Traitements

Cet article passe en revue les études récentes concernant l'utilisation de l'électrochimiothérapie dans le traitement d'un mélanome de stade avancé

• Utility of electrochemotherapy in melanoma treatment
  • Current Opinion in Oncology, sous presse, 2012 (résumé)
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  Cet article passe en revue les études récentes concernant l'utilisation de l'électrochimiothérapie dans le traitement d'un mélanome de stade avancé

  “Utility of electrochemotherapy in melanoma treatment”

  • Testori, Alessandro;Rossi, Carlo R.;Tosti, Giulio

  Purpose of review: In the present study, the role of electrochemotherapy (ECT) in the advanced melanoma setting, either as alternative treatment modality to conventional therapies or as palliative care, is reviewed and the perspective to combine ECT with biological response modifiers and immunotherapeutic compounds is discussed. Recent findings: ECT refers to the combination of electroporation and administration of anticancer drugs for local treatment of solid neoplasms. Electroporation uses short and intense electric pulses to induce a transient permeabilization of the cell membrane by creation of pores, thus allowing molecules, such as chemotherapeutic agents, to freely diffuse into the cytosol. ECT has shown to be effective and clinically well tolerated in the local control of primary and metastatic solid tumors of diverse histotypes in preclinical and clinical studies, thus, emerging as useful local treatment modality for disseminated superficial melanoma. So far, only a few data ...

  
  

Mots clés : Mélanome; Traitements (Traitements localisés : découverte et développement)

Mené sur 148 patients atteints d'un cancer non invasif de la vessie, cet essai prospectif randomisé évalue l'effet d'une résection transurétrale de la vessie, combinée à une cystoscopie à bande spectrale étroite, sur le risque de récidive à un an

• A Randomized Prospective Trial to Assess the Impact of Transurethral Resection in Narrow Band Imaging Modality on NonMuscle-Invasive Bladder Cancer Recurrence
  • European urology, sous presse, 2012 (résumé)
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  Mené sur 148 patients atteints d'un cancer non invasif de la vessie, cet essai prospectif randomisé évalue l'effet d'une résection transurétrale de la vessie, combinée à une cystoscopie à bande spectrale étroite, sur le risque de récidive à un an

  “A Randomized Prospective Trial to Assess the Impact of Transurethral Resection in Narrow Band Imaging Modality on NonMuscle-Invasive Bladder Cancer Recurrence”

  • Angelo, Naselli;Carlo, Introini;Luca, Timossi;Bruno, Spina;Vincenzo, Fontana;Riccardo, Pezzi;Francesco, Germinale;Franco, Bertolotto;Paolo, Puppo

  Background : Narrow band imaging (NBI) is an optical enhancement technology that filters white light into two bandwidths of illumination centered on 415 nm (blue) and 540 nm (green). NBI cystoscopy can increase bladder cancer (BCa) visualization and detection at the time of transurethral resection (TUR). NBI may therefore reduce subsequent relapse following TUR. Objective : Assess the impact of NBI modality on 1-yr non–muscle-invasive BCa (NMIBC) recurrence risk. Design, setting, and participants : Consecutive patients with overt or suspected BCa were included in a prospective study powered to test a 10% difference in 1-yr recurrence risk in favor of cases submitted to NBI TUR. Excluding patients with muscle-invasive BCa, negative pathologic examination, or without follow-up, the study population was composed of 148 subjects randomized from August 2009 to September 2010 to NBI TUR (76 cases) or white light (WL) TUR (72 cases). Intervention : TUR was performed in NBI or standard WL ...

  
  

Mots clés : Vessie; Traitements (Traitements localisés : applications cliniques)

Menée auprès de 1 440 patientes atteintes d'un cancer du sein de stade précoce, cette étude analyse les facteurs associés à une récidive homolatérale du cancer, après une thérapie conservatrice du sein par irradiation partielle accélérée (durée de suivi : 5 ans)

• Outcome after ipsilateral breast tumor recurrence in patients who receive accelerated partial breast irradiation
  • Cancer, sous presse, 2012 (résumé)
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  Menée auprès de 1 440 patientes atteintes d'un cancer du sein de stade précoce, cette étude analyse les facteurs associés à une récidive homolatérale du cancer, après une thérapie conservatrice du sein par irradiation partielle accélérée (durée de suivi : 5 ans)

  “Outcome after ipsilateral breast tumor recurrence in patients who receive accelerated partial breast irradiation”

  • Shah, Chirag;Vicini, Frank;Keisch, Martin;Kuerer, Henry;Beitsch, Peter;Haffty, Bruce;Lyden, Maureen

  BACKGROUND: The objective of this study was to examine clinical outcomes and patterns of failure in patients with early stage breast cancer who developed an ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) using accelerated partial breast irradiation (APBI). METHODS: In total, 1440 patients (1449 tumors) with early stage breast cancer who underwent BCT were treated with the MammoSite device to deliver APBI (34 Gray [Gy] in 3.4-Gy fractions). One thousand two hundred fifty-five patients (87%) had invasive breast cancer (IBC) (median tumor size, 10 mm), and 194 patients (13%) had ductal carcinoma in situ (DCIS) (median tumor size, 8 mm). The median follow-up was 60 months. RESULTS: Fifty patients (3.5%) developed an IBTR for a 5-year actuarial rate of 3.61% (3.65% for IBC and 3.36% for DCIS). It was determined that 36 recurrences (72%) represented new primary cancers, and 14 recurrences (28%) represented recurrences of the index lesion. Of the 32 ...

  
  

Mots clés : Sein; Traitements (Traitements localisés : applications cliniques)

A partir d'une revue systématique de la littérature publiée entre 1980 et 2011 (40 études), cette étude évalue, en fonction des techniques chirurgicales utilisées, les résultats fonctionnels d'une prostatectomie radicale de sauvetage pour traiter un cancer de la prostate récidivant après une radiothérapie et analyse l'impact de la résection sur l'évolution de la maladie

• Cancer Control and Functional Outcomes of Salvage Radical Prostatectomy for Radiation-recurrent Prostate Cancer: A Systematic Review of the Literature
  • European urology, sous presse, 2012 (résumé)
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  A partir d'une revue systématique de la littérature publiée entre 1980 et 2011 (40 études), cette étude évalue, en fonction des techniques chirurgicales utilisées, les résultats fonctionnels d'une prostatectomie radicale de sauvetage pour traiter un cancer de la prostate récidivant après une radiothérapie et analyse l'impact de la résection sur l'évolution de la maladie

  “Cancer Control and Functional Outcomes of Salvage Radical Prostatectomy for Radiation-recurrent Prostate Cancer: A Systematic Review of the Literature”

  • Daher, C. Chade;James, Eastham;Markus, Graefen;Jim, C. Hu;R. Jeffrey Karnes;Laurence, Klotz;Francesco, Montorsi;Hendrik van, Poppel;Peter, T. Scardino;Shahrokh, F. Shariat

  Context : Prostate cancer (PCa) recurrence following definitive radiation therapy (RT) remains a vexing challenge for the practicing physician. Salvage radical prostatectomy (SRP) has not been recognized yet as a valuable therapeutic option. Objective : We critically analyzed the currently available evidence on SRP as to patient selection, predictive oncologic factors, surgical technique, cancer control, surgical complications, functional outcomes, and comparison to other salvage therapies. Evidence acquisition : A systematic review of the literature was performed in June 2011 using the Medline, Embase, and Web of Science databases, limiting the review to English-language articles published between January 1980 and June 2011. All authors reviewed the list of references and added papers relevant to the topic of the review prior to the analysis. The panel selected 40 articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Evidence ...

  
  

Mots clés : Prostate; Traitements (Traitements localisés : applications cliniques)

Menée sur 77 patients présentant des métastases pulmonaires, cette étude prospective observationnelle évalue les effets d'une métastasectomie par résection cunéiforme sur la fonction pulmonaire

• Changes in lung function parameters after wedge resections: A prospective evaluation of metastasectomy patients
  • Chest, sous presse, 2012 (résumé)
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  Menée sur 77 patients présentant des métastases pulmonaires, cette étude prospective observationnelle évalue les effets d'une métastasectomie par résection cunéiforme sur la fonction pulmonaire

  “Changes in lung function parameters after wedge resections: A prospective evaluation of metastasectomy patients”

  • Welter, Stefan;Cheufou, Danjouma;Sommerwerck, Urte;Maletzki, Frank;Stamatis, Georgios

  Background: Pulmonary metastasectomy with lung sparing local excisions is a widely accepted method to treat stage IV malignancies in selected cases. The ability to predict postoperative lung function is an unresolved issue, especially when multiple wedge resections are planned. To help develop a method to predict postoperative lung function after wedge resections, we present this prospective observational study. Methods : A total of 77 patients who underwent one or more wedge resections to remove lung metastases completed the study protocol. Spirometry results, diffusion capacity for carbon monoxide (DLCO) and blood gases and potential confounding factors were measured prior to, immediately following and three months after the procedure and were analyzed.Results: Seventy-seven patients with a median age of 61.3 years underwent one up to 22 wedge resections. The mean lung function losses were FVC (-7.5 %), TLC (-7.9 %), FEV1 (-9.2 %) and DLCO (-8.8 %) and all were statistically ...

  
  

Mots clés : Poumon; Traitements (Traitements localisés : applications cliniques)

Menée entre1998 et 2010 sur 483 patients atteints d'un cancer du poumon non à petites cellules de stade précoce et présentant une fonction pulmonaire déficiente, cette étude multicentrique évalue la toxicité et l'efficacité d'une radiothérapie stéréotaxique corporelle guidée par l'image

• Is There a Lower Limit of Pretreatment Pulmonary Function for Safe and Effective Stereotactic Body Radiotherapy for Early-Stage Non-small Cell Lung Cancer?
  • Journal of Thoracic Oncology, sous presse, 2012 (résumé)
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  Menée entre1998 et 2010 sur 483 patients atteints d'un cancer du poumon non à petites cellules de stade précoce et présentant une fonction pulmonaire déficiente, cette étude multicentrique évalue la toxicité et l'efficacité d'une radiothérapie stéréotaxique corporelle guidée par l'image

  “Is There a Lower Limit of Pretreatment Pulmonary Function for Safe and Effective Stereotactic Body Radiotherapy for Early-Stage Non-small Cell Lung Cancer?”

  • Guckenberger, Matthias;Kestin, Larry L.;Hope, Andrew J.;Belderbos, Jose;Werner-Wasik, Maria;Yan, Di;Sonke, Jan-Jakob;Bissonnette, Jean Pierre;Wilbert, Juergen;Xiao, Ying;Grills, Inga S.

  Introduction: To evaluate the influence of pretreatment pulmonary function (PF) on survival, early and late pulmonary toxicity after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer. Methods: Four hundred eighty-three patients with 505 tumors of early-stage non-small cell lung cancer cT1-3 cN0 were treated with image-guided SBRT at five international institutions (1998-2010). Sixty-four percent of the tumors were biopsy-proven and 18F-fluorodeoxyglucose-positron emission tomography was performed for staging in 84%. Image-guided SBRT was performed with a median of three fractions to a median total dose of 54 Gy. Pretreatment PF was available for 423 patients, and 617 posttreatment PF tests from 270 patients were available. Results: A large variability of pretreatment PF was observed: the 90% range of forced expiratory volume in 1 second and diffusing capacity for carbon monoxide was 29 to 109% and 5.5 to 19.1 ml/min/mmHg, respectively. PF was ...

  
  

Mots clés : Poumon; Traitements (Traitements localisés : applications cliniques)

Mené sur 384 patients atteints d'un cancer localement avancé du rectum, cette étude suisse évalue l'effet d'une radiothérapie préopératoire sur la survie des patients

• Impact of preoperative radiotherapy on survival in locally advanced rectal cancer: an observational population-based study from the South of Switzerland
  • European Journal of Cancer Prevention, Vol. 21 (2), 2012 (résumé)
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  Mené sur 384 patients atteints d'un cancer localement avancé du rectum, cette étude suisse évalue l'effet d'une radiothérapie préopératoire sur la survie des patients

  “Impact of preoperative radiotherapy on survival in locally advanced rectal cancer: an observational population-based study from the South of Switzerland”

  • Spitale, Alessandra;Franzetti-Pellanda, Alessandra;Mazzola, Paola;Richetti, Antonella;Mazzuchelli, Luca;Bordoni, Andrea

  Preoperative radiotherapy (RT) followed by surgery is widely accepted in the treatment of locally advanced rectal cancer (LARC). This study aimed to estimate at the population-based level the impact of preoperative RT on overall survival (OS) and cancer-specific survival (CSS) in LARCs diagnosed in Southern Switzerland between 1996 and 2007. All patients with LARC were selected from the Ticino Cancer Registry database. Patients were categorized according to the first administered treatment: preoperative radiotherapy (RT) followed by surgery (RT+) versus surgery (RT−). Clinical–pathological characteristics and 5-year OS and CSS were analysed. Among 384 patients with LARC, 54% underwent preoperative RT, occurring more frequently in the mid-distal part of the rectum compared with the RT− group (74.8 vs. 29.8%, respectively). Both 5-year OS and CSS significantly improved in RT+ patients (OS: 68 vs. 54%, respectively; CSS: 71 vs. 63%, respectively). The adjusted hazard ratio for all ...

  
  

Mots clés : Colon-rectum; Traitements (Traitements localisés : applications cliniques)

Menée sur un échantillon tumoral prélevé sur un patient atteint d'un cancer de la prostate, cette étude de séquençage identifie la présence d'une mutation du gène d'une enzyme, la méthylthioadénine phosphorylase, et, à l'aide d'une xénogreffe, suggère l'efficacité d'un traitement à l'aide de méthylthioadénosine

• Next Generation Sequencing of Prostate Cancer from a Patient Identifies a Deficiency of Methylthioadenine Phosphorylase (MTAP), an Exploitable Tumor Target
  • Molecular Cancer Therapeutics, sous presse, 2012 (résumé)
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  Menée sur un échantillon tumoral prélevé sur un patient atteint d'un cancer de la prostate, cette étude de séquençage identifie la présence d'une mutation du gène d'une enzyme, la méthylthioadénine phosphorylase, et, à l'aide d'une xénogreffe, suggère l'efficacité d'un traitement à l'aide de méthylthioadénosine

  “Next Generation Sequencing of Prostate Cancer from a Patient Identifies a Deficiency of Methylthioadenine Phosphorylase (MTAP), an Exploitable Tumor Target”

  • Collins, Colin C;Volik, Stanislav V;Lapuk, Anna;Wang, Yuwei;Gout, Peter W;Wu, Chunxiao;Xue, Hui;Cheng, Hongwei;Haegert, Anne;Bell, Robert H;Brahmbhatt, Sonal;Anderson, Shawn;Fazli, Ladan;Hurtado-Coll, Antonio;Rubin, Mark A;Demichelis, Francesca;Beltran, Himisha;Hirst, Martin;Marra, Marco A;Maher, Christopher A;Chinnaiyan, Arul M;Gleave, Martin E;Bertino, Joseph R;Lubin, Martin;Wang, Yuzhuo

  Castrate resistant prostate cancer (CRPC) and neuroendocrine carcinoma of the prostate are invariably fatal diseases for which only palliative therapies exist. As part of a prostate tumour sequencing program, a patient tumour was analyzed using Illumina genome sequencing and a matched renal capsule tumour xenograft was generated. Both tumour and xenograft had a homozygous 9p21 deletion spanning the MTAP, CDKN2 and ARF genes. It is rare for this deletion to occur in primary prostate tumours yet approximately 10% express decreased levels of MTAP mRNA. Decreased MTAP expression is a prognosticator for poor outcome. Moreover, it appears that this deletion is more common in CRPC than in primary prostate cancer. We show for the first time that treatment with methylthioadenosine and high dose 6-thioguanine causes marked inhibition of a patient derived neuroendocrine xenograft growth while protecting the host from 6- thioguanine toxicity. This therapeutic approach can be applied to other ...

  
  

Mots clés : Prostate; Traitements (Traitements systémiques : découverte et développement)

Menée à l'aide de xénogreffes de tumeurs humaines de la prostate, cette étude évalue l'activité antitumorale d'un composé appelé ARN-509, un inhibiteur du récepteur aux androgènes

• ARN-509: a novel anti-androgen for prostate cancer treatment
  • Cancer Research, sous presse, 2012 (résumé)
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  Menée à l'aide de xénogreffes de tumeurs humaines de la prostate, cette étude évalue l'activité antitumorale d'un composé appelé ARN-509, un inhibiteur du récepteur aux androgènes

  “ARN-509: a novel anti-androgen for prostate cancer treatment”

  • Clegg, Nicola J;Wongvipat, John;Tran, Chris;Ouk, Samedy;Dilhas, Anna;Joseph, Jim;Chen, Yu;Grillot, Kate;Bischoff, Eric D;Cai, Ling;Aparicio, Anna;Dorow, Steven;Arora, Vivek;Shao, Gang;Qian, Jing;Zhao, Hong;Yang, Guangbin;Cao, Chunyan;Sensintaffar, John;Wasielewska, Teresa;Herbert, Mark R;Bonnefous, Celine;Darimont, Beatrice;Scher, Howard I.;Smith-Jones, Peter M;Klang, Mark;Smith, Nicholas D;de Stanchina, Elisa;Wu, Nian;Ouerfelli, Ouathek;Rix, Peter;Heyman, Richard;Jung, Michael E;Sawyers, Charles L.;Hager, Jeffrey H

  Continued reliance on the androgen receptor (AR) is now understood as a core mechanism in castration-resistant prostate cancer (CRPC), the most advanced form of this disease. While established and novel AR-pathway targeting agents display clinical efficacy in metastatic CRPC, dose-limiting side effects remain problematic for all current agents. In this study, we report the discovery and development of ARN-509, a competitive AR inhibitor this is fully antagonistic to AR overexpression, a common and important feature of CRPC. ARN-509 was optimized for inhibition of AR transcriptional activity and prostate cancer cell proliferation, pharmacokinetics and in vivo efficacy. In contrast to bicalutamide, ARN-509 lacked significant agonist activity in preclinical models of CRPC. Moreover, ARN-509 lacked inducing activity for AR nuclear localization or DNA binding. In a clinically valid murine xenograft model of human CRPC, ARN-509 showed greater efficacy than MDV3100. Maximal therapeutic ...

  
  

Mots clés : Prostate; Traitements (Traitements systémiques : découverte et développement)

Menée sur des patients atteints d'un cancer du poumon non à petites cellules, cette étude évalue, à l'aide d'imagerie par tomographie par émission de positrons, l'effet du bevacizumab sur la capacité du docétaxel à pénétrer à l'intérieur des tumeurs

• Rapid Decrease in Delivery of Chemotherapy to Tumors after Anti-VEGF Therapy: Implications for Scheduling of Anti-Angiogenic Drugs
  • Cancer cell, Vol. 21 (1), pp. 82-91, 2012 (résumé)
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  Menée sur des patients atteints d'un cancer du poumon non à petites cellules, cette étude évalue, à l'aide d'imagerie par tomographie par émission de positrons, l'effet du bevacizumab sur la capacité du docétaxel à pénétrer à l'intérieur des tumeurs

  “Rapid Decrease in Delivery of Chemotherapy to Tumors after Anti-VEGF Therapy: Implications for Scheduling of Anti-Angiogenic Drugs”

  • Van der Veldt, Astrid A M.;Lubberink, Mark;Bahce, Idris;Walraven, Maudy;de Boer, Michiel P;Greuter, Henri N J. M.;Hendrikse, N.  Harry;Eriksson, Jonas;Windhorst, Albert D;Postmus, Pieter E;Verheul, Henk M;Serné, Erik H;Lammertsma, Adriaan A;Smit, Egbert F

  Current strategies combining anti-angiogenic drugs with chemotherapy provide clinical benefit in cancer patients. It is assumed that anti-angiogenic drugs, such as bevacizumab, transiently normalize abnormal tumor vasculature and contribute to improved delivery of subsequent chemotherapy. To investigate this concept, a study was performed in non-small cell lung cancer (NSCLC) patients using positron emission tomography (PET) and radiolabeled docetaxel ([11C]docetaxel). In NSCLC, bevacizumab reduced both perfusion and net influx rate of [11C]docetaxel within 5 hr. These effects persisted after 4 days. The clinical relevance of these findings is notable, as there was no evidence for a substantial improvement in drug delivery to tumors. These findings highlight the importance of drug scheduling and advocate further studies to optimize scheduling of anti-angiogenic drugs. º Drug delivery to tumors can be measured using PET and radiolabeled drugs º The anti-angiogenic drug bevacizumab ...

  
  

Mots clés : Poumon; Traitements (Traitements systémiques : découverte et développement)

Menée sur 21 échantillons tumoraux prélevés sur des patients traités à l'aide de vemurafenib, un inhibiteur de BRAF, cette étude montre que des mutations du gène RAS sont fréquentes dans les carcinomes épidermoïdes cutanés et les kératoacanthomes qui se développent chez ces patients

• RAS Mutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors
  • New England Journal of Medicine, Vol. 366 (3), pp. 207-215, 2012 (résumé)
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  Menée sur 21 échantillons tumoraux prélevés sur des patients traités à l'aide de vemurafenib, un inhibiteur de BRAF, cette étude montre que des mutations du gène RAS sont fréquentes dans les carcinomes épidermoïdes cutanés et les kératoacanthomes qui se développent chez ces patients

  “RAS Mutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors”

  • Su, Fei;Viros, Amaya;Milagre, Carla;Trunzer, Kerstin;Bollag, Gideon;Spleiss, Olivia;Reis-Filho, Jorge S.;Kong, Xiangju;Koya, Richard C.;Flaherty, Keith T.;Chapman, Paul B.;Kim, Min Jung;Hayward, Robert;Martin, Matthew;Yang, Hong;Wang, Qiongqing;Hilton, Holly;Hang, Julie S.;Noe, Johannes;Lambros, Maryou;Geyer, Felipe;Dhomen, Nathalie;Niculescu-Duvaz, Ion;Zambon, Alfonso;Niculescu-Duvaz, Dan;Preece, Natasha;Robert, Lídia;Otte, Nicholas J.;Mok, Stephen;Kee, Damien;Ma, Yan;Zhang, Chao;Habets, Gaston;Burton, Elizabeth A.;Wong, Bernice;Nguyen, Hoa;Kockx, Mark;Andries, Luc;Lestini, Brian;Nolop, Keith B.;Lee, Richard J.;Joe, Andrew K.;Troy, James L.;Gonzalez, Rene;Hutson, Thomas E.;Puzanov, Igor;Chmielowski, Bartosz;Springer, Caroline J.;McArthur, Grant A.;Sosman, Jeffrey A.;Lo, Roger S.;Ribas, Antoni;Marais, Richard

  Background: Cutaneous squamous-cell carcinomas and keratoacanthomas are common findings in patients treated with BRAF inhibitors. Methods: We performed a molecular analysis to identify oncogenic mutations (HRAS, KRAS, NRAS, CDKN2A, and TP53) in the lesions from patients treated with the BRAF inhibitor vemurafenib. An analysis of an independent validation set and functional studies with BRAF inhibitors in the presence of the prevalent RAS mutation was also performed. Results: Among 21 tumor samples, 13 had RAS mutations (12 in HRAS). In a validation set of 14 samples, 8 had RAS mutations (4 in HRAS). Thus, 60% (21 of 35) of the specimens harbored RAS mutations, the most prevalent being HRAS Q61L. Increased proliferation of HRAS Q61L–mutant cell lines exposed to vemurafenib was associated with mitogen-activated protein kinase (MAPK)–pathway signaling and activation of ERK-mediated transcription. In a mouse model of HRAS Q61L–mediated skin carcinogenesis, the vemurafenib analogue ...

  
  
• RAF around the Edges — The Paradox of BRAF Inhibitors
  • New England Journal of Medicine, Vol. 366 (3), pp. 271-273, 2012 (éditorial)
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  Menée sur 21 échantillons tumoraux prélevés sur des patients traités à l'aide de vemurafenib, un inhibiteur de BRAF, cette étude montre que des mutations du gène RAS sont fréquentes dans les carcinomes épidermoïdes cutanés et les kératoacanthomes qui se développent chez ces patients

  “RAF around the Edges — The Paradox of BRAF Inhibitors”

  • Weeraratna, Ashani T.

  
  

Mots clés : Peau (hors mélanome); Traitements (Traitements systémiques : découverte et développement)

Mené sur 22 patients atteints d'un carcinome épidermoïde cutané agressif, cet essai de phase II évalue le gefinitib en traitement néoadjuvant

• A Phase II Study of Gefitinib for Aggressive Cutaneous Squamous Cell Carcinoma of the Head and Neck
  • Clinical Cancer Research, sous presse, 2012 (résumé)
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  Mené sur 22 patients atteints d'un carcinome épidermoïde cutané agressif, cet essai de phase II évalue le gefinitib en traitement néoadjuvant

  “A Phase II Study of Gefitinib for Aggressive Cutaneous Squamous Cell Carcinoma of the Head and Neck”

  • Lewis, Carol M;Glisson, Bonnie S.;Feng, Lei;Wan, Fiona;Tang, Ximing;Wistuba, Ignacio I.;El-Naggar, Adel K.;Rosenthal, David I;Chambers, Mark S;lustig, robert A.;Weber, Randal S

  Purpose: To determine the disease control rate and toxicity of treating patients with aggressive cutaneous squamous cell carcinoma (CSCC) with neoadjuvant gefitinib. Experimental Design: A prospective phase II clinical trial evaluating neoadjuvant gefitinib given prior to standard treatment with surgery and/or radiotherapy. Patients with stable disease after 1 cycle received escalated doses. Patients who responded were given gefitinib during radiation therapy, as well as maintenance therapy after definitive treatment. We analyzed the correlation between EGFR expression, mutation status, and gene copy number on available tissue samples and clinical response. Results: Twenty-three patients were accrued and 22 patients were evaluable for response prior to definitive local treatment; complete responses were attained by 18.2% of patients and partial responses by 27.3%. Grade 2-3 toxicities were observed in 59.1% of patients experiencing class-specific effects during induction therapy. ...

  
  

Mots clés : Peau (hors mélanome); Traitements (Traitements systémiques : découverte et développement)

Cette étude analyse les mécanismes associés à l'efficacité de l'alemtuzumab à faible dose chez des patients atteints de certaines formes de lymphome cutané à cellules T

• Skin Effector Memory T Cells Do Not Recirculate and Provide Immune Protection in Alemtuzumab-Treated CTCL Patients
  • Science Translational Medicine, Vol. 4 (117), pp. 117ra7, 2012 (résumé)
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  Cette étude analyse les mécanismes associés à l'efficacité de l'alemtuzumab à faible dose chez des patients atteints de certaines formes de lymphome cutané à cellules T

  “Skin Effector Memory T Cells Do Not Recirculate and Provide Immune Protection in Alemtuzumab-Treated CTCL Patients”

  • Clark, Rachael A.;Watanabe, Rei;Teague, Jessica E.;Schlapbach, Christoph;Tawa, Marianne C.;Adams, Natalie;Dorosario, Andrew A.;Chaney, Keri S.;Cutler, Corey S.;LeBoeuf, Nicole R.;Carter, Joi B.;Fisher, David C.;Kupper, Thomas S.

  Cutaneous T cell lymphoma (CTCL) is a cancer of skin-homing T cells with variants that include leukemic CTCL (L-CTCL), a malignancy of central memory T cells (TCM), and mycosis fungoides (MF), a malignancy of skin resident effector memory T cells (TEM). We report that low-dose alemtuzumab (αCD52) effectively treated patients with refractory L-CTCL but not MF. Alemtuzumab depleted all T cells in blood and depleted both benign and malignant TCM from skin, but a diverse population of skin resident TEM remained in skin after therapy. T cell depletion with alemtuzumab required the presence of neutrophils, a cell type frequent in blood but rare in normal skin. These data suggest that TCM were depleted because they recirculate between the blood and the skin, whereas skin resident TEM were spared because they are sessile and non-recirculating. After alemtuzumab treatment, skin T cells produced lower amounts of interleukin-4 and higher amounts of interferon-γ. Moreover, there was a marked ...

  
  

Mots clés : Lymphome; Traitements (Traitements systémiques : découverte et développement)

Mené sur 15 patients atteints d'une leucémie B lymphoblastique aiguë HER2+ récidivante ou réfractaire (âge médian : 62 ans), cet essai de phase II évalue l'efficacité et la toxicité du trastuzumab

• Trastuzumab for treatment of refractory/relapsed HER2-positive adult B-ALL: results of a phase II GRAALL study
  • Blood, sous presse, 2012 (résumé)
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  Mené sur 15 patients atteints d'une leucémie B lymphoblastique aiguë HER2+ récidivante ou réfractaire (âge médian : 62 ans), cet essai de phase II évalue l'efficacité et la toxicité du trastuzumab

  “Trastuzumab for treatment of refractory/relapsed HER2-positive adult B-ALL: results of a phase II GRAALL study”

  • Chevallier, Patrice;Robillard, Nelly;Charbonnier, Aude;Raffoux, Emmanuel;Maury, Sebastien;Carras, Sylvain;Chabrot, Cecile;Fohrer, Cecile;Bernard, Marc;Blade, Jean-Sebastien;Etienne, Anne;Talmant, Pascaline;Delaunay, Jacques;Guillaume, Thierry;Mohty, Mohamad;Bene, Marie-Christine;Ifrah, Norbert;Dombret, Herve

  The aim of this Phase II study was to evaluate the efficacy and safety of trastuzumab, a humanized monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2), for adult patients with relapsed/refractory HER2-positive B-ALL. Fifteen patients, with a median age of 62 years, received trastuzumab according to the schedule approved for breast cancer patients i.e. 4 mg/kg intravenous loading dose followed by 2 mg/kg weekly. The overall response rate was 13% with two patients achieving partial response and partial remission cytolytic response, respectively. Two other patients were documented with blast clearance. Only one reversible grade 3 cardiac toxic event occurred. This Phase II study showed that trastuzumab monotherapy can allow for some responses in a very high-risk refractory/relapsed HER2-positive adult B-ALL population. Combination of trastuzumab with chemotherapy or other therapeutic monoclonal antibodies should be tested in the future. The trial was ...

  
  

Mots clés : Leucémie; Traitements (Traitements systémiques : découverte et développement)

Menée in vitro et in vivo, cette étude suggère l'efficacité d'un traitement combinant un inhibiteur de RAF, le vemurafenib, et un inhibiteur d'EGFR chez les patients atteints d'un cancer colorectal présentant des mutations du gène BRAF

• EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition
  • Cancer Discovery, sous presse, 2012 (résumé)
  Détails

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  Menée in vitro et in vivo, cette étude suggère l'efficacité d'un traitement combinant un inhibiteur de RAF, le vemurafenib, et un inhibiteur d'EGFR chez les patients atteints d'un cancer colorectal présentant des mutations du gène BRAF

  “EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition”

  • Corcoran, Ryan B;Ebi, Hiromichi;Turke, Alexa B;Coffee, Erin M;Nishino, Michiya;Cogdill, Alexandria P;Brown, Ronald D;Della Pelle, Patricia;Dias-Santagata, Dora;Hung, Kenneth E;Flaherty, Keith T;Piris, Adriano;Wargo, Jennifer A;Settleman, Jeffrey;Mino-Kenudsen, Mari;Engelman, Jeffrey A

  BRAF mutations occur in 10-15% of colorectal cancers (CRCs) and confer adverse outcome. While RAF inhibitors such as vemurafenib (PLX4032) have proven effective in BRAF mutant melanoma, they are surprisingly ineffective in BRAF mutant CRCs, and the reason for this disparity remains unclear. Compared to BRAF mutant melanoma cells, BRAF mutant CRC cells were less sensitive to vemurafenib, and P-ERK suppression was not sustained in response to treatment. Although transient inhibition of phospho-ERK by vemurafenib was observed in CRC, rapid ERK re-activation occurred through EGFR-mediated activation of RAS and CRAF. BRAF mutant CRCs expressed higher levels of phospho-EGFR than BRAF mutant melanomas, suggesting that CRCs are specifically poised for EGFR-mediated resistance. Combined RAF and EGFR inhibition blocked reactivation of MAPK signaling in BRAF mutant CRC cells and markedly improved efficacy in vitro and in vivo. These findings support evaluation of combined RAF and EGFR inhibition ...

  
  

Mots clés : Colon-rectum; Traitements (Traitements systémiques : découverte et développement)

Cet article passe en revue les travaux récents sur le rôle des sous-unités individuelles du facteur NF-κB dans le développement d'un cancer et analyse les perspectives offertes par le ciblage de ces molécules pour la mise au point de nouveaux traitements

• The diverse and complex roles of NF-κB subunits in cancer
  • Nature Reviews Cancer, sous presse, 2012 (résumé)
  Détails

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  Cet article passe en revue les travaux récents sur le rôle des sous-unités individuelles du facteur NF-κB dans le développement d'un cancer et analyse les perspectives offertes par le ciblage de ces molécules pour la mise au point de nouveaux traitements

  “The diverse and complex roles of NF-κB subunits in cancer”

  • Perkins, Neil D.

  It is only recently that the full importance of nuclear factor- κB (NF-κB) signalling to cancer development has been understood. Although much attention has focused on the upstream pathways leading to NF-κB activation, it is now becoming clear that the inhibitor of NF-κB kinases (IKKs), which regulate NF-κB activation, have many independent functions in tissue homeostasis and normal immune function that could compromise the clinical utility of IKK inhibitors. Therefore, if the NF-κB pathway is to be properly exploited as a target for both anticancer and anti-inflammatory drugs, it is appropriate to reconsider the complex roles of the individual NF-κB subunits.

  
  

Mots clés : Cancer (général); Traitements (Traitements systémiques : découverte et développement)

Mené sur 54 patients atteints de divers types de cancer de stade avancé (âge moyen : 56 ans), cet essai de phase I évalue un traitement combinant docétaxel et aflibercept en injection intraveineuse

• Phase I Dose-Escalation Study of Intravenous Aflibercept in Combination With Docetaxel in Patients With Advanced Solid Tumors
  • Clinical Cancer Research, sous presse, 2012 (résumé)
  Détails

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  Mené sur 54 patients atteints de divers types de cancer de stade avancé (âge moyen : 56 ans), cet essai de phase I évalue un traitement combinant docétaxel et aflibercept en injection intraveineuse

  “Phase I Dose-Escalation Study of Intravenous Aflibercept in Combination With Docetaxel in Patients With Advanced Solid Tumors”

  • Isambert, Nicolas;Freyer, Gilles J.;Zanetta, Sylvie;You, Benoît;Fumoleau, Pierre;Falandry, Claire;Favier, Laure;Assadourian, Sylvie;Soussan-Lazard, Karen;Ziti-Ljajic, Samira;Trillet-Lenoir, Véronique

  Purpose: This phase I study cohort investigated aflibercept in combination with docetaxel in patients with advanced solid tumors. Materials and Methods: Eligible patients had metastatic or nonresectable cancer for which docetaxel was considered appropriate. Patients received intravenous aflibercept 2, 4, 5, 6, 7 or 9 mg/kg with docetaxel 75 mg/m2 on day 1 every-3-weeks until disease progression or unacceptable toxicity. Primary objectives were to evaluate dose-limiting toxicities (DLTs) during cycle 1 and to determine the aflibercept recommended phase II trial dose (RP2D) for combination with docetaxel. Pharmacokinetics, tolerability and antitumor activity were also investigated. Results: Fifty-four patients (mean age, 56 years) were enrolled. Most had prior chemotherapy (96%) and most (24.1%) had breast cancer. In the dose-escalation phase (n=34), there were 3 DLTs: grade 4 neutropenic infection (2 mg/kg), grade 3 dysphonia (7 mg/kg) and grade 2 hypertension (9 mg/kg). An excess of ...

  
  

Mots clés : Cancer (général); Traitements (Traitements systémiques : découverte et développement)

Menée sur 4 657 patientes atteintes d'un cancer du sein et incluses dans la cohorte "Intergroup Exemestane Study" (durée médiane de suivi : 91 mois), cette étude évalue l'incidence des troubles musculo-squelettiques, notamment le syndrome du canal carpien, en fonction d'un traitement adjuvant au tamoxifène ou à l'exémestane

• Carpal tunnel syndrome and musculoskeletal symptoms in postmenopausal women with early breast cancer treated with exemestane or tamoxifen after 2?3 years of tamoxifen: a retrospective analysis of the Intergroup Exemestane Study
  • The Lancet Oncology, sous presse, 2012 (résumé)
  Détails

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  Menée sur 4 657 patientes atteintes d'un cancer du sein et incluses dans la cohorte "Intergroup Exemestane Study" (durée médiane de suivi : 91 mois), cette étude évalue l'incidence des troubles musculo-squelettiques, notamment le syndrome du canal carpien, en fonction d'un traitement adjuvant au tamoxifène ou à l'exémestane

  “Carpal tunnel syndrome and musculoskeletal symptoms in postmenopausal women with early breast cancer treated with exemestane or tamoxifen after 2?3 years of tamoxifen: a retrospective analysis of the Intergroup Exemestane Study”

  • Mieog, J. Sven D.;Morden, James P.;Bliss, Judith M.;Coombes, R. Charles;van de Velde, Cornelis J. H.

  Aromatase inhibitors are more effective than is tamoxifen in prevention of breast-cancer recurrence, but at the expense of increased musculoskeletal side-effects, such as carpal tunnel syndrome. The aim of this study was to assess risk factors and the prognostic value of musculoskeletal symptoms during treatment with the steroidal aromatase inhibitor exemestane or with tamoxifen after 2?3 years of tamoxifen. In the Intergroup Exemestane Study, postmenopausal women treated for early invasive breast cancer who remained disease free and on treatment after 2?3 years of tamoxifen were randomised to switch to exemestane or to continue tamoxifen for the remainder of the 5-year period of endocrine treatment. The primary endpoint for this retrospective analysis was occurrence of carpal tunnel syndrome and any musculoskeletal events, analysed in the safety population, which consisted of all patients who had received any trial treatment. As well as case-report forms, questionnaires were ...

  
  
• Aromatase inhibitors and musculoskeletal adverse events
  • The Lancet Oncology, sous presse, 2012 (commentaire en libre accès)
  Détails

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  Menée sur 4 657 patientes atteintes d'un cancer du sein et incluses dans la cohorte "Intergroup Exemestane Study" (durée médiane de suivi : 91 mois), cette étude évalue l'incidence des troubles musculo-squelettiques, notamment le syndrome du canal carpien, en fonction d'un traitement adjuvant au tamoxifène ou à l'exémestane

  “Aromatase inhibitors and musculoskeletal adverse events”

  • Liedke, Pedro E. R. ; Goss, Paul E.

  
  

Mots clés : Sein; Traitements (Traitements systémiques : applications cliniques)

Mené sur 201 patientes atteintes d'un cancer du sein ER+/HER2-avant la ménopause, cet essai de phase III évalue l'ajout de tamoxifène ou d'anastrozole à un traitement néoadjuvant par goséréline

• Neoadjuvant anastrozole versus tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): a double-blind, randomised phase 3 trial
  • The Lancet Oncology, sous presse, 2012 (résumé)
  Détails

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  Mené sur 201 patientes atteintes d'un cancer du sein ER+/HER2-avant la ménopause, cet essai de phase III évalue l'ajout de tamoxifène ou d'anastrozole à un traitement néoadjuvant par goséréline

  “Neoadjuvant anastrozole versus tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): a double-blind, randomised phase 3 trial”

  • Masuda, Norikazu;Sagara, Yasuaki;Kinoshita, Takayuki;Iwata, Hiroji;Nakamura, Seigo;Yanagita, Yasuhiro;Nishimura, Reiki;Iwase, Hirotaka;Kamigaki, Shunji;Takei, Hiroyuki;Noguchi, Shinzaburo

  Aromatase inhibitors have shown increased efficacy compared with tamoxifen in postmenopausal early breast cancer. We aimed to assess the efficacy and safety of anastrozole versus tamoxifen in premenopausal women receiving goserelin for early breast cancer in the neoadjuvant setting. In this phase 3, randomised, double-blind, parallel-group, multicentre study, we enrolled premenopausal women with oestrogen receptor (ER)-positive, HER2-negative, operable breast cancer with WHO performance status of 2 or lower. Patients were randomly assigned (1:1) to receive goserelin 3·6 mg/month plus either anastrozole 1 mg per day and tamoxifen placebo or tamoxifen 20 mg per day and anastrozole placebo for 24 weeks before surgery. Patients were randomised sequentially, stratified by centre, with randomisation codes. All study personnel were masked to study treatment. The primary endpoint was best overall tumour response (complete response or partial response), assessed by callipers, during the ...

  
  
• Aromatase inhibitors in premenopausal breast cancer
  • The Lancet Oncology, sous presse, 2012 (commentaire en libre accès)
  Détails

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  Mené sur 201 patientes atteintes d'un cancer du sein ER+/HER2-avant la ménopause, cet essai de phase III évalue l'ajout de tamoxifène ou d'anastrozole à un traitement néoadjuvant par goséréline

  “Aromatase inhibitors in premenopausal breast cancer”

  • Kelly, Catherine M. ; Buzdar, Aman U.

  
  

Mots clés : Sein; Traitements (Traitements systémiques : applications cliniques)

Mené sur 455 patientes atteintes d'un cancer du sein HER2+, cet essai de phase III évalue l'intérêt, du point de vue du critère de réponse pathologique complète, d'un traitement néoadjuvant combinant lapatinib et trastuzumab

• Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial
  • The Lancet, sous presse, 2012 (résumé)
  Détails

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  Mené sur 455 patientes atteintes d'un cancer du sein HER2+, cet essai de phase III évalue l'intérêt, du point de vue du critère de réponse pathologique complète, d'un traitement néoadjuvant combinant lapatinib et trastuzumab

  “Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial”

  • Baselga, José;Bradbury, Ian;Eidtmann, Holger;Di Cosimo, Serena;de Azambuja, Evandro;Aura, Claudia;Gómez, Henry;Dinh, Phuong;Fauria, Karine;Van Dooren, Veerle;Aktan, Gursel;Goldhirsch, Aron;Chang, Tsai-Wang;Horváth, Zsolt;Coccia-Portugal, Maria;Domont, Julien;Tseng, Ling-Min;Kunz, Georg;Sohn, Joo Hyuk;Semiglazov, Vladimir;Lerzo, Guillermo;Palacova, Marketa;Probachai, Volodymyr;Pusztai, Lajos;Untch, Michael;Gelber, Richard D.;Piccart-Gebhart, Martine

  The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer. We argue that the two anti-HER2 agents given together would be better than single-agent therapy. In this parallel groups, randomised, open-label, phase 3 study undertaken between Jan 5, 2008, and May 27, 2010, women from 23 countries with HER2-positive primary breast cancer with tumours greater than 2 cm in diameter were randomly assigned to oral lapatinib (1500 mg), intravenous trastuzumab (loading dose 4 mg/m2, subsequent doses 2 mg/kg), or lapatinib (1000 mg) plus trastuzumab. Treatment allocation was by stratified, permuted blocks randomisation, with four stratification factors. Anti-HER2 therapy alone was given for the first 6 weeks; weekly paclitaxel (80 mg/m2) was then added to the regimen for a further 12 weeks, before definitive surgery was undertaken. After ...

  
  
• Dual inhibition of HER2 in breast cancer treatment
  • The Lancet, sous presse, 2012 (commentaire)
  Détails

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  Mené sur 455 patientes atteintes d'un cancer du sein HER2+, cet essai de phase III évalue l'intérêt, du point de vue du critère de réponse pathologique complète, d'un traitement néoadjuvant combinant lapatinib et trastuzumab

  “Dual inhibition of HER2 in breast cancer treatment”

  • Gnant, Michael ; Steger, Guenther G.

  
  

Mots clés : Sein; Traitements (Traitements systémiques : applications cliniques)

Menée sur 302 patients atteints d'un cancer de la prostate à faible risque et ayant opté pour une surveillance active, cette étude américaine évalue l'efficacité et la toxicité du dutastéride, un inhibiteur de 5-alpha-réductase, pour ralentir la progression de la maladie (durée de suivi : 3 ans)

• Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial
  • The Lancet, sous presse, 2012 (résumé)
  Détails

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  Menée sur 302 patients atteints d'un cancer de la prostate à faible risque et ayant opté pour une surveillance active, cette étude américaine évalue l'efficacité et la toxicité du dutastéride, un inhibiteur de 5-alpha-réductase, pour ralentir la progression de la maladie (durée de suivi : 3 ans)

  “Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial”

  • Fleshner, Neil E.;Lucia, M. Scott;Egerdie, Blair;Aaron, Lorne;Eure, Gregg;Nandy, Indrani;Black, Libby;Rittmaster, Roger S.

  We aimed to investigate the safety and efficacy of dutasteride, a 5?-reductase inhibitor, on prostate cancer progression in men with low-risk disease who chose to be followed up with active surveillance. In our 3 year, randomised, double-blind, placebo-controlled study, undertaken at 65 academic medical centres or outpatient clinics in North America, we enrolled men aged 48?82 years who had low-volume, Gleason score 5?6 prostate cancer and had chosen to be followed up with active surveillance. We randomly allocated participants in a one-to-one ratio, stratified by site and in block sizes of four, to receive once-daily dutasteride 0·5 mg or matching placebo. Participants were followed up for 3 years, with 12-core prostate biopsy samples obtained after 18 months and 3 years. The primary endpoint was time to prostate cancer progression, defined as the number of days between the start of study treatment and the earlier of either pathological progression (in patients with ?1 biopsy ...

  
  
• What (if anything) to do about low-risk prostate cancer
  • The Lancet, sous presse, 2012 (commentaire)
  Détails

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  Menée sur 302 patients atteints d'un cancer de la prostate à faible risque et ayant opté pour une surveillance active, cette étude américaine évalue l'efficacité et la toxicité du dutastéride, un inhibiteur de 5-alpha-réductase, pour ralentir la progression de la maladie (durée de suivi : 3 ans)

  “What (if anything) to do about low-risk prostate cancer”

  • Parker, Chris

  
  

Mots clés : Prostate; Traitements (Traitements systémiques : applications cliniques)

Mené sur 2 590 patients dans 77 centres hospitaliers de 24 pays, cet essai de phase III compare l'efficacité et la toxicité de l'erlotinib par rapport au docétaxel ou au pemetrexed pour le traitement de deuxième ligne d'un cancer du poumon non à petites cellules

• Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study
  • The Lancet Oncology, sous presse, 2012 (résumé)
  Détails

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  Mené sur 2 590 patients dans 77 centres hospitaliers de 24 pays, cet essai de phase III compare l'efficacité et la toxicité de l'erlotinib par rapport au docétaxel ou au pemetrexed pour le traitement de deuxième ligne d'un cancer du poumon non à petites cellules

  “Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study”

  • Ciuleanu, Tudor;Stelmakh, Lilia;Cicenas, Saulius;Miliauskas, Skaidrius;Grigorescu, Alexandru Calin;Hillenbach, Carina;Johannsdottir, Hrefna Kristin;Klughammer, Barbara;Gonzalez, Emilio Esteban

  Erlotinib, docetaxel, and pemetrexed are approved for the second-line treatment of non-small-cell lung cancer (NSCLC), but no head-to-head data from large clinical trials are available. We undertook the Tarceva In Treatment of Advanced NSCLC (TITAN) study to assess the efficacy and tolerability of second-line erlotinib versus chemotherapy in patients with refractory NSCLC. TITAN was an international, randomised multicentre, open-label, phase 3 study that was done at 77 sites in 24 countries. Chemotherapy-naive patients with locally advanced, recurrent, or metastatic NSCLC received up to four cycles of first-line platinum doublet chemotherapy, after which patients with disease progression during or immediately after chemotherapy were offered enrolment into TITAN. Enrolled patients were randomly assigned (1:1) by a minimisation method to ensure balanced stratification, to receive erlotinib 150 mg/day or chemotherapy (standard docetaxel or pemetrexed regimens, at the treating ...

  
  
• Beyond first-line NSCLC therapy: chemotherapy or erlotinib?
  • The Lancet Oncology, sous presse, 2012 (commentaire en libre accès)
  Détails

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  Mené sur 2 590 patients dans 77 centres hospitaliers de 24 pays, cet essai de phase III compare l'efficacité et la toxicité de l'erlotinib par rapport au docétaxel ou au pemetrexed pour le traitement de deuxième ligne d'un cancer du poumon non à petites cellules

  “Beyond first-line NSCLC therapy: chemotherapy or erlotinib?”

  • Paz-Ares, Luis

  
  

Mots clés : Poumon; Traitements (Traitements systémiques : applications cliniques)

Cet article passe en revue les travaux récents sur le traitement néoadjuvant d'un cancer du pancréas

• Neoadjuvant Therapy of Pancreatic Cancer: The Emerging Paradigm?
  • The Oncologist, sous presse, 2012 (résumé)
  Détails

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  Cet article passe en revue les travaux récents sur le traitement néoadjuvant d'un cancer du pancréas

  “Neoadjuvant Therapy of Pancreatic Cancer: The Emerging Paradigm?”

  • Lim, Kian-Huat;Chung, Eugene;Khan, Adeel;Cao, Dengfeng;Linehan, David;Ben-Josef, Edgar;Wang-Gillam, Andrea

  Abstract Pancreatic cancer remains one of the deadliest cancers due to difficulty in early diagnosis and its high resistance to chemotherapy and radiation. It is now clear that even patients with potentially resectable disease require multimodality treatment including chemotherapy and/or radiation to improve resectability and reduce recurrence. Tremendous efforts are currently being invested in refining preoperative staging to identify optimal surgical candidates, and also in developing various neoadjuvant or adjuvant regimens to improve surgical outcome. Although at present no studies have been done to directly compare the benefit of neoadjuvant versus adjuvant approaches, accumulating evidence suggests that the neoadjuvant approach is probably beneficial for a subset of the patient population, particularly those with borderline resectable disease in which complete surgical resection is almost certainly unachievable. In this article, we review the literature and rationales of ...

  
  

Mots clés : Pancréas; Traitements (Traitements systémiques : applications cliniques)

A partir de données issues des registres américains du cancer et de diverses bases de données d'assurance maladie entre 2004 et 2009, cette étude évalue les effets d'un ajout d'oxaliplatine à un traitement adjuvant par 5-fluorouracile sur la survie globale

• Comparative Effectiveness of Oxaliplatin vs Non–Oxaliplatin-containing Adjuvant Chemotherapy for Stage III Colon Cancer
  • Journal of the National Cancer Institute, sous presse, 2012 (résumé)
  Détails

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  A partir de données issues des registres américains du cancer et de diverses bases de données d'assurance maladie entre 2004 et 2009, cette étude évalue les effets d'un ajout d'oxaliplatine à un traitement adjuvant par 5-fluorouracile sur la survie globale

  “Comparative Effectiveness of Oxaliplatin vs Non–Oxaliplatin-containing Adjuvant Chemotherapy for Stage III Colon Cancer”

  • Sanoff, Hanna K.;Carpenter, William R.;Martin, Christopher F.;Sargent, Daniel J.;Meyerhardt, Jeffrey A.;Stürmer, Til;Fine, Jason P.;Weeks, Jane;Niland, Joyce;Kahn, Katherine L.;Schymura, Maria J.;Schrag, Deborah

  Background The addition of oxaliplatin to adjuvant 5-fluorouracil (5-FU) improves survival of patients with stage III colon cancer in randomized clinical trials (RCTs). However, RCT participants are younger, healthier, and less racially diverse than the general cancer population. Thus, the benefit of oxaliplatin outside RCTs is uncertain.Subjects and Methods Patients younger than 75 years with stage III colon cancer who received chemotherapy within 120 days of surgical resection were identified from five observational data sources—the Surveillance, Epidemiology, and End Results registry linked to Medicare claims (SEER–Medicare), the New York State Cancer Registry (NYSCR) linked to Medicaid and Medicare claims, the National Comprehensive Cancer Network (NCCN) Outcomes Database, and the Cancer Care Outcomes Research & Surveillance Consortium (CanCORS). Overall survival (OS) was compared among patients treated with oxaliplatin vs non–oxaliplatin-containing adjuvant chemotherapy. ...

  
  
• Study Showed Oxaliplatin Improved Colon Cancer Patient Survival
  • Journal of the National Cancer Institute, sous presse, 2012 (communiqué de presse)
  Détails

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  A partir de données issues des registres américains du cancer et de diverses bases de données d'assurance maladie entre 2004 et 2009, cette étude évalue les effets d'un ajout d'oxaliplatine à un traitement adjuvant par 5-fluorouracile sur la survie globale

  “Study Showed Oxaliplatin Improved Colon Cancer Patient Survival”

  
  

Mots clés : Colon-rectum; Traitements (Traitements systémiques : applications cliniques)

A partir de données issues des registres américains du cancer et de la base Medicare et portant sur 2 526 patients atteints d'un cancer colorectal de stade IV entre 2002 et 2007, cette étude évalue l'ajout de bevacizumab à divers agents de chimiothérapie de première ligne

• Effectiveness of Bevacizumab With First-Line Combination Chemotherapy for Medicare Patients With Stage IV Colorectal Cancer
  • Journal of Clinical Oncology, sous presse, 2012 (résumé)
  Détails

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  A partir de données issues des registres américains du cancer et de la base Medicare et portant sur 2 526 patients atteints d'un cancer colorectal de stade IV entre 2002 et 2007, cette étude évalue l'ajout de bevacizumab à divers agents de chimiothérapie de première ligne

  “Effectiveness of Bevacizumab With First-Line Combination Chemotherapy for Medicare Patients With Stage IV Colorectal Cancer”

  • Meyerhardt, Jeffrey A.;Li, Ling;Sanoff, Hanna K.;Carpenter, William;Schrag, Deborah

  Purpose Clinical trials have shown that adding bevacizumab to cytotoxic chemotherapy improves survival for patients with colorectal cancer, although its effectiveness in the Medicare population is uncertain.Patients and Methods Using the Surveillance, Epidemiology, and End Results (SEER) -Medicare linked database, we identified 2,526 patients with stage IV colorectal cancer diagnosed between 2002 and 2007 who received first-line combination chemotherapy with a fluoropyrimidine and either irinotecan (33%) or oxaliplatin (67%). Thirty-six percent of patients received bevacizumab with first-line therapy. The primary outcome was overall survival. Secondary outcomes were bevacizumab-associated toxicities, including the incidence of stroke, myocardial infarction, and GI perforation.Results In the primary cohort inclusive of patients diagnosed between 2002 and 2007, bevacizumab with combination chemotherapy was associated with improved overall survival (adjusted hazard ratio [HR], 0.85; 95% ...

  
  
• Registries and Randomized Trials in Assessing the Effects of Bevacizumab in Colorectal Cancer: Is There a Common Theme?
  • Journal of Clinical Oncology, sous presse, 2012 (éditorial en libre accès)
  Détails

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  A partir de données issues des registres américains du cancer et de la base Medicare et portant sur 2 526 patients atteints d'un cancer colorectal de stade IV entre 2002 et 2007, cette étude évalue l'ajout de bevacizumab à divers agents de chimiothérapie de première ligne

  “Registries and Randomized Trials in Assessing the Effects of Bevacizumab in Colorectal Cancer: Is There a Common Theme?”

  • Hurwitz, Herbert I. ; Lyman, Gary H.

  
  

Mots clés : Colon-rectum; Traitements (Traitements systémiques : applications cliniques)

Mené sur 840 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade III / IV et non métastatique (durée médiane de suivi : 5,2 ans), cet essai ouvert randomisé de phase III compare l'efficacité et la toxicité d'une chimioradiothérapie conventionnelle et d'une radiothérapie accélérée combinée ou non à une chimiothérapie concomitante

• Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial
  • The Lancet Oncology, sous presse, 2012 (résumé)
  Détails

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  Mené sur 840 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade III / IV et non métastatique (durée médiane de suivi : 5,2 ans), cet essai ouvert randomisé de phase III compare l'efficacité et la toxicité d'une chimioradiothérapie conventionnelle et d'une radiothérapie accélérée combinée ou non à une chimiothérapie concomitante

  “Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial”

  • Bourhis, Jean;Sire, Christian;Graff, Pierre;Grégoire, Vincent;Maingon, Philippe;Calais, Gilles;Gery, Bernard;Martin, Laurent;Alfonsi, Marc;Desprez, Patrick;Pignon, Thierry;Bardet, Etienne;Rives, Michel;Geoffrois, Lionel;Daly-Schveitzer, Nicolas;Sen, Sok;Tuchais, Claude;Dupuis, Olivier;Guerif, Stéphane;Lapeyre, Michel;Favrel, Véronique;Hamoir, Marc;Lusinchi, Antoine;Temam, Stéphane;Pinna, Antonella;Tao, Yun Gan;Blanchard, Pierre;Aupérin, Anne

  Concomitant chemoradiotherapy and accelerated radiotherapy independently improve outcomes for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC). We aimed to assess the efficacy and safety of a combination of these approaches. In our open-label phase 3 randomised trial, we enrolled patients with locally advanced, stage III and IV (non-metastatic) HNSCC and an Eastern Cooperative Oncology Group performance status of 0?2. We randomly allocated patients centrally with a computer program (with centre, T stage, N stage, and localisation as minimisation factors) in a 1:1:1 ratio to receive conventional chemoradiotherapy (70 Gy in 7 weeks plus three cycles of 4 days' concomitant carboplatin-fluorouracil), accelerated radiotherapy-chemotherapy (70 Gy in 6 weeks plus two cycles of 5 days' concomitant carboplatin-fluorouracil), or very accelerated radiotherapy alone (64·8 Gy [1·8 Gy twice daily] in 3·5 weeks). The primary endpoint, progression-free survival (PFS), ...

  
  
• Easing acceleration of head and neck chemoradiotherapy
  • The Lancet Oncology, sous presse, 2012 (commentaire)
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  Mené sur 840 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade III / IV et non métastatique (durée médiane de suivi : 5,2 ans), cet essai ouvert randomisé de phase III compare l'efficacité et la toxicité d'une chimioradiothérapie conventionnelle et d'une radiothérapie accélérée combinée ou non à une chimiothérapie concomitante

  “Easing acceleration of head and neck chemoradiotherapy”

  • Haigentz, Missak ; Corry, June ; Strojan, Primoz ; Ferlito, Alfio

  
  

Mots clés : Voies aérodigestives supérieures; Traitements (Combinaison de traitements localisés et systémiques)

Cet article décrit des recommandations pour la mise en oeuvre d'essais cliniques de traitements en dehors de leur indication d'autorisation de mise sur le marché chez les patients atteints d'un cancer de stade avancé

• Recommendations for Clinical Trials of Off-Label Drugs Used to Treat Advanced-Stage Cancer
  • Journal of Clinical Oncology, sous presse, 2012 (résumé)
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  Cet article décrit des recommandations pour la mise en oeuvre d'essais cliniques de traitements en dehors de leur indication d'autorisation de mise sur le marché chez les patients atteints d'un cancer de stade avancé

  “Recommendations for Clinical Trials of Off-Label Drugs Used to Treat Advanced-Stage Cancer”

  • Mullins, C. Daniel;Montgomery, Russ;Abernethy, Amy P.;Hussain, Arif;Pearson, Steven D.;Tunis, Sean

  Purpose To provide recommendations to trialists and sponsors that guide the design and implementation of prospective postapproval clinical trials for oncology drugs used outside US Food and Drug Administration–labeled indications for treatment of late-stage cancers.Methods A meeting was hosted by the Center for Medical Technology Policy in Baltimore, MD, on November 12, 2009. Discussions during the meeting and key informant interviews were conducted before and after this stakeholder meeting. Peer review by multidisciplinary stakeholders was followed by a public comment period. Input was received from patient advocacy groups, medical oncologists, pharmaceutical companies, the US Food and Drug Administration, Centers for Medicare and Medicaid Services, the National Cancer Institute, foreign government agencies involved in health technology assessment, public and private payers, drug compendia, clinical research entities, statisticians, academics, and the American Society of Clinical ...

  
  
• Off-Label Use of Oncology Drugs: The Need for More Data and Then Some
  • Journal of Clinical Oncology, sous presse, 2012 (éditorial en libre accès)
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  Cet article décrit des recommandations pour la mise en oeuvre d'essais cliniques de traitements en dehors de leur indication d'autorisation de mise sur le marché chez les patients atteints d'un cancer de stade avancé

  “Off-Label Use of Oncology Drugs: The Need for More Data and Then Some”

  • Pfister, David G.

  
  

Mots clés : Cancer (général); Traitements (Ressources et infrastructures (Traitements))