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Accueil Nota Bene Cancer V2 Numéro 100 du 25 Août 2011 Traitements

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Traitements localisés : applications cliniques

Cet article passe en revue la littérature récente sur la radiothérapie pour le traitement d'un cancer localisé de la prostate

  • Comparative Evaluation of Radiation Treatments for Clinically Localized Prostate Cancer: An Updated Systematic Review
    Annals of Internal Medicine, Vol. 155 (3), pp. 171-178, 2011 (article en libre accès)
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    Cet article passe en revue la littérature récente sur la radiothérapie pour le traitement d'un cancer localisé de la prostate

    “Comparative Evaluation of Radiation Treatments for Clinically Localized Prostate Cancer: An Updated Systematic Review”

    • Bannuru, Raveendhara R.;Dvorak, Tomas;Obadan, Ndidiamaka;Yu, Winifred W.;Patel, Kamal;Chung, Mei;Ip, Stanley

    Background: Radiation therapy is one of many treatment options for patients with prostate cancer.Purpose: To update findings on the clinical and biochemical outcomes of radiation therapies for localized prostate cancer.Data Sources: MEDLINE (2007 through March 2011) and the Cochrane Central Register of Controlled Trials (2007 through March 2011).Study Selection: Published English-language comparative studies involving adults with localized prostate cancer who either had first-line radiation therapy or received no initial treatment.Data Extraction: 6 researchers extracted information on study design, potential bias, sample characteristics, interventions, and outcomes and rated the strength of overall evidence. Data for each study were extracted by 1 reviewer and confirmed by another.Data Synthesis: 75 studies (10 randomized, controlled trials [RCTs] and 65 nonrandomized studies) met the inclusion criteria. No RCTs compared radiation therapy with no treatment or no initial treatment. ...


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

Menées sur des données individuelles issues d'essais cliniques dans des contextes adjuvant et métastatique dans le cancer du sein, ces deux méta-analyses évaluent l'efficacité d'une chimiothérapie à haute dose avec greffe autologue de cellules souches hématopoïétiques

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    Menées sur des données individuelles issues d'essais cliniques dans des contextes adjuvant et métastatique dans le cancer du sein, ces deux méta-analyses évaluent l'efficacité d'une chimiothérapie à haute dose avec greffe autologue de cellules souches hématopoïétiques

    “High-Dose Chemotherapy With Autologous Stem-Cell Support As Adjuvant Therapy in Breast Cancer: Overview of 15 Randomized Trials”

    • Berry, Donald A.;Ueno, Naoto T.;Johnson, Marcella M.;Lei, Xiudong;Caputo, Jean;Rodenhuis, Sjoerd;Peters, William P.;Leonard, Robert C.;Barlow, William E.;Tallman, Martin S.;Bergh, Jonas;Nitz, Ulrike A.;Gianni, Alessandro M.;Basser, Russell L.;Zander, Axel R.;Coombes, R. Charles;Roché, Henri;Tokuda, Yutaka;de Vries, Elisabeth G.E.;Hortobagyi, Gabriel N.;Crown, John P.;Pedrazzoli, Paolo;Bregni, Marco;Demirer, Taner

    Purpose Adjuvant high-dose chemotherapy (HDC) with autologous hematopoietic stem-cell transplantation (AHST) for high-risk primary breast cancer has not been shown to prolong survival. Individual trials have had limited power to show overall benefit or benefits within subsets.Methods We assembled individual patient data from 15 randomized trials that compared HDC versus control therapy without stem-cell support. Prospectively defined primary end points were relapse-free survival (RFS) and overall survival (OS). We compared the effect of HDC versus control by using log-rank tests and proportional hazards regression, and we adjusted for clinically relevant covariates. Subset analyses were by age, number of positive lymph nodes, tumor size, histology, hormone receptor (HmR) status, and human epidermal growth factor receptor 2 (HER2) status.Results Of 6,210 total patients (n = 3,118, HDC; n = 3,092 control), the median age was 46 years; 69% were premenopausal, 29% were postmenopausal, and ...


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    Menées sur des données individuelles issues d'essais cliniques dans des contextes adjuvant et métastatique dans le cancer du sein, ces deux méta-analyses évaluent l'efficacité d'une chimiothérapie à haute dose avec greffe autologue de cellules souches hématopoïétiques

    “High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Transplantation in Metastatic Breast Cancer: Overview of Six Randomized Trials”

    • Berry, Donald A. ; Ueno, Naoto T. ; Johnson, Marcella M. ; Lei, Xiudong ; Caputo, Jean ; Smith, Dori A. ; Yancey, Linda J. ; Crump, Michael ; Stadtmauer, Edward A. ; Biron, Pierre ; Crown, John P. ; Schmid, Peter ; Lotz, Jean-Pierre ; Rosti, Giovanni ; Bregni, Marco ; Demirer, Taner

    Purpose High doses of effective chemotherapy are compelling if they can be delivered safely. Substantial interest in supporting high-dose chemotherapy with bone marrow or autologous hematopoietic stem-cell transplantation in the 1980s and 1990s led to the initiation of randomized trials to evaluate its effect in the treatment of metastatic breast cancer.Methods We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support. We assembled a single database containing individual patient information from these trials. The primary analysis of overall survival was a log-rank test comparing high dose versus control. We also used Cox proportional hazards regression, adjusting for known covariates. We addressed potential treatment differences within subsets of patients.Results The effect of high-dose chemotherapy on overall survival was not statistically different (median, 2.16 ...


  • The Era of High-Dose Chemotherapy for Breast Cancer: Revisiting a Troubled Quest
    Journal of Clinical Oncology, Vol. 29 (24), pp. 3205-3206, 2011 (éditorial en libre accès)
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    Menées sur des données individuelles issues d'essais cliniques dans des contextes adjuvant et métastatique dans le cancer du sein, ces deux méta-analyses évaluent l'efficacité d'une chimiothérapie à haute dose avec greffe autologue de cellules souches hématopoïétiques

    “The Era of High-Dose Chemotherapy for Breast Cancer: Revisiting a Troubled Quest”

    • Borges, Virginia F. ; Elias, Anthony D.


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

Traitements systémiques : découverte et développement

Cet article passe en revue les perspectives offertes par l'immunothérapie pour le traitement des cancers de la prostate

  • Immunotherapy for Prostate Cancer: Biology and Therapeutic Approaches
    Journal of Clinical Oncology, sous presse, 2011 (résumé)
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    Cet article passe en revue les perspectives offertes par l'immunothérapie pour le traitement des cancers de la prostate

    “Immunotherapy for Prostate Cancer: Biology and Therapeutic Approaches”

    • Cha, Edward;Fong, Lawrence

    Although prostate cancer was not historically considered to be a particularly immune-responsive cancer, recent clinical trials have demonstrated that immunotherapy for prostate cancer can lead to improvements in overall survival (OS). These studies include randomized controlled trials with sipuleucel-T and another with PROSTVAC-VF, both of which rely on stimulating the immune system to target prostate proteins. This review discusses the most promising developments over the past year in immune-based therapy for prostate cancer and the opportunities that lie ahead. Recent randomized immunotherapy trials in prostate cancer have demonstrated improvements in OS but without the concomitant improvements in progression-free survival. This uncoupling of survival from clinical response poses challenges to clinical management, because conventional measures of objective response cannot be used to identify patients benefiting from treatment. There is a significant need to identify immunologic or ...


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

Menée à l'aide de xénogreffes, cette étude évalue l'activité antitumorale de petites molécules, appelées curaxines, qui activent p53 et simultanément inhibent NF-kappaB sans engendrer de génotoxicité observable

  • Cancer Drug Discovery Faces the FACT
    Science Translational Medicine, Vol. 3 (95), pp. 95ps34, 2011 (commentaire)
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    Menée à l'aide de xénogreffes, cette étude évalue l'activité antitumorale de petites molécules, appelées curaxines, qui activent p53 et simultanément inhibent NF-kappaB sans engendrer de génotoxicité observable

    “Cancer Drug Discovery Faces the FACT”

    • Draetta, Giulio F.;DePinho, Ronald A.

    In this issue of Science Translational Medicine, Gasparian et al. use a clever cell-based screen to identify a family of DNA-binding small molecules—curaxins—that inhibit tumor cell growth and division. The curaxins’ mechanism of action pinpoints a new chromatin-remodeling factor as a therapeutic target for cancer.


  • Curaxins: Anticancer Compounds That Simultaneously Suppress NF-κB and Activate p53 by Targeting FACT
    Science Translational Medicine, Vol. 3 (95), pp. 95ra74, 2011 (résumé)
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    Menée à l'aide de xénogreffes, cette étude évalue l'activité antitumorale de petites molécules, appelées curaxines, qui activent p53 et simultanément inhibent NF-kappaB sans engendrer de génotoxicité observable

    “Curaxins: Anticancer Compounds That Simultaneously Suppress NF-κB and Activate p53 by Targeting FACT”

    • Gasparian, Alexander V. ; Burkhart, Catherine A. ; Purmal, Andrei A. ; Brodsky, Leonid ; Pal, Mahadeb ; Saranadasa, Madhi ; Bosykh, Dmitry A. ; Commane, Mairead ; Guryanova, Olga A. ; Pal, Srabani ; Safina, Alfiya ; Sviridov, Sergey ; Koman, Igor E. ; Veith, Jean ; Komar, Anton A. ; Gudkov, Andrei V. ; Gurova, Katerina V.

    Effective eradication of cancer requires treatment directed against multiple targets. The p53 and nuclear factor κB (NF-κB) pathways are dysregulated in nearly all tumors, making them attractive targets for therapeutic activation and inhibition, respectively. We have isolated and structurally optimized small molecules, curaxins, that simultaneously activate p53 and inhibit NF-κB without causing detectable genotoxicity. Curaxins demonstrated anticancer activity against all tested human tumor xenografts grown in mice. We report here that the effects of curaxins on p53 and NF-κB, as well as their toxicity to cancer cells, result from “chromatin trapping” of the FACT (facilitates chromatin transcription) complex. This FACT inaccessibility leads to phosphorylation of the p53 Ser392 by casein kinase 2 and inhibition of NF-κB–dependent transcription, which requires FACT activity at the elongation stage. These results identify FACT as a prospective anticancer target enabling ...


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

Mené sur 91 patientes, cet essai de phase II évalue l'olaparib pour le traitement d'un cancer ovarien de haut grade et/ou indifférencié ou d'un cancer du sein triple négatif de stade avancé

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    Mené sur 91 patientes, cet essai de phase II évalue l'olaparib pour le traitement d'un cancer ovarien de haut grade et/ou indifférencié ou d'un cancer du sein triple négatif de stade avancé

    “Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study”

    • Gelmon, Karen A.;Tischkowitz, Marc;Mackay, Helen;Swenerton, Kenneth;Robidoux, André;Tonkin, Katia;Hirte, Hal;Huntsman, David;Clemons, Mark;Gilks, Blake;Yerushalmi, Rinat;Macpherson, Euan;Carmichael, James;Oza, Amit

    Olaparib (AZD2281) is a small-molecule, potent oral poly(ADP-ribose) polymerase (PARP) inhibitor. We aimed to assess the safety and tolerability of this drug in patients withoutBRCA1orBRCA2mutations with advanced triple-negative breast cancer or high-grade serous and/or undifferentiated ovarian cancer. In this phase 2, multicentre, open-label, non-randomised study, women with advanced high-grade serous and/or undifferentiated ovarian carcinoma or triple-negative breast cancer were enrolled and received olaparib 400 mg twice a day. Patients were stratified according to whether they had aBRCA1orBRCA2mutation or not. The primary endpoint was objective response rate by Response Evaluation Criteria In Solid Tumors (RECIST). All patients who received treatment were included in the analysis of toxic effects, and patients who had measurable lesions at baseline were included in the primary efficacy analysis. This trial is registered atClinicalTrials.gov, numberNCT00679783. 91 patients were ...


  • PARP inhibitors in cancer: moving beyond BRCA
    The Lancet Oncology, sous presse, 2011 (commentaire en libre accès)
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    Mené sur 91 patientes, cet essai de phase II évalue l'olaparib pour le traitement d'un cancer ovarien de haut grade et/ou indifférencié ou d'un cancer du sein triple négatif de stade avancé

    “PARP inhibitors in cancer: moving beyond BRCA”

    • Telli, Melinda L.


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

Menées sur 3 patients atteints d'une leucémie lymphoïde chronique avancée, ces deux études évaluent une nouvelle immunothérapie antitumorale à base de lymphocytes T autologues génétiquement modifiés

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    Menées sur 3 patients atteints d'une leucémie lymphoïde chronique avancée, ces deux études évaluent une nouvelle immunothérapie antitumorale à base de lymphocytes T autologues génétiquement modifiés

    “T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia”

    • Kalos, Michael;Levine, Bruce L.;Porter, David L.;Katz, Sharyn;Grupp, Stephan A.;Bagg, Adam;June, Carl H.

    Tumor immunotherapy with T lymphocytes, which can recognize and destroy malignant cells, has been limited by the ability to isolate and expand T cells restricted to tumor-associated antigens. Chimeric antigen receptors (CARs) composed of antibody binding domains connected to domains that activate T cells could overcome tolerance by allowing T cells to respond to cell surface antigens; however, to date, lymphocytes engineered to express CARs have demonstrated minimal in vivo expansion and antitumor effects in clinical trials. We report that CAR T cells that target CD19 and contain a costimulatory domain from CD137 and the T cell receptor ζ chain have potent non–cross-resistant clinical activity after infusion in three of three patients treated with advanced chronic lymphocytic leukemia (CLL). The engineered T cells expanded >1000-fold in vivo, trafficked to bone marrow, and continued to express functional CARs at high levels for at least 6 months. Evidence for on-target toxicity ...


  • Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia
    New England Journal of Medicine, sous presse, 0 (article en libre accès)
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    Menées sur 3 patients atteints d'une leucémie lymphoïde chronique avancée, ces deux études évaluent une nouvelle immunothérapie antitumorale à base de lymphocytes T autologues génétiquement modifiés

    “Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia”

    • Porter, David L. ; Levine, Bruce L. ; Kalos, Michael ; Bagg, Adam ; June, Carl H.


  • Redirecting T Cells
    New England Journal of Medicine, sous presse, 0 (éditorial en libre accès)
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    Menées sur 3 patients atteints d'une leucémie lymphoïde chronique avancée, ces deux études évaluent une nouvelle immunothérapie antitumorale à base de lymphocytes T autologues génétiquement modifiés

    “Redirecting T Cells”

    • Urba, Walter J. ; Longo, Dan L.


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

Cette étude identifie le rôle joué par la phosphatase PPM1H dans l'apparition d'une résistance au trastuzumab chez les patientes atteintes d'un cancer du sein HER2+

  • PPM1H is a p27 phosphatase implicated in trastuzumab resistance
    Cancer Discovery, sous presse, 2011 (résumé)
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    Cette étude identifie le rôle joué par la phosphatase PPM1H dans l'apparition d'une résistance au trastuzumab chez les patientes atteintes d'un cancer du sein HER2+

    “PPM1H is a p27 phosphatase implicated in trastuzumab resistance”

    • Lee-Hoeflich, Si Tuen;Pham, Thinh Q.;Dowbenko, Don;Munroe, Xander;Lee, James;Li, Li;Zhou, Wei;Haverty, Peter M.;Pujara, Kanan;Stinson, Jeremy;Chan, Sara M.;Eastham-Anderson, Jeffery;Pandita, Ajay;Seshagiri, Somasekar;Hoeflich, Klaus P.;Turashvili, Gulisa;Gelmon, Karen A.;Aparicio, Samuel A.;Davis, David P.;Sliwkowski, Mark X.;Stern, Howard M.

    The HER2 oncogene is overexpressed or amplified in 20% of breast cancers. HER2-positive cancer historically portends a poor prognosis, but the HER2-targeted therapy trastuzumab mitigates this otherwise ominous distinction. Nevertheless, some patients suffer disease recurrence despite trastuzumab, and metastatic disease remains largely incurable due to innate and acquired resistance. Thus, understanding trastuzumab resistance remains an unmet medical need. Through RNAi screening, we discovered that knockdown of the serine/threonine phosphatase PPM1H confers trastuzumab resistance via reduction in protein levels of the tumour suppressor p27. PPM1H dephosphorylates p27 at threonine 187, thus removing a signal for proteasomal degradation. We further determined that patients whose tumours express low levels of PPM1H trend towards worse clinical outcome on trastuzumab. Identifying PPM1H as a novel p27 phosphatase reveals new insight into how cancer cells destabilize a well-recognized tumour ...


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

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

  • Cancer immunotherapy – revisited
    Nature Reviews Drug Discovery, Vol. 10 (8), pp. 591-600, 2011 (résumé)
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    Cet article passe en revue les travaux récents en immunothérapie des cancers

    “Cancer immunotherapy – revisited”

    • Lesterhuis, W. Joost;Haanen, John B. A. G.;Punt, Cornelis J. A.

    Our insight into antitumour immune responses has increased considerably during the past decades, yet the development of immunotherapy as a treatment modality for cancer has been hampered by several factors. These include difficulties in the selection of the optimal dose and schedule, the methods of evaluation, and financial support. Although durable clinical remissions have been observed with various immunotherapeutic strategies, the percentage of patients who benefited from these interventions has remained too small to justify the general use of such strategies. However, the recent positive results of clinical trials with novel immunoactive drugs as well as the unexpected finding of a positive interaction between immunotherapy and chemotherapy may herald a new era for the immunotherapy of cancer.


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

Cet article passe en revue les perspectives offertes par le ciblage de l'angiogenèse pour le traitement des cancers ovariens

  • Targeting angiogenesis in ovarian cancer
    Cancer treatment reviews, sous presse, 2011 (résumé)
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    Cet article passe en revue les perspectives offertes par le ciblage de l'angiogenèse pour le traitement des cancers ovariens

    “Targeting angiogenesis in ovarian cancer”

    • Schmitt, Jordan;Matei, Daniela

    Results of standard chemotherapy in ovarian cancer are hampered by the development of drug resistance leading to disease recurrence. This prompted interest in the development of therapies targeting critical pathways responsible for tumor progression. Angiogenesis is a key process that enables ovarian cancer growth and metastasis in the peritoneal space. Its regulation relies on signaling mechanisms initiated by the vascular endothelial growth factor, the platelet-derived growth factor, the fibroblast growth factor, angiopoietins, and others. These pathways are not only important to the modulation of the tumor microenvironment and vasculature, but also control cancer cell proliferation and survival. In this review, we discuss preclinical evidence supporting the rationale for inhibiting these pathways and provide an overview for the clinical development of agents targeting them. Clinical trials evaluating such agents alone and in combination with chemotherapy are ongoing. Early clinical ...


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

Traitements systémiques : applications cliniques

Menée sur 217 patientes, cette étude évalue le trastuzumab en complément d'une chimiothérapie néoadjuvante pour le traitement d'un cancer du sein HER2+

  • Chemotherapy, Trastuzumab, and Pathological Complete Response: When Shall We Three Meet Again?
    Journal of Clinical Oncology, sous presse, 2011 (éditorial en libre accès)
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    Menée sur 217 patientes, cette étude évalue le trastuzumab en complément d'une chimiothérapie néoadjuvante pour le traitement d'un cancer du sein HER2+

    “Chemotherapy, Trastuzumab, and Pathological Complete Response: When Shall We Three Meet Again?”

    • Cameron, David A.


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    Menée sur 217 patientes, cette étude évalue le trastuzumab en complément d'une chimiothérapie néoadjuvante pour le traitement d'un cancer du sein HER2+

    “Pathologic Complete Response After Neoadjuvant Chemotherapy Plus Trastuzumab Predicts Favorable Survival in Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer: Results From the TECHNO Trial of the AGO and GBG Study Groups”

    • Untch, Michael ; Fasching, Peter A. ; Konecny, Gottfried E. ; Hasmüller, Stephan ; Lebeau, Annette ; Kreienberg, Rolf ; Camara, Oumar ; Müller, Volkmar ; du Bois, Andreas ; Kühn, Thorsten ; Stickeler, Elmar ; Harbeck, Nadia ; Höss, Cornelia ; Kahlert, Steffen ; Beck, Thomas ; Fett, Werner ; Mehta, Keyur M. ; von Minckwitz, Gunter ; Loibl, Sibylle

    Purpose To evaluate efficacy and safety of epirubicin and cyclophosphamide followed by paclitaxel and trastuzumab as neoadjuvant treatment in patients with human epidermal growth factor receptor 2 (HER2)–overexpressing breast cancer.Patients and Methods Patients with centrally confirmed HER2-overexpressing breast cancer (≥ 2 cm or inflammatory) received four 3-week cycles epirubicin and cyclophosphamide (90/600 mg/m2) followed by four 3-week cycles paclitaxel (175 mg/m2) and trastuzumab (6 mg/kg) before surgery. Trastuzumab was continued after surgery to complete 1 year of treatment. Primary end point was pathologic complete response (pCR) defined as no residual invasive tumor in breast and lymphatic tissue.Results Thirty-nine percent of 217 enrolled patients achieved a pCR. Breast conservation was possible in 64% of patients. Three-year disease-free survival (DFS) was 88% in patients with pCR compared to 73% in patients without pCR (P = .01). Three-year overall survival (OS) was ...


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

Mené sur 331 patients atteints d'un lymphome hodgkinien, cet essai compare deux protocoles de chimiothérapie, BEACOPP et ABDV, suivis d'une radiothérapie locale si nécessaire (durée médiane de suivi : 61 mois)

  • Hodgkin's Lymphoma — The Great Teacher
    New England Journal of Medicine, Vol. 365 (3), pp. 264-265, 2011 (éditorial)
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    Mené sur 331 patients atteints d'un lymphome hodgkinien, cet essai compare deux protocoles de chimiothérapie, BEACOPP et ABDV, suivis d'une radiothérapie locale si nécessaire (durée médiane de suivi : 61 mois)

    “Hodgkin's Lymphoma — The Great Teacher”

    • Connors, Joseph M.


  • ABVD versus BEACOPP for Hodgkin's Lymphoma When High-Dose Salvage Is Planned
    New England Journal of Medicine, Vol. 365 (3), pp. 203-212, 2011 (résumé)
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    Mené sur 331 patients atteints d'un lymphome hodgkinien, cet essai compare deux protocoles de chimiothérapie, BEACOPP et ABDV, suivis d'une radiothérapie locale si nécessaire (durée médiane de suivi : 61 mois)

    “ABVD versus BEACOPP for Hodgkin's Lymphoma When High-Dose Salvage Is Planned”

    • Viviani, Simonetta ; Zinzani, Pier Luigi ; Rambaldi, Alessandro ; Brusamolino, Ercole ; Levis, Alessandro ; Bonfante, Valeria ; Vitolo, Umberto ; Pulsoni, Alessandro ; Liberati, Anna Marina ; Specchia, Giorgina ; Valagussa, Pinuccia ; Rossi, Andrea ; Zaja, Francesco ; Pogliani, Enrico M. ; Pregno, Patrizia ; Gotti, Manuel ; Gallamini, Andrea ; Scalabrini, Delia Rota ; Bonadonna, Gianni ; Gianni, Alessandro M.

    Background BEACOPP, an intensified regimen consisting of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, has been advocated as the new standard of treatment for advanced Hodgkin's lymphoma, in place of the combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Methods We randomly assigned 331 patients with previously untreated and unfavorable Hodgkin's lymphoma (stage IIB, III, or IV, or an international prognostic score of ≥3 on a scale of 0 to 7, with higher scores indicating increased risk), to receive either BEACOPP or ABVD, each followed by local radiotherapy when indicated. Patients with residual or progressive disease after the initial therapy were to be treated according to a state-of-the-art high-dose salvage program. The median follow-up period was 61 months. Results The 7-year rate of freedom from first progression was 85% among patients who had received initial treatment with BEACOPP and 73% among ...


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

Mené sur 846 patients atteints d'une leucémie myéloïde chronique Ph+, cet essai de phase III compare le nilotinib et l'imatinib en traitement de première ligne

  • First-line therapy for CML: nilotinib comes of age
    The Lancet Oncology, sous presse, 2011 (commentaire en libre accès)
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    Mené sur 846 patients atteints d'une leucémie myéloïde chronique Ph+, cet essai de phase III compare le nilotinib et l'imatinib en traitement de première ligne

    “First-line therapy for CML: nilotinib comes of age”

    • Davies, Jeff


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    Mené sur 846 patients atteints d'une leucémie myéloïde chronique Ph+, cet essai de phase III compare le nilotinib et l'imatinib en traitement de première ligne

    “Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial”

    • Kantarjian, Hagop M. ; Hochhaus, Andreas ; Saglio, Giuseppe ; Souza, Carmino De ; Flinn, Ian W. ; Stenke, Leif ; Goh, Yeow-Tee ; Rosti, Gianantonio ; Nakamae, Hirohisa ; Gallagher, Neil J. ; Hoenekopp, Albert ; Blakesley, Rick E. ; Larson, Richard A. ; Hughes, Timothy P.

    Nilotinib has shown greater efficacy than imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (CML) in chronic phase after a minimum follow-up of 12 months. We present data from the Evaluating Nilotinib Efficacy and Safety in clinical Trials?newly diagnosed patients (ENESTnd) study after a minimum follow-up of 24 months. ENESTnd was a phase 3, multicentre, open-label, randomised study. Adult patients were eligible if they had been diagnosed with chronic phase, Philadelphia chromosome-positive CML within the previous 6 months. Patients were randomly assigned (1:1:1) to receive nilotinib 300 mg twice a day, nilotinib 400 mg twice a day, or imatinib 400 mg once a day, all administered orally, by use of a computer-generated randomisation schedule, using permuted blocks, and stratified according to Sokal score. Efficacy results are reported for the intention-to-treat population. The primary endpoint was major molecular response at 12 months, ...


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

Menée sur 281 patientes italiennes atteintes d'un cancer du sein avant la ménopause, cet essai de phase III évalue l'efficacité de la triptoréline, un analogue de la gonadolibérine, pour prévenir une ménopause précoce induite par une chimiothérapie

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    Menée sur 281 patientes italiennes atteintes d'un cancer du sein avant la ménopause, cet essai de phase III évalue l'efficacité de la triptoréline, un analogue de la gonadolibérine, pour prévenir une ménopause précoce induite par une chimiothérapie

    “Effect of the Gonadotropin-Releasing Hormone Analogue Triptorelin on the Occurrence of Chemotherapy-Induced Early Menopause in Premenopausal Women With Breast Cancer”

    • Del Mastro, Lucia;Boni, Luca;Michelotti, Andrea;Gamucci, Teresa;Olmeo, Nina;Gori, Stefania;Giordano, Monica;Garrone, Ornella;Pronzato, Paolo;Bighin, Claudia;Levaggi, Alessia;Giraudi, Sara;Cresti, Nicola;Magnolfi, Emanuela;Scotto, Tiziana;Vecchio, Carlo;Venturini, Marco

    Context Premenopausal patients with breast cancer are at high risk of premature ovarian failure induced by systemic treatments, but no standard strategies for preventing this adverse effect are yet available.Objective To determine the effect of the temporary ovarian suppression obtained by administering the gonadotropin-releasing hormone analogue triptorelin during chemotherapy on the incidence of early menopause in young patients with breast cancer undergoing adjuvant or neoadjuvant chemotherapy.Design, Setting, and Patients The PROMISE-GIM6 (Prevention of Menopause Induced by Chemotherapy: A Study in Early Breast Cancer Patients–Gruppo Italiano Mammella 6) study, a parallel, randomized, open-label, phase 3 superiority trial, was conducted at 16 sites in Italy and enrolled 281 patients between October 2003 and January 2008. The patients were premenopausal women with stage I through III breast cancer who were candidates for adjuvant or neoadjuvant chemotherapy. Assuming a 60% rate ...


  • Reducing the Long-term Effects of Chemotherapy in Young Women With Early-Stage Breast Cancer
    JAMA: The Journal of the American Medical Association, Vol. 306 (3), pp. 312-314, 2011 (éditorial)
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    Menée sur 281 patientes italiennes atteintes d'un cancer du sein avant la ménopause, cet essai de phase III évalue l'efficacité de la triptoréline, un analogue de la gonadolibérine, pour prévenir une ménopause précoce induite par une chimiothérapie

    “Reducing the Long-term Effects of Chemotherapy in Young Women With Early-Stage Breast Cancer”

    • Rugo, Hope S. ; Rosen, Mitchell P.


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

Mené sur 165 patients chinois atteints d'un cancer avancé du poumon non à petites cellules présentant des mutations EGFR, cet essai de phase III compare l'erlotnib à une chimiothérapie combinant gemcitabine et carboplatine en traitement de première ligne

  • Erlotinib, gefitinib, or chemotherapy for EGFR mutation-positive lung cancer?
    The Lancet Oncology, Vol. 12 (8), pp. 710-711, 2011 (commentaire en libre accès)
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    Mené sur 165 patients chinois atteints d'un cancer avancé du poumon non à petites cellules présentant des mutations EGFR, cet essai de phase III compare l'erlotnib à une chimiothérapie combinant gemcitabine et carboplatine en traitement de première ligne

    “Erlotinib, gefitinib, or chemotherapy for EGFR mutation-positive lung cancer?”

    • Mitsudomi, Tetsuya


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    Mené sur 165 patients chinois atteints d'un cancer avancé du poumon non à petites cellules présentant des mutations EGFR, cet essai de phase III compare l'erlotnib à une chimiothérapie combinant gemcitabine et carboplatine en traitement de première ligne

    “Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study”

    • Zhou, Caicun ; Wu, Yi-Long ; Chen, Gongyan ; Feng, Jifeng ; Liu, Xiao-Qing ; Wang, Changli ; Zhang, Shucai ; Wang, Jie ; Zhou, Songwen ; Ren, Shengxiang ; Lu, Shun ; Zhang, Li ; Hu, Chengping ; Hu, Chunhong ; Luo, Yi ; Chen, Lei ; Ye, Ming ; Huang, Jianan ; Zhi, Xiuyi ; Zhang, Yiping ; Xiu, Qingyu ; Ma, Jun ; You, Changxuan

    Activating mutations inEGFRare important markers of response to tyrosine kinase inhibitor (TKI) therapy in non-small-cell lung cancer (NSCLC). The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus standard chemotherapy in the first-line treatment of patients with advancedEGFRmutation-positive NSCLC. We undertook an open-label, randomised, phase 3 trial at 22 centres in China. Patients older than 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation ofEGFR(exon 19 deletion or exon 21 L858R point mutation) received either oral erlotinib (150 mg/day) until disease progression or unacceptable toxic effects, or up to four cycles of gemcitabine plus carboplatin. Patients were randomly assigned (1:1) with a minimisation procedure and were stratified according toEGFRmutation type, histological subtype (adenocarcinomavsnon-adenocarcinoma), and smoking status. The primary outcome was progression-free survival, analysed in ...


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

A partir de données portant sur 932 patients ayant reçu une chimiothérapie à base de cisplatine, cette étude rétrospective met en évidence une incidence élevée d'événements thromboemboliques indésirables

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    A partir de données portant sur 932 patients ayant reçu une chimiothérapie à base de cisplatine, cette étude rétrospective met en évidence une incidence élevée d'événements thromboemboliques indésirables

    “High Incidence of Thromboembolic Events in Patients Treated With Cisplatin-Based Chemotherapy: A Large Retrospective Analysis”

    • Moore, Russell A.;Adel, Nelly;Riedel, Elyn;Bhutani, Manisha;Feldman, Darren R.;Tabbara, Nour Elise;Soff, Gerald;Parameswaran, Rekha;Hassoun, Hani

    Purpose This study was designed to determine the incidence of venous and arterial thromboembolic events (TEEs) in patients treated with cisplatin-based chemotherapy and to analyze the prognostic value of patients’ baseline and treatment characteristics in predicting TEE occurrence.Patients and Methods We performed a large retrospective analysis of all patients treated with cisplatin-based chemotherapy for any type of malignancy at Memorial Sloan-Kettering Cancer Center in 2008. A TEE was cisplatin-associated if it occurred between the time of the first dose of cisplatin and 4 weeks after the last dose.Results Among 932 patients, 169 (18.1%) experienced a TEE during treatment or within 4 weeks of the last dose. TEEs included deep vein thrombosis (DVT) alone in 49.7%, pulmonary embolus (PE) alone in 25.4%, DVT plus PE in 13.6%, arterial TEE alone in 8.3%, or DVT plus arterial TEE in 3.0%. TEEs occurred within 100 days of initiation of treatment in 88% of patients. By univariate ...


Mots clés : Traitements (Traitements systémiques : applications cliniques)

Mené sur 774 patients atteints d'un cancer gastrique avancé, cet essai de phase III évalue l'ajout de bevacizumab à une chimiothérapie combinant capécitabine et cisplatine en traitement de première ligne

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    Mené sur 774 patients atteints d'un cancer gastrique avancé, cet essai de phase III évalue l'ajout de bevacizumab à une chimiothérapie combinant capécitabine et cisplatine en traitement de première ligne

    “Bevacizumab in Combination With Chemotherapy As First-Line Therapy in Advanced Gastric Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase III Study”

    • Ohtsu, Atsushi;Shah, Manish A.;Van Cutsem, Eric;Rha, Sun Young;Sawaki, Akira;Park, Sook Ryun;Lim, Ho Yeong;Yamada, Yasuhide;Wu, Jian;Langer, Bernd;Starnawski, Michal;Kang, Yoon-Koo

    Purpose The Avastin in Gastric Cancer (AVAGAST) trial was a multinational, randomized, placebo-controlled trial designed to evaluate the efficacy of adding bevacizumab to capecitabine-cisplatin in the first-line treatment of advanced gastric cancer.Patients and Methods Patients received bevacizumab 7.5 mg/kg or placebo followed by cisplatin 80 mg/m2 on day 1 plus capecitabine 1,000 mg/m2 twice daily for 14 days every 3 weeks. Fluorouracil was permitted in patients unable to take oral medications. Cisplatin was given for six cycles; capecitabine and bevacizumab were administered until disease progression or unacceptable toxicity. The primary end point was overall survival (OS). Log-rank test was used to test the OS difference.Results In all, 774 patients were enrolled; 387 were assigned to each treatment group (intention-to-treat population), and 517 deaths were observed. Median OS was 12.1 months with bevacizumab plus fluoropyrimidine-cisplatin and 10.1 months with placebo plus ...


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

Mené par l'Intergroupe Francophone d'Oncologie Thoracique sur 451 patients d'âge compris entre 70 et 89 ans, cet essai de phase IIII évalue une chimiothérapie combinant carboplatine et paclitaxel pour le traitement d'un cancer du poumon non à petites cellules de stade avancé

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    Mené par l'Intergroupe Francophone d'Oncologie Thoracique sur 451 patients d'âge compris entre 70 et 89 ans, cet essai de phase IIII évalue une chimiothérapie combinant carboplatine et paclitaxel pour le traitement d'un cancer du poumon non à petites cellules de stade avancé

    “Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial”

    • Quoix, Elisabeth;Zalcman, Gérard;Oster, Jean-Philippe;Westeel, Virginie;Pichon, Eric;Lavolé, Armelle;Dauba, Jérôme;Debieuvre, Didier;Souquet, Pierre-Jean;Bigay-Game, Laurence;Dansin, Eric;Poudenx, Michel;Molinier, Olivier;Vaylet, Fabien;Moro-Sibilot, Denis;Herman, Dominique;Bennouna, Jaafar;Tredaniel, Jean;Ducoloné, Alain;Lebitasy, Marie-Paule;Baudrin, Laurence;Laporte, Silvy;Milleron, Bernard

    Platinum-based doublet chemotherapy is recommended to treat advanced non-small-cell lung cancer (NSCLC) in fit, non-elderly adults, but monotherapy is recommended for patients older than 70 years. We compared a carboplatin and paclitaxel doublet chemotherapy regimen with monotherapy in elderly patients with advanced NSCLC. In this multicentre, open-label, phase 3, randomised trial we recruited patients aged 70?89 years with locally advanced or metastatic NSCLC and WHO performance status scores of 0?2. Patients received either four cycles (3 weeks on treatment, 1 week off treatment) of carboplatin (on day 1) plus paclitaxel (on days 1, 8, and 15) or five cycles (2 weeks on treatment, 1 week off treatment) of vinorelbine or gemcitabine monotherapy. Randomisation was done centrally with the minimisation method. The primary endpoint was overall survival, and analysis was done by intention to treat. This trial is registered, numberNCT00298415. 451 patients were enrolled. 226 were randomly ...


  • Détails
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    Mené par l'Intergroupe Francophone d'Oncologie Thoracique sur 451 patients d'âge compris entre 70 et 89 ans, cet essai de phase IIII évalue une chimiothérapie combinant carboplatine et paclitaxel pour le traitement d'un cancer du poumon non à petites cellules de stade avancé

    “Combination chemotherapy for older adults with advanced non-small-cell lung cancer”

    • Reckamp, Karen L.


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

Menée auprès de 1 526 patients atteints d'un cancer colorectal et recevant une chimiothérapie avec ou sans thérapie ciblée supplémentaire, cette étude évalue l'impact de l'indice de masse corporelle sur leur survie

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    Menée auprès de 1 526 patients atteints d'un cancer colorectal et recevant une chimiothérapie avec ou sans thérapie ciblée supplémentaire, cette étude évalue l'impact de l'indice de masse corporelle sur leur survie

    “Influence of body mass index on outcome in advanced colorectal cancer patients receiving chemotherapy with or without targeted therapy”

    • Simkens, Lieke H. J.;Koopman, Miriam;Mol, Linda;Veldhuis, Gerrit Jan;Ten Bokkel Huinink, Daan;Muller, Erik W.;Derleyn, Veerle A.;Teerenstra, Steven;Punt, Cornelis J. A.

    Obesity is associated with an increased risk of development and recurrence of colorectal cancer. However, the role of obesity in advanced colorectal cancer (ACC) patients is unknown. We investigated the effect of body mass index (BMI) on overall survival (OS) in ACC patients receiving systemic treatment in two large phase III studies (CAIRO and CAIRO2). Treatment data were obtained and analysed from 796 ACC patients who were treated with chemotherapy in the CAIRO study, and from 730 ACC patients who were treated with chemotherapy plus targeted therapy in the CAIRO2 study. Baseline height and weight were used to assign patients to one of the following BMI categories: A (<18.5kg/m2), B (18.5–24.9kg/m2), C (25.0–29.9kg/m2) and D (⩾30.0kg/m2). In 796 patients of the CAIRO study a high BMI was associated with better median OS (8.0, 14.9, 18.4 and 19.5months for BMI categories A, B, C, and D, respectively; P=0.001), and was an independent prognostic factor for OS in a multivariate ...


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

Ressources et infrastructures (Traitements)

Cet article passe en revue les enjeux actuels des essais cliniques dans les cancers du poumon non à petites cellules

  • Problems involved in the clinical trials for non-small cell lung carcinoma
    Cancer treatment reviews, sous presse, 2011 (résumé)
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    Cet article passe en revue les enjeux actuels des essais cliniques dans les cancers du poumon non à petites cellules

    “Problems involved in the clinical trials for non-small cell lung carcinoma”

    • Saijo, Nagahiro

    Along with changes in smoking habits, non-small cell lung carcinoma (NSCLC) has come to account for about 90% of all cases of lung cancer. For the treatment of NSCLC, cytocidal antineoplastic drugs such as pemetrexed and molecular-targeted drugs such as gefitinib, erlotinib, and bevacizumab have been approved globally and used as a part of the standard treatment. The importance of better patient selection based on the optimum indication of these drugs is attracting much attention. Additionally, timing for the use of these drugs also seems to be an important issue. The present review presents a critical discussion about the following issues based on the results of clinical studies: (1) whether or not the assessment of the EGFR mutation status in NSCLC patients is indispensable; (2) whether gefitinib and erlotinib have different effects; (3) the need to sub-classify NSCLC by histologic type; (4) significance of maintenance therapy for NSCLC; and (5) whether platinum-doublet chemotherapy ...


Mots clés : Poumon; Traitements (Ressources et infrastructures (Traitements))

Cet article plaide pour l'inclusion de patients atteints de tumeurs cérébrales dans des essais de phase I en oncologie

  • It Is Time to Include Patients With Brain Tumors in Phase I Trials in Oncology
    Journal of Clinical Oncology, Vol. 29 (24), pp. 3211-3213, 2011 (article en libre accès)
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    Cet article plaide pour l'inclusion de patients atteints de tumeurs cérébrales dans des essais de phase I en oncologie

    “It Is Time to Include Patients With Brain Tumors in Phase I Trials in Oncology”

    • Wen, Patrick Y.;Schiff, David;Cloughesy, Timothy F.;Reardon, David A.;Batchelor, Tracy T.;Chabner, Flaherty, Bruce A., Keith;de Groot, Gilbert, John F., Mark R.;Galanis, Evanthia;Chang, Susan M.;Schwartz, Gary K.;Peereboom, David;Mehta, Minesh P.;Yung, W.K. Alfred;Grossman, Stuart A.;Prados, Michael D.;DeAngelis, Lisa M.


Mots clés : Système nerveux central; Traitements (Ressources et infrastructures (Traitements))

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