étude transversale analyse les effets d'une chimioradiothérapie adjuvante sur le nombre de lymphocytes T régulateurs s'accumulant au niveau du tissu tumoral et met en évidence leur rôle dans l'apparition d'une récidive

Effects of adjuvant chemoradiotherapy on the frequency and function of regulatory T cells in patients with head and neck cancer

Schuler, Patrick J ; Harasymczuk, Malgorzata ; Schilling, Bastian ; Saze, Zenichiro ; Strauss, Laura ; Lang, Stephan ; Johnson, Jonas T ; Whiteside, Theresa L

Purpose : Regulatory T cells (Treg) accumulate in tumor tissues and the peripheral blood of cancer patients and may persist after therapies. This cross-sectional study examines effects of adjuvant chemo-radiotherapy (CRT) on Treg numbers and function in head and neck squamous cell carcinoma (HNSCC) patients. Experimental Design :The frequency and absolute numbers of CD4+, ATP-hydrolyzing CD4+CD39+ and CD8+ T cells and expression levels of CD39, CD25, TGF-β-associated LAP and GARP on Treg were [...]

Mené sur 39 patients atteints d'un carcinome résécable de l'œsophage ou de la jonction gastro-œsophagienne (âge médian : 64 ans ; 93% d'hommes et 17% de femmes), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse pathologique complète, et la toxicité d'un traitement combinant cetuximab et radiothérapie avant l'intervention chirurgicale

A Phase II Study with Cetuximab and Radiation Therapy for Patients with Surgically Resectable Esophageal and GE Junction Carcinomas: Hoosier Oncology Group G05-92

Becerra, Carlos R. ; Hanna, Nasser ; McCollum, Andrew David ; Becharm, Naftali ; Timmerman, Robert D. ; DiMaio, Michael ; Kesler, Kenneth A. ; Yu, Menggang ; Yan, Tong ; Choy, Hak

Introduction : On the basis of the promising activity of cetuximab and radiation therapy for head and neck cancers, we evaluated the efficacy of this regimen followed by surgery in patients with resectable esophageal cancer. This was a phase II, open-label, single-arm, multicenter study of patients with potentially resectable esophageal cancer. Methods : Patients received two weekly doses of cetuximab followed by weekly cetuximab combined with radiation therapy for 6 weeks. After a 6- to 8-week [...]

Cet article présente une nouvelle méthodologie pour mener des essais de phase III intégrant la mesure, après une courte période de traitement, d'un biomarqueur prédictif de la réponse thérapeutique

Run-In Phase III Trial Design With Pharmacodynamics Predictive Biomarkers

Hong, Fangxin ; Simon, Richard

Background Developments in biotechnology have stimulated the use of predictive biomarkers to identify patients who are likely to benefit from a targeted therapy. Several randomized phase III designs have been introduced for development of a targeted therapy using a diagnostic test. Most such designs require biomarkers measured before treatment. In many cases, it has been very difficult to identify such biomarkers. Promising candidate biomarkers can sometimes be effectively measured after a [...]

Signé par une centaine d'experts internationaux, cet article présente dix axes majeurs de recherche fondamentale et translationnelle dans les domaines de la prévention et du traitement des cancers du sein

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

Eccles, Suzanne ; Aboagye, Eric ; Ali, Simak ; Anderson, Annie ; Armes, Jo ; Berditchevski, Fedor ; Blaydes, Jeremy ; Brennan, Keith ; Brown, Nicola ; Bryant, Helen ; Bundred, Nigel ; Burchell, Joy ; Campbell, Anna ; Carroll, Jason ; Clarke, Robert ; Coles, Charlotte ; Cook, Gary ; Cox, Angela ; Curtin, Nicola ; Dekker, Lodewijk ; dos Santos Silva, Isabel ; Duffy, Stephen ; Easton, Douglas ; Eccles, Diana ; Edwards, Dylan ; Edwards, Joanne ; Evans, D ; Fenlon, Deborah ; Flanagan, James ; Foster, Claire

INTRODUCTION:Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS:More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; [...]