Cet article fait le point sur les études récentes concernant le traitement des cancers par la photothérapie dynamique combinée à des inhibiteurs de l'angiogenèse

Angiogenesis inhibition for the improvement of photodynamic therapy: The revival of a promising idea

Weiss, Andrea ; den Bergh, Hubert van ; Griffioen, Arjan W. ; Nowak-Sliwinska, Patrycja

Photodynamic therapy (PDT) is a minimally invasive form of treatment, which is clinically approved for the treatment of angiogenic disorders, including certain forms of cancer and neovascular eye diseases. Although the concept of PDT has existed for a long time now, it has never made a solid entrance into the clinical management of cancer. This is likely due to secondary tissue reactions, such as inflammation and neoangiogenesis. The recent development of clinically effective angiogenesis [...]

Menée sur 33 patients atteints d'un cancer du poumon non à petites cellules récidivant, cette étude évalue, du point de vue de la survie à long terme, la toxicité et l'efficacité d'une seconde radiothérapie combinée à une hyperthermie régionale et identifie les facteurs prédictifs associés à l'évolution de la maladie

Re-irradiation plus regional hyperthermia for recurrent non-small cell lung cancer: A potential modality for inducing long-term survival in selected patients

Ohguri, Takayuki ; Imada, Hajime ; Yahara, Katsuya ; Moon, Seung Dae ; Yamaguchi, Shinsaku ; Yatera, Kazuhiro ; Mukae, Hiroshi ; Hanagiri, Takeshi ; Tanaka, Fumihiro ; Korogi, Yukunori

Purpose : The purpose of this study was to assess the toxicity and efficacy of re-irradiation plus regional hyperthermia for recurrent NSCLC and to identify the predictors of long-term survival. Methods and materials : A total of 33 patients with recurrent NSCLC treated with re-irradiation plus regional hyperthermia were retrospectively analyzed. The median total dose of initial radiotherapy and re-irradiation were 70 Gy and 50 Gy, respectively. A median of 5 hyperthermia treatments using an [...]

A partir de données cliniques portant sur 192 patients atteints d'un cancer localisé du pancréas et traités entre 1980 et 2009, cette étude monocentrique japonaise évalue, du point de vue de la survie globale et du contrôle local de la maladie, l'efficacité et la toxicité d'une radiothérapie intra-opératoire combinée ou non à une radiothérapie externe et analyse les facteurs pronostiques associés

Intraoperative Radiotherapy for Pancreatic Cancer: 30-Year Experience in a Single Institution in Japan

Jingu, Keiichi ; Tanabe, Takaya ; Nemoto, Kenji ; Ariga, Hisanori ; Umezawa, Rei ; Ogawa, Yoshihiro ; Takeda, Ken ; Koto, Masashi ; Sugawara, Toshiyuki ; Kubozono, Masaki ; Shimizu, Eiji ; Abe, Keiko ; Yamada, Shogo

To analyze retrospectively the results of intraoperative radiotherapy (IORT) with or without external beam radiotherapy (± EBRT) for localized pancreatic cancer in the past three decades and to analyze prognostic factors by multivariate analysis. Records for 322 patients with pancreatic cancer treated by IORT ± EBRT in Tohoku University Hospital between 1980 and 2009 were reviewed. One hundred ninety-two patients who had no distant organ metastases or dissemination at the time of laparotomy [...]

Menée entre 2002 et 2011 sur 73 patients atteints d'un cancer de la prostate unilatéral à risque faible ou intermédiaire (durée médiane de suivi : 3,7 ans), cette étude évalue les résultats oncologiques et fonctionnels d'une cryothérapie focale

Focal Cryotherapy for Clinically Unilateral, Low-Intermediate Risk Prostate Cancer in 73 Men with a Median Follow-Up of 3.7 Years

Duke, Bahn ; Andre Luis de Castro, Abreu ; Inderbir, S. Gill ; Andrew, J. Hung ; Paul, Silverman ; Mitchell, E. Gross ; Gary, Lieskovsky ; Osamu, Ukimura

Background : Evolution of cryotherapy for prostate cancer is likely to result in parenchyma-sparing modifications adjacent to the urethra and neurovascular bundle. Results of initial series of focal therapy to minimize cryosurgery-related morbidity without compromising oncologic control have been encouraging, but limited in short-term outcomes. Objective : To retrospectively report (1) median 3.7-yr follow-up experience of primary focal cryotherapy for clinically unilateral prostate cancer with [...]

Mené sur 35 patients atteints d'un glioblastome et ayant subi une résection chirurgicale ou une biopsie, cet essai prospectif de phase II évalue l'efficacité et la toxicité d'une radiochirurgie stéréotaxique en combinaison avec une radiothérapie standard pour traiter des tumeurs cérébrales à haut risque identifiées au moyen d'une spectroscopie par résonance magnétique

Phase II Trial of Radiosurgery to Magnetic Resonance Spectroscopy–Defined High-Risk Tumor Volumes in Patients with Glioblastoma Multiforme

Einstein, Douglas B. ; Wessels, Barry ; Bangert, Barbara ; Fu, Pingfu ; Nelson, A. Dennis ; Cohen, Mark ; Sagar, Stephen ; Lewin, Jonathan ; Sloan, Andrew ; Zheng, Yiran ; Williams, Jordonna ; Colussi, Valdir ; Vinkler, Robert ; Maciunas, Robert

To determine the efficacy of a Gamma Knife stereotactic radiosurgery (SRS) boost to areas of high risk determined by magnetic resonance spectroscopy (MRS) functional imaging in addition to standard radiotherapy for patients with glioblastoma (GBM). Thirty-five patients in this prospective Phase II trial underwent surgical resection or biopsy for a GBM followed by SRS directed toward areas of MRS-determined high biological activity within 2 cm of the postoperative enhancing surgical bed. The MRS [...]

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

Combining immunotherapy and targeted therapies in cancer treatment

Vanneman, Matthew ; Dranoff, Glenn

During the past two decades, the paradigm for cancer treatment has evolved from relatively nonspecific cytotoxic agents to selective, mechanism-based therapeutics. Cancer chemotherapies were initially identified through screens for compounds that killed rapidly dividing cells. These drugs remain the backbone of current treatment, but they are limited by a narrow therapeutic index, significant toxicities and frequently acquired resistance. More recently, an improved understanding of cancer [...]

Menée sur des cellules de tumeurs épithéliales et de leucémie, cette étude montre qu'une exposition transitoire à des inihibiteurs de méthylation de l'ADN, la décitabine et l'azacitidine, induit une réponse antitumorale, notamment l'inhibition de sous-populations de cellules souches cancéreuses

Transient Low Doses of DNA-Demethylating Agents Exert Durable Antitumor Effects on Hematological and Epithelial Tumor Cells

Tsai, Hsing-Chen ; Li, Huili ; Van Neste, Leander ; Cai, Yi ; Robert, Carine ; Rassool, Feyruz V ; Shin, James J ; Harbom, Kirsten M ; Beaty, Robert ; Pappou, Emmanouil ; Harris, James ; Yen, Ray-Whay Chiu ; Ahuja, Nita ; Brock, Malcolm V ; Stearns, Vered ; Feller-Kopman, David ; Yarmus, Lonny B ; Lin, Yi-Chun ; Welm, Alana L ; Issa, Jean-Pierre ; Minn, Il ; Matsui, William ; Jang, Yoon-Young ; Sharkis, Saul J ; Baylin, Stephen B ; Zahnow, Cynthia A

Reversal of promoter DNA hypermethylation and associated gene silencing is an attractive cancer therapy approach. The DNA methylation inhibitors decitabine and azacitidine are efficacious for hematological neoplasms at lower, less toxic, doses. Experimentally, high doses induce rapid DNA damage and cytotoxicity, which do not explain the prolonged time to response observed in patients. We show that transient exposure of cultured and primary leukemic and epithelial tumor cells to clinically [...]

Cet article passe en revue le rôle des polymérases PARP dans les mécanismes de réponse aux atteintes à l'ADN et analyse les développements actuels d'inhibiteurs de PARP pour le traitement des cancers

PARPs and the DNA damage response

Sousa, Fabricio G. ; Matuo, Renata ; Soares, Daniele Grazziotin ; Escargueil, Alexandre E. ; Henriques, João A.P. ; Larsen, Annette K. ; Saffi, Jenifer

ADP-ribosylation is an important posttranslational modification catalyzed by a variety of enzymes, including poly(ADP-ribose) polymerases (PARPs), which use NAD+ as a substrate to synthesize and transfer ADP-ribose units to acceptor proteins. The PARP family members possess a variety of structural domains, span a wide range of functions and localize to various cellular compartments. Among the molecular actions attributed to PARPs, their role in the DNA damage response (DDR) has been widely [...]

Mené sur 22 patients atteints d'un lymphome non hodgkinien CD20+ récidivant ou d'une leucémie lymphocytaire chronique, cet essai de phase I évalue la toxicité et l'activité antitumorale de l'obinutuzumab, un anticorps anti-CD20

A phase I study of obinutuzumab induction followed by two years of maintenance in patients with relapsed CD20-positive B-cell malignancies

Sehn, Laurie H. ; Assouline, Sarit E. ; Stewart, Douglas A. ; Mangel, Joy ; Gascoyne, Randy D. ; Fine, Gregg ; Frances-Lasserre, Susan ; Carlile, David J. ; Crump, Michael

This phase I study evaluated the safety, tolerability, pharmacokinetics, and anti-tumor activity of obinutuzumab (GA101), a glycoengineered type II anti-CD20 monoclonal antibody administered as induction followed by two years of maintenance. Cohorts of 3-6 patients received obinutuzumab (200-2000 mg) intravenously weekly for 4 weeks. Patients with a complete or partial response (or stable disease and clinical benefit) continued to receive obinutuzumab every 3 months for a maximum of 8 doses. [...]

Cet article passe en revue les stratégies mises en œuvre, depuis les études précliniques jusqu'aux essais chez l'humain, pour développer des traitements du cancer à base d'anticorps monoclonaux

Antibody therapy of cancer

Scott, Andrew M. ; Wolchok, Jedd D. ; Old, Lloyd J.

The use of monoclonal antibodies (mAbs) for cancer therapy has achieved considerable success in recent years. Antibody–drug conjugates are powerful new treatment options for lymphomas and solid tumours, and immunomodulatory antibodies have also recently achieved remarkable clinical success. The development of therapeutic antibodies requires a deep understanding of cancer serology, protein-engineering techniques, mechanisms of action and resistance, and the interplay between the immune system [...]

Cet article passe en revue les perpectives offertes par les connaissances relatives aux cellules dendritiques pour le développement d'immunothérapies du cancer

Cancer immunotherapy via dendritic cells

Palucka, Karolina ; Banchereau, Jacques

Cancer immunotherapy attempts to harness the power and specificity of the immune system to treat tumours. The molecular identification of human cancer-specific antigens has allowed the development of antigen-specific immunotherapy. In one approach, autologous antigen-specific T cells are expanded ex vivo and then re-infused into patients. Another approach is through vaccination; that is, the provision of an antigen together with an adjuvant to elicit therapeutic T cells in vivo. Owing to their [...]

Menée in vitro et à l'aide de xénogreffes, cette étude identifie un mécanisme de résistance à un nouveau composé appelé MLN4924, une petite molécule inhibant l'enzyme NAE

Treatment-Emergent Mutations in NAE

Milhollen, Michael A ; Thomas, Michael P ; Narayanan, Usha ; Traore, Tary ; Riceberg, Jessica ; Amidon, Benjamin S ; Bence, Neil F ; Bolen, Joseph B ; Brownell, James ; Dick, Lawrence R ; Loke, Huay-Keng ; McDonald, Alice A ; Ma, Jingya ; Manfredi, Mark G ; Sells, Todd B ; Sintchak, Mike D ; Yang, Xiaofeng ; Xu, Qing ; Koenig, Erik M ; Gavin, James M ; Smith, Peter G

MLN4924 is an investigational small-molecule inhibitor of NEDD8-activating enzyme (NAE) in clinical trials for the treatment of cancer. MLN4924 is a mechanism-based inhibitor, with enzyme inhibition occurring through the formation of a tight-binding NEDD8-MLN4924 adduct. In cell and xenograft models of cancer, we identified treatment-emergent heterozygous mutations in the adenosine triphosphate binding pocket and NEDD8-binding cleft of NAE

Menée in vitro et à l'aide de xénogreffes, cette étude suggère qu'un anticorps monoclonal ciblé sur l'éphrine B2 pourrait, seul ou en combinaison, être efficace contre l'angiogenèse

Blocking ephrin-B2 with highly specific antibodies inhibits angiogenesis, lymphangiogenesis, and tumor growth

Abéngozar, María Angeles ; de Frutos, Sergio ; Ferreiro, Sergio ; Soriano, Joaquím ; Perez-Martinez, Manuel ; Olmeda, David ; Marenchino, Marco ; Cañamero, Marta ; Ortega, Sagrario ; Megías, Diego ; Rodriguez, Antonio ; Martínez-Torrecuadrada, Jorge L.

Membrane-anchored ephrinB2 and its receptor EphB4 are involved in the formation of blood and lymphatic vessels in normal and pathological conditions. Eph/ephrin activation requires cell-cell interactions and leads to bidirectional signaling pathways in both ligand- and receptor-expressing cells. To investigate the functional consequences of blocking ephrinB2 activity, two highly specific human single-chain Fv (scFv) antibody fragments against ephrinB2 were generated and characterized. Both [...]

Cette étude met en évidence un mécanisme permettant de rendre compte du faible intérêt d'un traitement à l'interleukine 12 chez les patients atteints d'un lymphome folliculaire

IL-12 upregulates TIM-3 expression and induces T cell exhaustion in patients with follicular B cell non-Hodgkin lymphoma

Yang, Zhi-Zhang ; Grote, Deanna M. ; Ziesmer, Steven C. ; Niki, Toshiro ; Hirashima, Mitsuomi ; Novak, Anne J. ; Witzig, Thomas E. ; Ansell, Stephen M.

The cytokine IL-12 induces IFN-γ production by T and NK cells. In preclinical models, it contributes to antitumor immunity. However, in clinical testing, it has shown limited benefit in patients with any one of a variety of malignancies. Moreover, in a clinical trial testing a combination of IL-12 and rituximab in patients with follicular B cell non-Hodgkin lymphoma (FL), those treated with IL-12 showed a lower response rate, suggesting that IL-12 actually plays a detrimental role. Here, we [...]

Cet article passe en revue les défis posés par le ciblage des cellules souches cancéreuses pour le traitement des cancers du poumon

Can lung cancer stem cells be targeted for therapies?

Wu, Xiaodan ; Chen, Hong ; Wang, Xiangdong

Lung cancer is the leading cause of cancer death, with a poor prognosis. Lung cancer stem cells (CSCs) are proposed as one of therapeutic targets for lung cancer. It is important to understand the exact role of lung CSC subpopulations in tumor initiation, recurrence, drug resistance and metastasis and explore biomarkers, signaling pathways and differentiation regulation specific to lung CSCs. Numerous measures targeting lung CSCs, e.g. genomics, proteomics and bioinformatics, have been used to [...]

Menée sur des lignées cellulaires de cancer du poumon non à petites cellules, cette étude évalue l'efficacité d'une stratégie thérapeutique combinant un petit ARN interférent spécifique du récepteur EGFR et un inhibiteur de tyrosine kinase, tel que l'afatinib, ou le cetuximab

Targeting the epidermal growth factor receptor in non-small cell lung cancer cells: the effect of combining RNA interference with tyrosine kinase inhibitors or cetuximab

Chen, Gang ; Kronenberger, Peter ; Teugels, Erik ; Adaku Umelo, Ijeoma ; De Greve, Jacques

BACKGROUND:The epidermal growth factor receptor (EGFR) is a validated therapeutic target in non-small cell lung cancer (NSCLC). However, current single agent receptor targeting does not achieve a maximal therapeutic effect, and some mutations are resistant to current available agents. In the current study we have examined, in different NSCLC cell lines, the combined effect of RNA interference targeting the EGFR mRNA, and inactivation of EGFR signaling using different receptor tyrosine kinase [...]

Mené sur 192 patients atteints d'un carcinome à cellules claires du rein, cet essai de phase II évalue, du point de vue de la durée avant progression tumorale, deux modes d'administration du sunitinib

Randomized Phase II Trial of Sunitinib on an Intermittent Versus Continuous Dosing Schedule As First-Line Therapy for Advanced Renal Cell Carcinoma

Motzer, Robert J. ; Hutson, Thomas E. ; Olsen, Mark R. ; Hudes, Gary R. ; Burke, John M. ; Edenfield, William J. ; Wilding, George ; Agarwal, Neeraj ; Thompson, John A. ; Cella, David ; Bello, Akintunde ; Korytowsky, Beata ; Yuan, Jinyu ; Valota, Olga ; Martell, Bridget ; Hariharan, Subramanian ; Figlin, Robert A.

Purpose Sunitinib has shown antitumor activity with a manageable safety profile as metastatic renal cell carcinoma (RCC) treatment, when given by the standard intermittent schedule as well as a continuous daily dosing (CDD) schedule. A trial was conducted to compare the schedules.Patients and Methods Patients with treatment-naive, clear cell advanced RCC were randomly assigned 1:1 to receive sunitinib 50 mg/d for 4 weeks followed by 2 weeks off treatment (schedule 4/2; n = 146) or 37.5 mg/d on [...]

Mené sur 17 patients atteints d'un sarcome de Kaposi lié à une infection par le VIH, cet essai de phase II évalue la toxicité et l'activité antitumorale du bevacizumab

Phase II Study of Bevacizumab in Patients With HIV-Associated Kaposi's Sarcoma Receiving Antiretroviral Therapy

Uldrick, Thomas S. ; Wyvill, Kathleen M. ; Kumar, Pallavi ; O'Mahony, Deirdre ; Bernstein, Wendy ; Aleman, Karen ; Polizzotto, Mark N. ; Steinberg, Seth M. ; Pittaluga, Stefania ; Marshall, Vickie ; Whitby, Denise ; Little, Richard F. ; Yarchoan, Robert

Purpose Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti–VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS.Patients and Methods Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months [...]

Menée sur 129 patientes atteintes d'un cancer métastatique du sein, cette étude évalue, du point de vue du taux de réponse objective, l'ajout de doxorubicine liposomale pégylée au carboplatine, avec ou sans trastuzumab

Pegylated liposomal doxorubicin plus carboplatin in patients with metastatic breast cancer: a phase II study

Collea, R. P. ; Kruter, F. W. ; Cantrell, J. E. ; George, T. K. ; Kruger, S. ; Favret, A. M. ; Lindquist, D. L. ; Melnyk, A. M. ; Pluenneke, R. E. ; Shao, S. H. ; Crockett, M. W. ; Asmar, L. ; O’Shaughnessy, J.

Background: We determined the objective response rates produced by pegylated liposomal doxorubicin (PLD) plus carboplatin with/without trastuzumab (Herceptin).Patients and methods: Patients with measurable disease were stratified by taxane treatment history and human epidermal growth factor receptor-2 status. Treatment: PLD 30 mg/m2 followed by carboplatin, day 1 of each 28-day cycle; human epidermal growth factor receptor-2 (HER2)-positive patients also received trastuzumab.Results: Arm 1 [...]

Menée in vitro et à l'aide de xénogreffes, cette étude évalue l'intérêt de la liquiritigénine, un agoniste du récepteur β des estrogènes, pour le traitement de patients atteints d'un gliome

Therapeutic significance of estrogen receptor β agonists in gliomas

Sareddy, Gangadhara Reddy ; Nair, Binoj C ; Gonugunta, Vijaya K ; Zhang, Quan-guang ; Brenner, Andrew J ; Brann, Darrell W ; Tekmal, Rajeshwar Rao ; Vadlamudi, Ratna K.

Gliomas are the most common and devastating central nervous system neoplasms. A gender bias exists in their development: females are at lower risk than males, implicating estrogen-mediated protective effects. Estrogen functions are mediated by two ER subtypes: ERβ, that functions as tumor promoter and ERβ that function as tumor suppressor. We examined the potential use of ERβ agonists as a novel therapeutic to curb the growth of gliomas. Western analysis of six glioma model cells showed [...]

A partir de données portant sur des patients atteints d'un carcinome métastatique à cellules rénales et inclus dans l'essai de phase III RECORD-1, cette étude analyse de façon rétrospective la toxicité et l'efficacité de l'évérolimus chez les patients qui avaient préalablement interrompu un traitement par inhibiteurs de tyrosine kinase de VEGFR pour cause de toxicité

Everolimus in metastatic renal cell carcinoma patients intolerant to previous VEGFr-TKI therapy: a RECORD-1 subgroup analysis

Bracarda, S. ; Hutson, T. E. ; Porta, C. ; Figlin, R. A. ; Calvo, E. ; Grunwald, V. ; Ravaud, A. ; Motzer, R. ; Kim, D. ; Anak, O. ; Panneerselvam, A. ; Escudier, B.

Background: A relevant percentage of patients with metastatic renal cell carcinoma develop intolerance to vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFr-TKIs) and require careful selection of subsequent treatment. This retrospective analysis evaluated the safety and efficacy of everolimus in patients enrolled in the phase-III RECORD-1 trial who discontinued previous VEGFr-TKI therapy because of toxicity. Methods: Patients with an adverse event (AE) as their [...]

Cet article passe en revue les travaux récents sur le traitement et la prise en charge des cancers métastatiques du sein

Current approaches to the management of Her2-negative metastatic breast cancer

Gogineni, Keerthi ; DeMichele, Angela

While metastatic breast cancer (MBC) remains incurable, a vast array of active therapeutic agents has provided the opportunity for long-term disease control while maintaining quality of life and physical function. Optimal management of MBC balances a multitude of factors, including a woman's performance status, social support, symptoms, disease burden, prior therapies, and surrogates for tumor biology. Choosing the most appropriate initial therapy and subsequent sequence of treatments demands [...]

Cet article passe en revue les travaux récents sur le traitement des tumeurs germinales du testicule

The Contemporary Role of Chemotherapy for Advanced Testis Cancer: A Systematic Review of the Literature

Fabio, Calabrò ; Peter, Albers ; Carsten, Bokemeyer ; Chris, Martin ; Lawrence, H. Einhorn ; Alan, Horwich ; Susanne, Krege ; Hans Joachim, Schmoll ; Cora, N. Sternberg ; Gedske, Daugaard

Context: Germ cell tumours (GCTs) of the testis are the most common cancer in young men; they are also one of the most curable cancers. Standard treatment of metastatic GCTs has evolved on the basis of randomised trials and prognostic factors. Objective: This review summarises the evolving role of chemotherapy in the treatment of previously treated and untreated patients with metastatic GCTs and outlines the current standard treatment. Evidence acquisition: Randomised and nonrandomised trials [...]

Mené sur 52 patients atteints d'un lymphome hodgkinien de stade précoce et présentant une atteinte médiastinale, cette étude évalue les résultats dosimétriques et cliniques d'une radiothérapie avec modulation d'intensité consécutive à une chimiothérapie

Dosimetric and Clinical Outcomes of Involved-Field Intensity-Modulated Radiotherapy After Chemotherapy for Early-Stage Hodgkin’s Lymphoma with Mediastinal Involvement

Lu, Ning-Ning ; Li, Ye-Xiong ; Wu, Run-Ye ; Zhang, Xi-Mei ; Wang, Wei-Hu ; Jin, Jing ; Song, Yong-Wen ; Fang, Hui ; Ren, Hua ; Wang, Shu-Lian ; Liu, Yue-Ping ; Liu, Xin-Fan ; Chen, Bo ; Dai, Jian-Rong ; Yu, Zi-Hao

To evaluate the dosimetric and clinical outcomes of involved-field intensity-modulated radiotherapy (IF-IMRT) for patients with early-stage Hodgkin’s lymphoma (HL) with mediastinal involvement. Fifty-two patients with early-stage HL that involved the mediastinum were reviewed. Eight patients had Stage I disease, and 44 patients had Stage II disease. Twenty-three patients (44%) presented with a bulky mediastinum, whereas 42 patients (81%) had involvement of both the mediastinum and either [...]

Mené sur 119 patients atteints d'un cancer colorectal avec métastases hépatiques non résécables, cet essai randomisé de phase II évalue, du point de vue de la survie sans progression et de la survie globale à 30 mois, l'intérêt de combiner un traitement systémique à une ablation de métastases par radiofréquences

Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004)

Ruers, T. ; Punt, C. ; Van Coevorden, F. ; Pierie, J. P. E. N. ; Borel-Rinkes, I. ; Ledermann, J. A. ; Poston, G. ; Bechstein, W. ; Lentz, M. A. ; Mauer, M. ; Van Cutsem, E. ; Lutz, M. P. ; Nordlinger, B.

Background: This study investigates the possible benefits of radiofrequency ablation (RFA) in patients with non-resectable colorectal liver metastases.Methods: This phase II study, originally started as a phase III design, randomly assigned 119 patients with non-resectable colorectal liver metastases between systemic treatment (n = 59) or systemic treatment plus RFA (±resection) (n = 60). Primary objective was a 30-month overall survival (OS) rate >38% for the combined treatment group.Results: [...]

Cet article fait le point sur les études récentes concernant les différentes stratégies de préservation du larynx dans le traitement d'un cancer de cet organe

Larynx preservation

Lefebvre, Jean-Louis

Purpose of review: Organ preservation, in particular larynx preservation, is a major challenge that has been evaluated during the past 3 decades. This review took in consideration the most recently published articles on this topic. Recent findings: There are no new data on this topic but mainly confirming data. Most of the reports underscored that there was still a place for upfront surgery (either partial or total laryngectomy). Nonsurgical approaches are radiotherapy alone or [...]

Cet article présente une nouvelle approche faisant appel à la biologie des systèmes et à la pharmacodynamique pour faciliter le développement de traitements personnalisés

Merging Systems Biology with Pharmacodynamics

Iyengar, Ravi ; Zhao, Shan ; Chung, Seung-Wook ; Mager, Donald E. ; Gallo, James M.

The emerging discipline of systems pharmacology aims to combine analysis and computational modeling of cellular regulatory networks with quantitative pharmacology approaches to drive the drug discovery processes, predict rare adverse events, and catalyze the practice of personalized precision medicine. Here, we introduce the concept of enhanced pharmacodynamic (ePD) models, which synergistically combine the desirable features of systems biology and current PD models within the framework of [...]

Menée par entretiens auprès de 26 patients britanniques invités à participer à un essai clinique, cette étude évalue leur degré de compréhension du document d'information qui leur est remis

Do informed consent documents for cancer trials do what they should? A study of manifest and latent functions

Armstrong, Natalie ; Dixon-Woods, Mary ; Thomas, Anne ; Rusk, Gill ; Tarrant, Carolyn

Though patient information leaflets (PILs) are provided to those invited to take part in medical research, they usually fall short in facilitating informed decisions about participation. We aimed to explore why there is an enduring requirement for a process that seems not to ‘work’, and to explain why the problems have proven resistant to correction. We analysed applications for ethical approval for 13 oncology trials and related official guidance. We interviewed 26 patients invited to [...]

Cet article passe en revue les essais cliniques qui ont servi de base à l'autorité réglementaire américaine pour autoriser la mise sur le marche de traitements du cancer du sein métastatique au cours des deux dernières décennies

US Food and Drug Administration Approval Overview in Metastatic Breast Cancer

Cortazar, Patricia ; Justice, Robert ; Johnson, John ; Sridhara, Rajeshwari ; Keegan, Patricia ; Pazdur, Richard

We reviewed trials that supported US Food and Drug Administration (FDA) approvals of drugs and biologics for the treatment of metastatic breast cancer (MBC) in the last two decades. This summary provides an overview of the basis for approval, including end points, trial design, major trial findings, and regulatory considerations. Approval of hormonal agents is excluded from this analysis. In the last two decades, 10 products with 14 MBC indications (four for first-line and 10 for second- to [...]