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Accueil Nota Bene Cancer V2 Numéro 131 du 11 Avril 2012 Traitements

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Nota Bene Cancer Numéro 131 du 11 Avril 2012 RSS

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Traitements localisés : applications cliniques

A partir des données portant sur 15 369 patientes atteintes d'un cancer du sein de stade précoce, cette étude évalue l'évolution du taux de mastectomie en Europe sur la période 2005 - 2010

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    A partir des données portant sur 15 369 patientes atteintes d'un cancer du sein de stade précoce, cette étude évalue l'évolution du taux de mastectomie en Europe sur la période 2005 - 2010

    “Mastectomy trends for early-stage breast cancer: A report from the EUSOMA multi-institutional European database”

    • Garcia-Etienne, Carlos A.;Tomatis, Mariano;Heil, Joerg;Friedrichs, Kay;Kreienberg, Rolf;Denk, Andreas;Kiechle, Marion;Lorenz-Salehi, Fatemeh;Kimmig, Rainer;Emons, Günter;Danaei, Mahmoud;Heyl, Volker;Heindrichs, Uwe;Rageth, Christoph J.;Janni, Wolfgang;Marotti, Lorenza;Turco, Marco Rosselli del;Ponti, Antonio

    Introduction Recent single-institution reports have shown increased mastectomy rates during the last decade. Further studies aiming to determine if these reports could be reflecting a national trend in the United States of America (US) have shown conflicting results. We report these trends from a multi-institutional European database. Patients and methods Our source of data was the eusomaDB, a central data warehouse of prospectively collected information of the European Society of Breast Cancer Specialists (EUSOMA). We identified patients with newly diagnosed unilateral early-stage breast cancer (stages 0, I or II) to examine rates and trends in surgical treatment. Results A total of 15,369 early-stage breast cancer cases underwent surgery in 13 Breast Units from 2003 to 2010. Breast conservation was successful in 11,263 cases (73.3%). Adjusted trend by year showed a statistically significant decrease in mastectomy rates from 2005 to 2010 (p = 0.003) with a progressive ...


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

Menée à partir de données des registres américains du cancer incluant 52 249 patientes atteintes d'un cancer canalaire et/ou lobulaire du sein diagnostiqué entre 1998 et 2002, cette étude évalue, du point de vue de la survie spécifique, les résultats cliniques d'une mastectomie en combinaison avec une reconstruction mammaire réalisée pendant ou peu après l'opération

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    Menée à partir de données des registres américains du cancer incluant 52 249 patientes atteintes d'un cancer canalaire et/ou lobulaire du sein diagnostiqué entre 1998 et 2002, cette étude évalue, du point de vue de la survie spécifique, les résultats cliniques d'une mastectomie en combinaison avec une reconstruction mammaire réalisée pendant ou peu après l'opération

    “A Population-Based Study of Breast Cancer-Specific Survival Following Mastectomy and Immediate or Early-Delayed Breast Reconstruction”

    • Agarwal, Jayant;Agarwal, Shailesh;Pappas, Lisa;Neumayer, Leigh

    Abstract: Immediate breast reconstruction allows for improved patient psychosocial outcomes after mastectomy. We used the Surveillance, Epidemiology, and End Results (SEER) database to study the breast cancer-specific survival of patients treated with immediate or early-delayed breast reconstruction after mastectomy. Population-level de-identified data was abstracted from the SEER database. All female patients treated with mastectomy for a diagnosis of ductal and/or lobular breast cancer between 1998 and 2002 were included. Breast cancer-specific survival was reported as hazard ratios using multivariate analysis to control for patient demographic and oncologic covariates. Demographic covariates included age, race, marital status, income, education, and county metropolitan status; oncologic covariates included tumor stage, histology, grade, lymph node status, hormone receptor status, receipt of radiation therapy, and unilateral or bilateral mastectomy. A total of 52,249 patients were ...


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

A partir de données portant sur 263 707 patients atteints d'un cancer du rein entre 1998 et 2008, cette étude compare les événements indésirables péri-opératoires associés à deux techniques de néphrectomie radicale, l'une par voie ouverte et l'autre par laparoscopie

  • Inpatient safety trends in laparoscopic and open nephrectomy for renal tumours
    BJU International, sous presse, 2012 (résumé)
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    A partir de données portant sur 263 707 patients atteints d'un cancer du rein entre 1998 et 2008, cette étude compare les événements indésirables péri-opératoires associés à deux techniques de néphrectomie radicale, l'une par voie ouverte et l'autre par laparoscopie

    “Inpatient safety trends in laparoscopic and open nephrectomy for renal tumours”

    • Stroup, Sean P.;Palazzi, Kerrin L.;Chang, David C.;Ward, Nicholas T.;Parsons, J. Kellogg

    Study Type – Cohort studyLevel of Evidence 2bWhat's known on the subject? and What does the study add?Laparoscopic radical nephrectomy for renal cancer provides equivalent long-term cancer control with shorter hospital stays, less postoperative pain, and faster resumption of normal activities, but it has diffused slowly into clinical practice, perhaps as a result of perceptions about safety. Patient safety outcomes for laparoscopic and open radical nephrectomy using validated measures remain incompletely characterized.This is the first study to investigate peri-operative outcomes of radical nephrectomy using validated patient safety measures. We found a 32% decreased probability of adverse patient safety events occurring in laparoscopic compared with open radical nephrectomy. The safety benefits of laparoscopy were attained only after 10% of cases were completed laparoscopically – a proportion some have proposed as the ‘tipping point’ for the adoption of surgical innovations. ...


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

A partir des données d'un registre canadien du cancer, cette étude compare les résultats cliniques d'une prostatectomie radicale et d'une radiothérapie chez les patients atteints d'un cancer de la prostate non métastatique et présentant un niveau très élevé de l'antigène prostatique spécifique (8 378 cas ; durée médiane de suivi : 67, 2 mois)

  • Treatment Outcomes in Non-Metastatic Prostate Cancer Patients With Ultra-High Prostate-Specific Antigen
    International journal of radiation oncology, biology, physics, sous presse, 2012 (résumé)
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    A partir des données d'un registre canadien du cancer, cette étude compare les résultats cliniques d'une prostatectomie radicale et d'une radiothérapie chez les patients atteints d'un cancer de la prostate non métastatique et présentant un niveau très élevé de l'antigène prostatique spécifique (8 378 cas ; durée médiane de suivi : 67, 2 mois)

    “Treatment Outcomes in Non-Metastatic Prostate Cancer Patients With Ultra-High Prostate-Specific Antigen”

    • Tai, Patricia;Tonita, Jon;Woitas, Carla;Zhu, Tong;Joseph, Kurian;Skarsgard, David

    It is commonly believed that prostate cancer patients with very high prostate-specific antigen (PSA) levels are unlikely to benefit from definitive local treatment, and patients with very high PSA are often underrepresented in, or excluded from, randomized clinical trials. Consequently, little is known about their optimal treatment or prognosis. We performed a registry-based analysis of management and outcome in this population of patients. Our provincial Cancer Registry was used to identify all men who were diagnosed with prostate cancer from 1990 to 2001. A retrospective chart review provided information on stage, Gleason score, PSA at diagnosis, and treatment. In this study, ultra-high PSA was defined as PSA of ≥50 ng/ml. For a more complete perspective, treatment outcomes of patients with PSA of 20 to 49.9 ng/ml were also studied. Of the 8378 men diagnosed with prostate cancer during this period, 6,449 had no known nodal or distant metastatic disease. The median follow-up of ...


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

Cette étude montre l'efficacité d'une prostatectomie radicale pour traiter un cancer localisé de la prostate associé à un score de Gleason supérieur ou égal à 8 (580 cas ; âge : 41 à 85 ans ; durée moyenne de suivi : 53 mois)

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    Cette étude montre l'efficacité d'une prostatectomie radicale pour traiter un cancer localisé de la prostate associé à un score de Gleason supérieur ou égal à 8 (580 cas ; âge : 41 à 85 ans ; durée moyenne de suivi : 53 mois)

    “Radical prostatectomy represents an effective treatment in patients with specimen-confined high pathological Gleason score prostate cancer”

    • Lughezzani, Giovanni;Gallina, Andrea;Larcher, Alessandro;Briganti, Alberto;Capitanio, Umberto;Suardi, Nazareno;Lista, Giuliana;Abrate, Alberto;Sangalli, Mattia Nicola;Buffi, Nicolòmaria;Cestari, Andrea;Guazzoni, Giorgio;Rigatti, Patrizio;Montorsi, Francesco

    Study Type – Prognosis (individual cohort)Level of Evidence 2bWhat's known on the subject? and What does the study add?To date, only a few studies have addressed the long-term oncological outcomes of radical prostatectomy (RP) in patients with pathological Gleason score ≥ 8 prostate cancer. According to these reports, some individuals with pathological Gleason score ≥ 8 may benefit from RP, with cancer-control outcomes comparable with those of patients with low- and intermediate-risk prostate cancer.The presence of pathological Gleason score 8–10 represents a poor prognostic factor in the outcome of men with prostate cancer. However, in patients with specimen-confined disease, RP and bilateral PLND provided long-term cancer-control outcomes similar to those of patients with more favourable disease characteristics. OBJECTIVES * •To evaluate the outcomes of patients with pathological Gleason score 8–10 prostate cancer subjected to radical prostatectomy (RP). * •To ...


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

A partir des données d'un registre japonais portant sur 436 patients atteints d'un cancer du poumon non à petites cellules de stade IIIA-cN2/pN2 et traités par chirurgie en 2004 (332 hommes, 104 femmes ; âge moyen : 65 ans), cette étude évalue la survie à 5 ans

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    A partir des données d'un registre japonais portant sur 436 patients atteints d'un cancer du poumon non à petites cellules de stade IIIA-cN2/pN2 et traités par chirurgie en 2004 (332 hommes, 104 femmes ; âge moyen : 65 ans), cette étude évalue la survie à 5 ans

    “Surgical Outcome of Stage IIIA- cN2/pN2 Non-Small-Cell Lung Cancer Patients in Japanese Lung Cancer Registry Study in 2004”

    • Yoshino, Ichiro;Yoshida, Shigetoshi;Miyaoka, Etsuo;Asamura, Hisao;Nomori, Hiroaki;Fujii, Yoshitaka;Nakanishi, Yoichi;Eguchi, Kenji;Mori, Masaki;Sawabata, Noriyoshi;Okumura, Meinoshin;Yokoi, Kohei;for the Japanese Joint Committee of Lung Cancer Registration

    Background: The role of surgery in the treatment of non-small-cell lung cancer (NSCLC ) with clinically manifested mediastinal node metastasis is controversial even in resectable cases because it is often accompanied by systemic micrometastasis. However, surgery is occasionally indicated for cases with single-station N2 disease or within multimodal treatment regimens, and in clinical trials. The aim of this study is to evaluate surgical outcomes in a modern cohort of patients with clinical (c-) stage IIIA -N2 NSCLC whose nodal metastasis was confirmed by pathology (cN2/pN2). Methods: From the central database of lung cancer patients undergoing surgery in 2004, which was founded by the Japanese Joint Committee for Lung Cancer Registration, data of patients having all conditions of NSCLC , c-stage IIIA , cN2, and pN2 were extracted, and the clinicopathologic profile of patients and surgical outcomes were evaluated. Results: Among 11,663 registered NSCLC cases, 436 patients (3.8%) (332 ...


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

Traitements systémiques : découverte et développement

Mené sur 272 patients atteints d'un carcinome à cellules rénales de stade avancé ou métastatique, cet essai de phase II évalue le tivozanib, un inhibiteur de trois récepteurs du facteur de croissance de l'endothélium vasculaire

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    Mené sur 272 patients atteints d'un carcinome à cellules rénales de stade avancé ou métastatique, cet essai de phase II évalue le tivozanib, un inhibiteur de trois récepteurs du facteur de croissance de l'endothélium vasculaire

    “Antitumor Activity and Safety of Tivozanib (AV-951) in a Phase II Randomized Discontinuation Trial in Patients With Renal Cell Carcinoma”

    • Nosov, Dmitry A.;Esteves, Brooke;Lipatov, Oleg N.;Lyulko, Alexei A.;Anischenko, A. A.;Chacko, Raju T.;Doval, Dinesh C.;Strahs, Andrew;Slichenmyer, William J.;Bhargava, Pankaj

    Purpose The antitumor activity and safety of tivozanib, which is a potent and selective vascular endothelial growth factor receptor-1, -2, and -3 inhibitor, was assessed in patients with advanced/metastatic renal cell carcinoma (RCC).Patients and Methods In this phase II, randomized discontinuation trial, 272 patients received open-label tivozanib 1.5 mg/d (one cycle equaled three treatment weeks followed by a 1-week break) orally for 16 weeks. Thereafter, 78 patients who demonstrated ≥ 25% tumor shrinkage continued to take tivozanib, and 118 patients with less than 25% tumor change were randomly assigned to receive tivozanib or a placebo in a double-blind manner; patients with ≥ 25% tumor growth were discontinued. Primary end points included safety, the objective response rate (ORR) at 16 weeks, and the percentage of randomly assigned patients who remained progression free after 12 weeks of double-blind treatment; secondary end points included progression-free survival ...


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

Menée sur 5 patientes atteintes d'un cancer ovarien de haut grade résistant aux sels de platine, cette étude évalue l'intérêt du trientine, un chélateur du cuivre, pour restaurer la sensibilité des tumeurs aux sels de platine

  • Overcoming Platinum Resistance Through the Use of a Copper-Lowering Agent
    Molecular Cancer Therapeutics, sous presse, 2012 (résumé)
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    Menée sur 5 patientes atteintes d'un cancer ovarien de haut grade résistant aux sels de platine, cette étude évalue l'intérêt du trientine, un chélateur du cuivre, pour restaurer la sensibilité des tumeurs aux sels de platine

    “Overcoming Platinum Resistance Through the Use of a Copper-Lowering Agent”

    • Fu, Siqing;Naing, Aung;Fu, Caroline;Kuo, Macus Tien;Kurzrock, Razelle

    Low levels of human copper transporter 1 (hCtr1) mRNA are associated with a shorter progression-free survival after platinum-based therapy. Pretreatment with a copper-lowering agent such as trientine enhanced hCtr1-mediated platinum uptake. Therefore, we conducted a pilot study (NCT01178112) of carboplatin and trientine with the goal of resensitizing advanced cancer patients to platinum chemotherapy. This case report reviews the outcomes of five patients with platinum-resistant high-grade epithelial ovarian cancer enrolled on the study to date. Overall, they tolerated treatment well. Severe adverse events that occurred in two patients were myelosuppression, notably anemia requiring transfusion. Dose-limiting toxicity was not observed within the first 28 days (cycle 1). After two cycles of therapy, partial remission was achieved in one patient (10+ months), stable disease in three patients (2, 3.5+ and 5 months, respectively), and one patient had progressive disease. These cases ...


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

Menée sur des lignées cellulaires, à l'aide de xénogreffes et d'échantilllons prélevés sur des patients atteints de myélome multiple, cette étude met en évidence une activité antitumorale de la combinaison d'agonistes du récepteur A2A et du récepteur bêta-2-adrénergique

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    Menée sur des lignées cellulaires, à l'aide de xénogreffes et d'échantilllons prélevés sur des patients atteints de myélome multiple, cette étude met en évidence une activité antitumorale de la combinaison d'agonistes du récepteur A2A et du récepteur bêta-2-adrénergique

    “Adenosine A2A and Beta-2 Adrenergic Receptor Agonists: Novel Selective and Synergistic Multiple Myeloma Targets Discovered through Systematic Combination Screening”

    • Rickles, Richard J.;Tam, Winnie F;Giordano, Thomas P;Pierce, Laura T;Farwell, Melissa;McMillin, Douglas W.;Necheva, Antoaneta;Crowe, David;Chen, Mei;Avery, William;Kansra, Vikram;Nawrocki, Steffan T;Carew, Jennifer S;Giles, Francis;Mitsiades, Constantine S.;Borisy, Alexis A;Anderson, Kenneth C.;Lee, Margaret S

    The use of combination drug regimens has dramatically improved the clinical outcome for multiple myeloma (MM) patients. However, to date, combination treatments have been limited to approved drugs and a small number of emerging agents. Using a systematic approach to identify synergistic drug combinations, combination high throughput screening (cHTS) technology, adenosine A2A and beta-2 adrenergic receptor agonists were shown to be highly synergistic, selective and novel agents that enhance glucocorticoid activity in B-cell malignancies. Unexpectedly, A2A and beta-2 adrenergic receptor agonists also synergize with melphalan, lenalidomide, bortezomib and doxorubicin. An analysis of agonists in combination with dexamethasone (Dex) or melphalan in 83 cell lines reveals substantial activity in MM and diffuse large B cell lymphoma cell lines. Combination effects are also observed with Dex as well as bortezomib, using MM patient samples and mouse MM xenograft assays. Our results provide ...


Mots clés : Myélome multiple et maladies immunoprolifératives; Traitements (Traitements systémiques : découverte et développement)

Menée sur un modèle murin, cette étude suggère que l'inhibition de la bêta-caténine, en combinaison avec l'imatinib, a un effet sur les cellules souches de leucémie myéloïde chronique

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    Menée sur un modèle murin, cette étude suggère que l'inhibition de la bêta-caténine, en combinaison avec l'imatinib, a un effet sur les cellules souches de leucémie myéloïde chronique

    “Genetic and Pharmacologic Inhibition of Beta-Catenin Targets Imatinib-Resistant Leukemia Stem Cells in CML”

    • Heidel, Florian H;Bullinger, Lars;Feng, Zhaohui;Wang, Zhu;Neff, Tobias A;Stein, Lauren;Kalaitzidis, Demetrios;Lane, Steven W;Armstrong, Scott A

    A key characteristic of hematopoietic stem cells (HSCs) is the ability to self-renew. Genetic deletion of β -catenin during fetal HSC development leads to impairment of self-renewal while β -catenin is dispensable in fully developed adult HSCs. Whether β -catenin is required for maintenance of fully developed CML leukemia stem cells (LSCs) is unknown. Here, we use a conditional mouse model to show that deletion of β -catenin after CML initiation does not lead to a significant increase in survival. However, deletion of β -catenin synergizes with imatinib (IM) to delay disease recurrence after imatinib discontinuation and to abrogate CML stem cells. These effects can be mimicked by pharmacologic inhibition of β -catenin via modulation of prostaglandin signaling. Treatment with the cyclooxygenase inhibitor indomethacin reduces β -catenin levels and leads to a reduction in LSCs. In conclusion, inhibiting β -catenin by genetic inactivation or pharmacologic modulation is an ...


  • Targeting beta-catenin in CML: Leukemia Stem Cells Beware!
    Cell stem cell, Vol. 10 (4), pp. 351-353, 2012 (commentaire)
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    Menée sur un modèle murin, cette étude suggère que l'inhibition de la bêta-caténine, en combinaison avec l'imatinib, a un effet sur les cellules souches de leucémie myéloïde chronique

    “Targeting beta-catenin in CML: Leukemia Stem Cells Beware!”

    • Kleppe, Maria ; Levine, Ross L

    In this issue of Cell Stem Cell, Heidel et al. (2012) use genetic and pharmacological approaches to reveal that Wnt/²-catenin signaling is required for leukemic stem cell (LSC) maintenance in chronic myeloid leukemia. They demonstrate that ²-catenin inactivation targets imanitib-resistant LSCs in vivo.


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

Cet article passe en revue les mécanismes de résistance thérapeutique associée à une hétérogénéité clonale des tumeurs et identifie des approches cliniques pour prendre en compte cette hétérogénéité

  • Genetic heterogeneity and cancer drug resistance
    The Lancet Oncology, Vol. 13 (4), pp. e178-e185, 2012 (résumé)
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    Cet article passe en revue les mécanismes de résistance thérapeutique associée à une hétérogénéité clonale des tumeurs et identifie des approches cliniques pour prendre en compte cette hétérogénéité

    “Genetic heterogeneity and cancer drug resistance”

    • Turner, Nicholas C.;Reis-Filho, Jorge S.

    Despite the success of targeted therapies in the treatment of cancer, the development of resistance limits the ability to translate this method into a curative treatment. The mechanisms of resistance have traditionally been thought of as intrinsic (ie, present at baseline) or acquired (ie, developed after initial response). Recent evidence has challenged the notion of acquired resistance. Although cancers are traditionally thought to be clonal, there is now evidence of intra-tumour genetic heterogeneity in most cancers. The clinical pattern of acquired resistance in many circumstances represents outgrowth of resistant clones that might have originally been present in the primary cancer at low frequency but that have expanded under the selective pressure imposed by targeted therapies. Here, we describe the potential role of clonal heterogeneity in resistance to targeted therapy, discuss genetic instability as one of its causes, and detail approaches to tackle intra-tumour heterogeneity ...


  • Biology-driven medicine: tissue matters
    The Lancet Oncology, Vol. 13 (4), pp. 319, 2012 (éditorial en libre accès)
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    Cet article passe en revue les mécanismes de résistance thérapeutique associée à une hétérogénéité clonale des tumeurs et identifie des approches cliniques pour prendre en compte cette hétérogénéité

    “Biology-driven medicine: tissue matters”

    • The Lancet, Oncology


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

Menée sur un modèle murin, cette étude suggère que la chimiokine Mig est un acteur majeur du mécanisme de toxicité létale consécutive à une chimiothérapie 5-FU

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    Menée sur un modèle murin, cette étude suggère que la chimiokine Mig est un acteur majeur du mécanisme de toxicité létale consécutive à une chimiothérapie 5-FU

    “Activated expression of the chemokine Mig following chemotherapy contributes to chemotherapy-induced bone marrow suppression and lethal toxicity”

    • Lu, Huili;Zhu, Shunying;Qian, Lan;Xiang, Di;Zhang, Wu;Nie, Aifang;Gao, Jin;Wu, Mingyuan;Gao, Jinming;Lu, Bao;Yu, Yan;Han, Wei;Moldenhauer, Anja

    Alterations in gene expression after chemotherapy may potentially help to identify mediators that induce suppression or regeneration in bone marrow. This paper reports our observation that the expression of the chemokine Mig (monokine induced by interferon γ) and its receptor CXCR3 was significantly activated in mice following treatment with the chemotherapeutic agent 5-fluorouracil (5-FU). The neutralization of antibodies against the activated Mig increased the survival rate and accelerated BM recovery after chemotherapy. In addition, elevation of Mig plasma levels post 5-FU treatment corresponded with increased mortality. The cell cycle-inhibiting effect of the prophylactic administration of Mig protected hematopoietic progenitor cells (HPC) from Ara-C in CFU-spleen assays and enhanced the irradiated recipients' survival. In CXCR3-/- mice, Mig did not propagate BM suppression, indicating that the suppressive effect of Mig is dependent on CXCR3. On the one hand, Mig stimulated p70 ...


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

Menée sur divers modèles animaux et des patients atteints de tumeurs solides avancées, cette étude analyse les caractéristiques pharmacologiques et pharmacocinétiques d'une nanoparticule contenant du docétaxel

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    Menée sur divers modèles animaux et des patients atteints de tumeurs solides avancées, cette étude analyse les caractéristiques pharmacologiques et pharmacocinétiques d'une nanoparticule contenant du docétaxel

    “Preclinical Development and Clinical Translation of a PSMA-Targeted Docetaxel Nanoparticle with a Differentiated Pharmacological Profile”

    • Hrkach, Jeffrey;Von Hoff, Daniel;Ali, Mir Mukkaram;Andrianova, Elizaveta;Auer, Jason;Campbell, Tarikh;De Witt, David;Figa, Michael;Figueiredo, Maria;Horhota, Allen;Low, Susan;McDonnell, Kevin;Peeke, Erick;Retnarajan, Beadle;Sabnis, Abhimanyu;Schnipper, Edward;Song, Jeffrey J.;Song, Young Ho;Summa, Jason;Tompsett, Douglas;Troiano, Greg;Van Geen Hoven, Tina;Wright, Jim;LoRusso, Patricia;Kantoff, Philip W.;Bander, Neil H.;Sweeney, Christopher;Farokhzad, Omid C.;Langer, Robert;Zale, Stephen

    We describe the development and clinical translation of a targeted polymeric nanoparticle (TNP) containing the chemotherapeutic docetaxel (DTXL) for the treatment of patients with solid tumors. DTXL-TNP is targeted to prostate-specific membrane antigen, a clinically validated tumor antigen expressed on prostate cancer cells and on the neovasculature of most nonprostate solid tumors. DTXL-TNP was developed from a combinatorial library of more than 100 TNP formulations varying with respect to particle size, targeting ligand density, surface hydrophilicity, drug loading, and drug release properties. Pharmacokinetic and tissue distribution studies in rats showed that the NPs had a blood circulation half-life of about 20 hours and minimal liver accumulation. In tumor-bearing mice, DTXL-TNP exhibited markedly enhanced tumor accumulation at 12 hours and prolonged tumor growth suppression compared to a solvent-based DTXL formulation (sb-DTXL). In tumor-bearing mice, rats, and nonhuman ...


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

Cet article passe en revue les diverses approches thérapeutiques visant à éradiquer les cellules souches du cancer

  • Cancer stem cells: In the line of fire
    Cancer treatment reviews, sous presse, 2012 (résumé)
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    Cet article passe en revue les diverses approches thérapeutiques visant à éradiquer les cellules souches du cancer

    “Cancer stem cells: In the line of fire”

    • Alison, Malcolm R.;Lin, Wey-Ran;Lim, Susan M. L.;Nicholson, Linda J.

    Most tumours appear to contain a sub-population (s) of self-renewing and expanding stem cells known as cancer stem cells (CSCs). The CSC model proposes that CSCs are at the apex of a hierarchically organized cell population, somewhat akin to normal tissue organization. Selection pressures may also facilitate the stochastic clonal expansion of sub-sets of cancer cells that may co-exist with CSCs and their progeny, moreover the trait of stemness may be more fluid than hitherto expected, and cells may switch between the stem and non-stem cell state. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In this review we discuss the basis of such resistance that highlights the roles of ABC transporters, aldehyde dehydrogenase (ALDH) activity, intracellular signalling pathways, the DNA damage response, hypoxia and proliferative quiescence as being significant determinants. In the light of such observations, we outline strategies ...


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

Traitements systémiques : applications cliniques

Cet article passe en revue les travaux récents sur le traitement des cancers du sein et analyse les défis posés par la traduction en clinique des résultats de recherches biologiques

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    Cet article passe en revue les travaux récents sur le traitement des cancers du sein et analyse les défis posés par la traduction en clinique des résultats de recherches biologiques

    “Toward Individualized Breast Cancer Therapy: Translating Biological Concepts to the Bedside”

    • Hortobagyi, Gabriel N.

    Abstract The management of breast cancer has changed dramatically over the past 20 years. Based on gene expression profiles, or proteomics of three or four biomarkers, it is apparent that there are multiple subtypes with different clinical characteristics, clinical courses, and sensitivities to existing therapies. This manuscript reviews the management of hormone receptor–positive, human epidermal growth factor receptor 2–positive, and triple-negative breast cancers, emphasizing changes that have occurred in recent years and focusing on potential mechanisms of drug resistance. I also highlight strategies to prevent or overcome resistance to specific therapeutic agents. As a result of enhanced biological understanding of the molecular anomalies that drive the development, progression, and dissemination of breast cancer, a number of novel, molecularly targeted agents have been added to standard therapies. Chemotherapy, endocrine therapy, and targeted treatments have markedly reduced ...


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

A partir de données portant sur 1 502 patientes atteintes d'un cancer du sein et incluses dans un essai allemand de traitement adjuvant, cette étude rétrospective met en évidence une corrélation entre la survenue d'événements indésirables et la réponse à un traitement au tamoxifène et/ou exémestane

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    A partir de données portant sur 1 502 patientes atteintes d'un cancer du sein et incluses dans un essai allemand de traitement adjuvant, cette étude rétrospective met en évidence une corrélation entre la survenue d'événements indésirables et la réponse à un traitement au tamoxifène et/ou exémestane

    “Correlation of treatment-emergent adverse events and clinical response to endocrine therapy in early breast cancer: a retrospective analysis of the German cohort of TEAM”

    • Hadji, P.;Kieback, D. G.;Tams, J.;Hasenburg, A.;Ziller, M.

    Background: Previous studies have suggested a correlation between the occurrence of vasomotor or joint symptoms during tamoxifen or aromatase inhibitor treatment and improved clinical response.Patients and methods: A retrospective analysis of the German cohort of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial was carried out to assess disease-free survival (DFS) and overall survival (OS) in patients with and without arthralgia/myalgia and/or menopausal symptoms during adjuvant endocrine treatment.Results: A total of 1502 patients were included; 739 patients received tamoxifen followed by exemestane and 763 received exemestane. Patients reporting arthralgia/myalgia and patients reporting menopausal symptoms during endocrine treatment had significantly longer OS and DFS than those not reporting these events. The effect on OS was irrespective of treatment. DFS was significantly improved in exemestane-treated patients reporting arthralgia/myalgia or those reporting ...


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

Mené sur 121 patientes atteintes d'un cancer du sein HER2+ de stade II à IIIA, cet essai de phase II évalue l'ajout de trastuzumab, de lapatinib ou d'une combinaison des deux traitements, à une chimiothérapie préopératoire

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    Mené sur 121 patientes atteintes d'un cancer du sein HER2+ de stade II à IIIA, cet essai de phase II évalue l'ajout de trastuzumab, de lapatinib ou d'une combinaison des deux traitements, à une chimiothérapie préopératoire

    “Preoperative Chemotherapy Plus Trastuzumab, Lapatinib, or Both in Human Epidermal Growth Factor Receptor 2–Positive Operable Breast Cancer: Results of the Randomized Phase II CHER-LOB Study”

    • Guarneri, Valentina;Frassoldati, Antonio;Bottini, Alberto;Cagossi, Katia;Bisagni, Giancarlo;Sarti, Samanta;Ravaioli, Alberto;Cavanna, Luigi;Giardina, Giovanni;Musolino, Antonino;Untch, Michael;Orlando, Laura;Artioli, Fabrizio;Boni, Corrado;Generali, Daniele Giulio;Serra, Patrizia;Bagnalasta, Michela;Marini, Luca;Piacentini, Federico;D'Amico, Roberto;Conte, PierFranco

    Purpose This is a noncomparative, randomized, phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab plus lapatinib in patients with human epidermal growth factor receptor 2 (HER2) –positive, stage II to IIIA operable breast cancer. The primary aim was to estimate the percentage of pathologic complete response (pCR; no invasive tumor in breast and axillary nodes).Patients and Methods In the three arms, chemotherapy consisted of weekly paclitaxel (80 mg/m2) for 12 weeks followed by fluorouracil, epirubicin, and cyclophosphamide for four courses every 3 weeks. The patients randomly assigned to arm A received a 4-mg loading dose of trastuzumab followed by 2 mg weekly; in arm B patients received lapatinib 1,500 mg orally (PO) daily; and in arm C, patients received trastuzumab and lapatinib 1,000 mg PO daily.Results A total of 121 patients were randomly assigned. Diarrhea and dermatologic and hepatic toxicities were ...


  • Neoadjuvant Trials of Human Epidermal Growth Factor Receptor 2 Targeting: How Many Drugs Do We Need?
    Journal of Clinical Oncology, sous presse, 2012 (éditorial en libre accès)
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    Mené sur 121 patientes atteintes d'un cancer du sein HER2+ de stade II à IIIA, cet essai de phase II évalue l'ajout de trastuzumab, de lapatinib ou d'une combinaison des deux traitements, à une chimiothérapie préopératoire

    “Neoadjuvant Trials of Human Epidermal Growth Factor Receptor 2 Targeting: How Many Drugs Do We Need?”

    • Carey, Lisa A.


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

A partir d'une revue de la littérature (4 essais ayant inclus un total de 663 patients), cette méta-analyse compare, du point de vue de la survie globale, deux chimiothérapies (cisplatine et carboplatine) en traitement de première ligne d'un cancer du poumon à petites cellules

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    A partir d'une revue de la littérature (4 essais ayant inclus un total de 663 patients), cette méta-analyse compare, du point de vue de la survie globale, deux chimiothérapies (cisplatine et carboplatine) en traitement de première ligne d'un cancer du poumon à petites cellules

    “Carboplatin- or Cisplatin-Based Chemotherapy in First-Line Treatment of Small-Cell Lung Cancer: The COCIS Meta-Analysis of Individual Patient Data”

    • Rossi, Antonio;Di Maio, Massimo;Chiodini, Paolo;Rudd, Robin Michael;Okamoto, Hiroaki;Skarlos, Dimosthenis Vasilios;Früh, Martin;Qian, Wendi;Tamura, Tomohide;Samantas, Epaminondas;Shibata, Taro;Perrone, Francesco;Gallo, Ciro;Gridelli, Cesare;Martelli, Olga;Lee, Siow-Ming

    Purpose Since treatment efficacy of cisplatin- or carboplatin-based chemotherapy in the first-line treatment of small-cell lung cancer (SCLC) remains contentious, a meta-analysis of individual patient data was performed to compare the two treatments.Patients and Methods A systematic review identified randomized trials comparing cisplatin with carboplatin in the first-line treatment of SCLC. Individual patient data were obtained from coordinating centers of all eligible trials. The primary end point was overall survival (OS). All statistical analyses were stratified by trial. Secondary end points were progression-free survival (PFS), objective response rate (ORR), and treatment toxicity. OS and PFS curves were compared by using the log-rank test. ORR was compared by using the Mantel-Haenszel test.Results Four eligible trials with 663 patients (328 assigned to cisplatin and 335 to carboplatin) were included in the analysis. Median OS was 9.6 months for cisplatin and 9.4 months for ...


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

Cet article passe en revue les travaux récents sur le traitement des cancers du poumon non à petites cellules présentant des réarrangements du gène ALK

  • Treating ALK-positive lung cancer[mdash]early successes and future challenges
    Nature Reviews Clinical Oncology, sous presse, 2012 (résumé)
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    Cet article passe en revue les travaux récents sur le traitement des cancers du poumon non à petites cellules présentant des réarrangements du gène ALK

    “Treating ALK-positive lung cancer[mdash]early successes and future challenges”

    • Camidge, D. Ross;Doebele, Robert C.

    Rearrangements of the anaplastic lymphoma kinase (ALK) gene occur infrequently in non-small-cell lung cancer (NSCLC), but provide an important paradigm for oncogene-directed therapy in this disease. Crizotinib, an orally bioavailable inhibitor of ALK, provides significant benefit for patients with ALK-positive (ALK+) NSCLC in association with characteristic, mostly mild, toxic effects, and this drug has been approved by the FDA for clinical use in this molecularly defined subgroup of lung cancer. Many new ALK inhibitors are being developed and understanding the challenges of determining and addressing the adverse effects that are likely to be ALK specific, while maximizing the time of benefit on targeted agents, and understanding the mechanisms that underlie drug resistance will be critical in the future for informing the optimal therapy of ALK+ NSCLC.


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

Cet article passe en revue les travaux récents sur le développement de thérapies ciblées pour le traitement des patients atteints de mélanome

  • From genes to drugs: targeted strategies for melanoma
    Nature Reviews Cancer, sous presse, 2012 (résumé)
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    Cet article passe en revue les travaux récents sur le développement de thérapies ciblées pour le traitement des patients atteints de mélanome

    “From genes to drugs: targeted strategies for melanoma”

    • Flaherty, Keith T.;Hodi, F. Stephen;Fisher, David E.

    The past decade has revealed that melanoma is comprised of multiple subclasses that can be categorized on the basis of key features, including the clinical stage of disease, the oncogenic molecular 'drivers', the anatomical location or the behaviour of the primary lesion and the expression of specific biomarkers. Although exercises in subclassification are not new in oncology, progress in this area has produced both conceptual and clinical breakthroughs, which, for melanoma, are unprecedented in the modern history of the disease. This Review focuses on these recent striking advances in the strategy of molecularly targeted approaches to the therapy of melanoma in humans.


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

Mené sur 39 patients atteints d'une leucémie lymphocytaire chronique présentant une délétion du gène TP53, cet essai de phase II évalue un traitement combinant alemtuzumab, un anticorps monoclonal anti CD52, et méthylprednisolone

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    Mené sur 39 patients atteints d'une leucémie lymphocytaire chronique présentant une délétion du gène TP53, cet essai de phase II évalue un traitement combinant alemtuzumab, un anticorps monoclonal anti CD52, et méthylprednisolone

    “Alemtuzumab in Combination With Methylprednisolone Is a Highly Effective Induction Regimen for Patients With Chronic Lymphocytic Leukemia and Deletion of TP53: Final Results of the National Cancer Research Institute CLL206 Trial”

    • Pettitt, Andrew R.;Jackson, Richard;Carruthers, Stacey;Dodd, James;Dodd, Susanna;Oates, Melanie;Johnson, Gillian G.;Schuh, Anna;Matutes, Estella;Dearden, Claire E.;Catovsky, Daniel;Radford, John A.;Bloor, Adrian;Follows, George A.;Devereux, Stephen;Kruger, Anton;Blundell, Julie;Agrawal, Samir;Allsup, David;Proctor, Stephen;Heartin, Earnest;Oscier, David;Hamblin, Terry J.;Rawstron, Andrew;Hillmen, Peter

    Purpose In chronic lymphocytic leukemia (CLL), TP53 deletion/mutation is strongly associated with an adverse outcome and resistance to chemotherapy-based treatment. In contrast, TP53 defects are not associated with resistance to the anti-CD52 monoclonal antibody alemtuzumab or methylprednisolone. In an attempt to improve the treatment of TP53-defective CLL, a multicenter phase II study was developed to evaluate alemtuzumab and methylprednisolone in combination.Patients and Methods Thirty-nine patients with TP53-deleted CLL (17 untreated and 22 previously treated) received up to 16 weeks of treatment with alemtuzumab 30 mg three times a week and methylprednisolone 1.0 g/m2 for five consecutive days every 4 weeks. Antimicrobial prophylaxis consisted of cotrimoxazole, itraconazole, and aciclovir (or valganciclovir for asymptomatic cytomegalovirus viremia). The primary end point was response as assigned by an end-point review committee. Secondary end points were safety, progression-free ...


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

Mené sur 280 patients atteints d'une leucémie myéloïde aiguë et traités dans 26 hôpitaux français, cet essai de phase III évalue, du point de vue de la survie sans événement, l'ajout de gemtuzumab ogamicine, un conjugué anticorps anti-CD 33, à une chimiothérapie de première ligne

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    Mené sur 280 patients atteints d'une leucémie myéloïde aiguë et traités dans 26 hôpitaux français, cet essai de phase III évalue, du point de vue de la survie sans événement, l'ajout de gemtuzumab ogamicine, un conjugué anticorps anti-CD 33, à une chimiothérapie de première ligne

    “Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study”

    • Castaigne, Sylvie;Pautas, Cécile;Terré, Christine;Raffoux, Emmanuel;Bordessoule, Dominique;Bastie, Jean-Noel;Legrand, Ollivier;Thomas, Xavier;Turlure, Pascal;Reman, Oumedaly;de Revel, Thierry;Gastaud, Lauris;de Gunzburg, Noémie;Contentin, Nathalie;Henry, Estelle;Marolleau, Jean-Pierre;Aljijakli, Ahmad;Rousselot, Philippe;Fenaux, Pierre;Preudhomme, Claude;Chevret, Sylvie;Dombret, Hervé

    The results of the addition of gemtuzumab ozogamicin, an anti-CD33 antibody conjugate, to the standard treatment for patients with acute myeloid leukaemia in phase 3 trials were contradictory. We investigated whether the addition of low fractionated-dose gemtuzumab ozogamicin to standard front-line chemotherapy would improve the outcome of patients with this leukaemia without causing excessive toxicity. In a phase 3, open-label study, undertaken in 26 haematology centres in France, patients aged 50-70 years with previously untreated de novo acute myeloid leukaemia were randomly assigned with a computer-generated sequence in a 1:1 ratio with block sizes of four to standard treatment (control group) with or without five doses of intravenous gemtuzumab ozogamicin (3 mg/m2on days 1, 4, and 7 during induction and day 1 of each of the two consolidation chemotherapy courses). The primary endpoint was event-free survival (EFS). Secondary endpoints were relapse-free (RFS), overall survival ...


  • Treatment of AML: resurrection for gemtuzumab ozogamicin?
    The Lancet, sous presse, 2012 (commentaire)
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    Mené sur 280 patients atteints d'une leucémie myéloïde aiguë et traités dans 26 hôpitaux français, cet essai de phase III évalue, du point de vue de la survie sans événement, l'ajout de gemtutzumab ogamicine, un conjugué anticorps anti-CD 33, à une chimiothérapie de première ligne

    “Treatment of AML: resurrection for gemtuzumab ozogamicin?”

    • Estey, Elihu


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

A partir de données issues de deux essais européens menés sur des patients atteints d'une leucémie promyélocytaire aiguë, cette étude compare les caractéristiques et l'évolution de la maladie entre les enfants, les adolescents et les adultes

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    A partir de données issues de deux essais européens menés sur des patients atteints d'une leucémie promyélocytaire aiguë, cette étude compare les caractéristiques et l'évolution de la maladie entre les enfants, les adolescents et les adultes

    “Outcome of Acute Promyelocytic Leukemia (APL) in Children and Adolescents: An Analysis in Two Consecutive Trials of the European APL Group”

    • Bally, Cecile;Fadlallah, Jehane;Leverger, Guy;Bertrand, Yves;Robert, Alain;Baruchel, Andre;Guerci, Agnes;Recher, Christian;Raffoux, Emmanuel;Thomas, Xavier;Leblanc, Thierry;Idres, Nadia;Cassinat, Bruno;Vey, Norbert;Chomienne, Christine;Dombret, Herve;Sanz, Miguel;Fenaux, Pierre;Adès, Lionel

    Purpose Acute promyelocytic leukemia (APL) is rare in children. All-trans-retinoic acid (ATRA) combined with chemotherapy, the reference treatment of APL, is generally considered to produce similar results in children and adults. However, previously published childhood APL studies have generally analyzed all patients age < 18 years as a group, without further dividing according to age.Patients and Methods We compared disease characteristics and outcomes of children (age ≤ 12 years), adolescents (13 to 18 years), and adults (> 18 years) included in two multicenter APL clinical trials (APL 93 and 2000 trials).Results Of the 833 patients age ≤ 60 years included in the two trials, 26 (3%), 58 (7%), and 749 (90%) were children, adolescents, and adults, respectively. Children had significantly higher baseline WBC counts (P < .001). The complete remission (CR) rate (92%, 100%, and 94.5%, respectively) and 5-year cumulative incidence of relapse (CIR; 28%, 20%, and 23%, respectively) did ...


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

Mené sur 571 patients atteints d'un cancer colorectal métastatique, cet essai multicentrique de phase III évalue, du point de vue de la survie sans progression, l'ajout de cetuximab à une chimiothérapie Nordic FLOX, administrée en continue ou de façon intermittente, en traitement de première ligne

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    Mené sur 571 patients atteints d'un cancer colorectal métastatique, cet essai multicentrique de phase III évalue, du point de vue de la survie sans progression, l'ajout de cetuximab à une chimiothérapie Nordic FLOX, administrée en continue ou de façon intermittente, en traitement de première ligne

    “Phase III Trial of Cetuximab With Continuous or Intermittent Fluorouracil, Leucovorin, and Oxaliplatin (Nordic FLOX) Versus FLOX Alone in First-Line Treatment of Metastatic Colorectal Cancer: The NORDIC-VII Study”

    • Tveit, Kjell Magne;Guren, Tormod;Glimelius, Bengt;Pfeiffer, Per;Sorbye, Halfdan;Pyrhonen, Seppo;Sigurdsson, Fridbjorn;Kure, Elin;Ikdahl, Tone;Skovlund, Eva;Fokstuen, Tone;Hansen, Flemming;Hofsli, Eva;Birkemeyer, Elke;Johnsson, Anders;Starkhammar, Hans;Yilmaz, Mette Karen;Keldsen, Nina;Erdal, Anne Berit;Dajani, Olav;Dahl, Olav;Christoffersen, Thoralf

    Purpose The NORDIC-VII multicenter phase III trial investigated the efficacy of cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic FLOX), administered continuously or intermittently, in previously untreated metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on treatment outcome was also investigated.Patients and Methods Patients were randomly assigned to receive either standard Nordic FLOX (arm A), cetuximab and FLOX (arm B), or cetuximab combined with intermittent FLOX (arm C). Primary end point was progression-free survival (PFS). Overall survival (OS), response rate, R0 resection rate, and safety were secondary end points.Results Of the 571 patients randomly assigned, 566 were evaluable in intention-to-treat (ITT) analyses. KRAS and BRAF mutation analyses were obtained in 498 (88%) and 457 patients (81%), respectively. KRAS mutations were present in 39% of the tumors; 12% of tumors had BRAF mutations. The presence of BRAF ...


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

Cet article passe en revue les résultats d'essais de phase II et III évaluant le bévacizumab en traitement de première ligne chez les patients atteints d'un cancer colorectal métastatique

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    Cet article passe en revue les résultats d'essais de phase II et III évaluant le bévacizumab en traitement de première ligne chez les patients atteints d'un cancer colorectal métastatique

    “Bevacizumab-Based Therapies in the First-Line Treatment of Metastatic Colorectal Cancer”

    • Strickler, John H.;Hurwitz, Herbert I.

    Abstract Since its approval for the first-line treatment of metastatic colorectal cancer (mCRC), bevacizumab has become a standard treatment option in combination with chemotherapy for patients with mCRC. Bevacizumab has demonstrated efficacy in combination with a number of different backbone chemotherapy regimens, and its widespread use has introduced several important questions regarding the selection and optimization of bevacizumab-based treatment regimens, its use in various patient populations, and the identification of associated adverse events. This review discusses the results of several phase II and phase III clinical trials, as well as large observational studies, to address the use of bevacizumab in the treatment of patients with mCRC in the first-line setting.


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

Mené sur 2 686 patients ayant subi une résection d'un cancer colorectal de stade III sans mutation KRAS, cet essai évalue, du point de vue de la survie sans récidive, l'ajout de cetuximab à une chimiothérapie mFOLFOX6 (durée médiane de suivi : 28 mois)

  • Effect of Oxaliplatin, Fluorouracil, and Leucovorin With or Without Cetuximab on Survival Among Patients With Resected Stage III Colon Cancer
    JAMA: The Journal of the American Medical Association, Vol. 307 (13), pp. 1383-1393, 2012 (résumé)
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    Mené sur 2 686 patients ayant subi une résection d'un cancer colorectal de stade III sans mutation KRAS, cet essai évalue, du point de vue de la survie sans récidive, l'ajout de cetuximab à une chimiothérapie mFOLFOX6 (durée médiane de suivi : 28 mois)

    “Effect of Oxaliplatin, Fluorouracil, and Leucovorin With or Without Cetuximab on Survival Among Patients With Resected Stage III Colon Cancer”

    • Alberts, Steven R.;Sargent, Daniel J.;Nair, Suresh;Mahoney, Michelle R.;Mooney, Margaret;Thibodeau, Stephen N.;Smyrk, Thomas C.;Sinicrope, Frank A.;Chan, Emily;Gill, Sharlene;Kahlenberg, Morton S.;Shields, Anthony F.;Quesenberry, James T.;Webb, Thomas A.;Farr, Gist H.;Pockaj, Barbara A.;Grothey, Axel;Goldberg, Richard M.

    Context Leucovorin, fluorouracil, and oxaliplatin (FOLFOX) is the standard adjuvant therapy for resected stage III colon cancer. Adding cetuximab to FOLFOX benefits patients with metastatic wild-type KRAS but not mutated KRAS colon cancer.Objective To assess the potential benefit of cetuximab added to the modified sixth version of the FOLFOX regimen (mFOLFOX6) in patients with resected stage III wild-type KRAS colon cancer.Design, Setting, and Participants A randomized trial of 2686 patients aged 18 years or older at multiple institutions across North America enrolled following resection and informed consent between February 10, 2004, and November 25, 2009. The primary randomized comparison was 12 biweekly cycles of mFOLFOX6 with and without cetuximab. KRAS mutation status was centrally determined. The trial was halted after a planned interim analysis of 48% of predicted events (246/515) occurring in 1863 (of 2070 planned) patients with tumors having wild-type KRAS. A total of 717 ...


  • Antitumor Activity in Metastatic Disease Does Not Predict Efficacy in the Adjuvant Setting
    JAMA: The Journal of the American Medical Association, Vol. 307 (13), pp. 1431-1432, 2012 (éditorial)
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    Mené sur 2 686 patients ayant subi une résection d'un cancer colorectal de stade III sans mutation KRAS, cet essai évalue, du point de vue de la survie sans récidive, l'ajout de cetuximab à une chimiothérapie mFOLFOX6 (durée médiane de suivi : 28 mois)

    “Antitumor Activity in Metastatic Disease Does Not Predict Efficacy in the Adjuvant Setting”

    • Segal, Neil H. ; Saltz, Leonard B.


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

Menée sur une cohorte de 1 362 patients ayant survécu plus de 5 ans à un cancer diagnostiqué entre 1966 et 1996, cette étude néerlandaise évalue les risques à long terme d'événements cardiovasculaires de grade supérieur ou égal à 3 associés aux traitements

  • High Risk of Symptomatic Cardiac Events in Childhood Cancer Survivors
    Journal of Clinical Oncology, sous presse, 2012 (résumé)
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    Menée sur une cohorte de 1 362 patients ayant survécu plus de 5 ans à un cancer diagnostiqué entre 1966 et 1996, cette étude néerlandaise évalue les risques à long terme d'événements cardiovasculaires de grade supérieur ou égal à 3 associés aux traitements

    “High Risk of Symptomatic Cardiac Events in Childhood Cancer Survivors”

    • van der Pal, Helena J.;van Dalen, Elvira C.;van Delden, Evelien;van Dijk, Irma W.;Kok, Wouter E.;Geskus, Ronald B.;Sieswerda, Elske;Oldenburger, Foppe;Koning, Caro C.;van Leeuwen, Flora E.;Caron, Huib N.;Kremer, Leontien C.

    Purpose To evaluate the long-term risk for validated symptomatic cardiac events (CEs) and associated risk factors in childhood cancer survivors (CCSs).Patients and Methods We determined CEs grade 3 or higher: congestive heart failure (CHF), cardiac ischemia, valvular disease, arrhythmia and/or pericarditis (according to Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) in a hospital-based cohort of 1,362 5-year CCSs diagnosed between 1966 and 1996. We calculated both marginal and cause-specific cumulative incidence of CEs and cause-specific cumulative incidence of separate events. We analyzed different risk factors in multivariable Cox regression models.Results Overall, 50 CEs, including 27 cases of CHF, were observed in 42 survivors (at a median attained age of 27.1 years). The 30-year cause-specific cumulative incidence of CEs was significantly increased after treatment with both anthracyclines and cardiac irradiation (12.6%; 95% CI, 4.3% to 20.3%), after ...


  • Getting to the Heart of the Matter
    Journal of Clinical Oncology, sous presse, 2012 (éditorial en libre accès)
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    Menée sur une cohorte de 1 362 patients ayant survécu plus de 5 ans à un cancer diagnostiqué entre 1966 et 1996, cette étude néerlandaise évalue les risques à long terme d'événements cardiovasculaires de grade supérieur ou égal à 3 associés aux traitements

    “Getting to the Heart of the Matter”

    • Davies, Stella M.


Mots clés : Cancer (général); Traitements (Traitements systémiques : applications cliniques)

Combinaison de traitements localisés et systémiques

Cet article fait le point sur les produits à base d'acides nucléiques actuellement utilisés dans certaines approches thérapeutiques pour sensibiliser les cellules de carcinome nasopharyngé aux rayonnements ionisants

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    Cet article fait le point sur les produits à base d'acides nucléiques actuellement utilisés dans certaines approches thérapeutiques pour sensibiliser les cellules de carcinome nasopharyngé aux rayonnements ionisants

    “Potential Use of Nucleic Acid-based Agents in the Sensitization of Nasopharyngeal Carcinoma to Radiotherapy”

    • Zhang, Lu;Yang, Lifang;Li, Jian Jian;Sun, Lunquan

    Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer. The two-year survival rate of patients with stage III or IV disease is only about 50%. Due to its high radiosensitivity, radiotherapy is the standard treatment for early-stage of NPC. However, the radioresistance observed in some patients can cause distant metastases and local recurrence after radiotherapy. Special emphasis has been given to the discovery of effective radiosensitizers. Oncogenic proteins encoded by EBV genomes may serve as part of targeted radiosensitization, such as NF кB-mediated expression of latent membrane protein-1. We here review the major nucleic acid-based options currently used in cancer therapeutic approaches and the selected candidate genes that can be targeted for NPC radiosensitization.


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

Mené sur 194 patients atteints d'un carcinome épidermoïde de l'hypopharynx (durée médiane de suivi : 10,5 ans), cet essai évalue, du point de vue de la survie globale, les résultats cliniques d'un traitement chirurgical préservant le larynx en combinaison avec une chimiothérapie d'induction

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    Mené sur 194 patients atteints d'un carcinome épidermoïde de l'hypopharynx (durée médiane de suivi : 10,5 ans), cet essai évalue, du point de vue de la survie globale, les résultats cliniques d'un traitement chirurgical préservant le larynx en combinaison avec une chimiothérapie d'induction

    “Laryngeal preservation with induction chemotherapy for hypopharyngeal squamous cell carcinoma: 10-year results of EORTC trial 24891”

    • Lefebvre, J.-L.;Andry, G.;Chevalier, D.;Luboinski, B.;Collette, L.;Traissac, L.;de Raucourt, D.;Langendijk, J. A.

    Background: We report the 10-year results of the EORTC trial 24891 comparing a larynx-preservation approach to immediate surgery in hypopharynx and lateral epilarynx squamous cell carcinoma.Material and methods: Two hundred and two patients were randomized to either the surgical approach (total laryngectomy with partial pharyngectomy and neck dissection, followed by irradiation) or to the chemotherapy arm up to three cycles of induction chemotherapy (cisplatin 100 mg/m2 day 1 + 5-FU 1000 mg/m2 day 1–5) followed for complete responders by irradiation and otherwise by conventional treatment. The end points were overall survival [OS, noninferiority: hazard ratio (preservation/surgery) ≤1.428, one-sided α = 0.05], progression-free survival (PFS) and survival with a functional larynx (SFL).Results: At a median follow-up of 10.5 years on 194 eligible patients, disease evolution was seen in 54 and 49 patients in the surgery and chemotherapy arm, respectively, and 81 and 83 patients had ...


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

Mené sur 24 patients atteints d'un glioblastome multiforme nouvellement diagnostiqué (âge : 27 à 77 ans ; durée médiane de suivi : 14,8 mois), cet essai de phase II évalue, du point de vue de la survie globale, la toxicité et l'efficacité d'une radiothérapie hypofractionnée avec modulation d'intensité en combinaison avec une chimiothérapie par témozolomide

  • Phase II Trial of Hypofractionated IMRT With Temozolomide for Patients With Newly Diagnosed Glioblastoma Multiforme
    International journal of radiation oncology, biology, physics, sous presse, 2012 (résumé)
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    Mené sur 24 patients atteints d'un glioblastome multiforme nouvellement diagnostiqué (âge : 27 à 77 ans ; durée médiane de suivi : 14,8 mois), cet essai de phase II évalue, du point de vue de la survie globale, la toxicité et l'efficacité d'une radiothérapie hypofractionnée avec modulation d'intensité en combinaison avec une chimiothérapie par témozolomide

    “Phase II Trial of Hypofractionated IMRT With Temozolomide for Patients With Newly Diagnosed Glioblastoma Multiforme”

    • Reddy, Krishna;Damek, Denise;Gaspar, Laurie E.;Ney, Douglas;Waziri, Allen;Lillehei, Kevin;Stuhr, Kelly;Kavanagh, Brian D.;Chen, Changhu

    To report toxicity and overall survival (OS) in patients with newly diagnosed glioblastoma multiforme (GBM) treated with hypofractionated intensity-modulated radiotherapy (hypo-IMRT) with concurrent and adjuvant temozolomide (TMZ). Patients with newly diagnosed GBM after biopsy or resection and with adequate performance status and organ or bone marrow function were eligible for this study. Patients received postoperative hypo-IMRT to the surgical cavity and residual tumor seen on T1-weighted brain MRI with a 5-mm margin to a total dose of 60 Gy in 10 fractions (6 Gy/fraction) and to the T2 abnormality on T2-weighted MRI with 5-mm margin to 30 Gy in 10 fractions (3 Gy/fraction). Concurrent TMZ was given at 75 mg/m2/day for 28 consecutive days. Adjuvant TMZ was given at 150 to 200 mg/m2/day for 5 days every 28 days. Toxicities were defined using Common Terminology Criteria for Adverse Events version 3.0. Twenty-four patients were treated, consisting of 14 men, 10 women; a median age of ...


Mots clés : Système nerveux central; Traitements (Combinaison de traitements localisés et systémiques)

Mené sur 264 patients atteints d'un cancer localisé de la prostate de stade T3-4 ou pT3N0M0, cet essai multicentrique randomisé de phase 3 évalue, du point de vue de la survie et du contrôle locorégional de la maladie, l'intérêt de combiner une radiothérapie à un traitement anti-androgénique à long terme

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    Mené sur 264 patients atteints d'un cancer localisé de la prostate de stade T3-4 ou pT3N0M0, cet essai multicentrique randomisé de phase 3 évalue, du point de vue de la survie et du contrôle locorégional de la maladie, l'intérêt de combiner une radiothérapie à un traitement anti-androgénique à long terme

    “Addition of Radiotherapy to Long-Term Androgen Deprivation in Locally Advanced Prostate Cancer: An Open Randomised Phase 3 Trial”

    • Nicolas, Mottet;Michel, Peneau;Jean-Jacques, Mazeron;Vincent, Molinie;Pierre, Richaud

    Background : Radiotherapy combined with androgen-deprivation therapy (ADT) is superior to radiotherapy alone in localised prostate cancer; however, data comparing ADT alone are somewhat limited. Objective :To compare 3-yr ADT plus radiotherapy with ADT alone in locally advanced prostate cancer patients. Design, setting, and participants : A multicentre randomised open controlled phase 3 trial in 264 histologically confirmed T3–4 or pT3N0M0 prostate cancer patients randomised from March 2000 to December 2003. Intervention : ADT (11.25 mg subcutaneous depot injection of leuprorelin every 3 mo for 3 yr) plus external-beam radiotherapy or ADT alone. Flutamide (750 g/d) was administered for 1 mo. Outcome measurements and statistical analysis : The primary objective was 5 yr progression-free survival (PFS) according to clinical or biologic criteria, using the American Society for Therapeutic Radiology and Oncology (ASTRO) and the newer (Phoenix) definition (nadir plus 2 ng/ml), by ...


Mots clés : Prostate; Traitements (Combinaison de traitements localisés et systémiques)

Mené sur 21 patients atteints d'un cancer de l'œsophage localement avancé et non résécable, cet essai de phase II évalue, du point de vue de la survie globale à deux ans, l'efficacité et la toxicité d'un traitement définitif par cetuximab - cisplatine - irinotécan en combinaison avec une radiothérapie thoracique

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    Mené sur 21 patients atteints d'un cancer de l'œsophage localement avancé et non résécable, cet essai de phase II évalue, du point de vue de la survie globale à deux ans, l'efficacité et la toxicité d'un traitement définitif par cetuximab - cisplatine - irinotécan en combinaison avec une radiothérapie thoracique

    “Cetuximab Plus Cisplatin, Irinotecan, and Thoracic Radiotherapy as Definitive Treatment for Locally Advanced, Unresectable Esophageal Cancer: A Phase-II Study of The SWOG (S0414)”

    • Tomblyn, Michael B.;Goldman, Bryan H.;Thomas, Charles R. Jr;Benedetti, Jacqueline K.;Lenz, Heinz-Josef;Mehta, Vivek;Beeker, Thaddeus;Gold, Philip J.;Abbruzzese, James L.;Blanke, Charles D.;for the SWOG GI Committee

    Introduction: The specific aims of the study were to evaluate the 2-year overall survival (OS) and progression-free survival (PFS), toxicity profile, and best objective response rate in patients with locally advanced, clinically unresectable esophageal cancer receiving cetuximab, cisplatin, irinotecan, and thoracic radiotherapy (TRT) within a multi-institutional cooperative-group setting. Methods: Eligible patients (cT4 M0 or medically unresectable, biopsy proven, and noncervical esophageal cancer) were to receive four 21-day cycles of cetuximab 400 mg/m2 (day 1, cycle 1), cetuximab 250 mg/m2 (day 8, 15, cycle 1; then days 1, 8, and 15 for subsequent cycles), cisplatin 30 mg/m2 (days 1 and 8, all cycles), and irinotecan 65 mg/m2 (days 1 and 8, all cycles). TRT was administered at 1.8 Gy in 28 daily fractions to a total dose of 50.4 Gy, to begin with on day 1 of cycle 3. The primary endpoint was 2-year OS, with an accrual goal of 75 patients with adenocarcinoma. Results: The study was ...


Mots clés : Oesophage; Traitements (Combinaison de traitements localisés et systémiques)

Mené sur 2 126 patients (âge : 18 à 60 ans) atteints d'un lymphome hodgkinien nouvellement diagnostiqué et de stade avancé, cet essai multicentrique allemand de phase 3 compare l'efficacité et la toxicité de deux protocoles de chimiothérapie d'intensité réduite en combinaison avec une radiothérapie guidée par tomographie par émission de positons

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    Mené sur 2 126 patients (âge : 18 à 60 ans) atteints d'un lymphome hodgkinien nouvellement diagnostiqué et de stade avancé, cet essai multicentrique allemand de phase 3 compare l'efficacité et la toxicité de deux protocoles de chimiothérapie d'intensité réduite en combinaison avec une radiothérapie guidée par tomographie par émission de positons

    “Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial”

    • Engert, Andreas;Haverkamp, Heinz;Kobe, Carsten;Markova, Jana;Renner, Christoph;Ho, Antony;Zijlstra, Josée;Král, Zdenek;Fuchs, Michael;Hallek, Michael;Kanz, Lothar;Döhner, Hartmut;Dörken, Bernd;Engel, Nicole;Topp, Max;Klutmann, Susanne;Amthauer, Holger;Bockisch, Andreas;Kluge, Regine;Kratochwil, Clemens;Schober, Otmar;Greil, Richard;Andreesen, Reinhard;Kneba, Michael;Pfreundschuh, Michael;Stein, Harald;Eich, Hans Theodor;Müller, Rolf-Peter;Dietlein, Markus;Borchmann, Peter;Diehl, Volker

    The intensity of chemotherapy and need for additional radiotherapy in patients with advanced stage Hodgkin's lymphoma has been unclear. We did a prospective randomised clinical trial comparing two reduced-intensity chemotherapy variants with our previous standard regimen. Chemotherapy was followed by PET-guided radiotherapy. In this parallel group, open-label, multicentre, non-inferiority trial (HD15), 2182 patients with newly diagnosed advanced stage Hodgkin's lymphoma aged 18?60 years were randomly assigned to receive either eight cycles of BEACOPPescalated(8×Bescgroup), six cycles of BEACOPPescalated(6×Bescgroup), or eight cycles of BEACOPP14(8×B14group). Randomisation (1:1:1) was done centrally by stratified minimisation. Non-inferiority of the primary endpoint, freedom from treatment failure, was assessed using repeated CIs for the hazard ratio (HR) according to the intention-to-treat principle. Patients with a persistent mass after chemotherapy measuring 2·5 cm or larger and ...


  • Escalated BEACOPP in advanced Hodgkin's lymphoma
    The Lancet, sous presse, 2012 (commentaire)
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    Mené sur 2 126 patients (âge : 18 à 60 ans) atteints d'un lymphome hodgkinien nouvellement diagnostiqué et de stade avancé, cet essai multicentrique allemand de phase 3 compare l'efficacité et la toxicité de deux protocoles de chimiothérapie d'intensité réduite en combinaison avec une radiothérapie guidée par tomographie par émission de positons

    “Escalated BEACOPP in advanced Hodgkin's lymphoma”

    • Casasnovas, Olivier ; Coiffier, Bertrand


Mots clés : Lymphome; Traitements (Combinaison de traitements localisés et systémiques)

Menée sur 725 patients atteints d'un carcinome rectal localement avancé et diagnostiqué entre 1993 et 2008, cette étude rétrospective évalue l'association entre la réponse tumorale à une chimioradiothérapie pré-opératoire et les résultats cliniques à 5 ans

  • Neoadjuvant Treatment Response As an Early Response Indicator for Patients With Rectal Cancer
    Journal of Clinical Oncology, sous presse, 2012 (résumé)
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    Menée sur 725 patients atteints d'un carcinome rectal localement avancé et diagnostiqué entre 1993 et 2008, cette étude rétrospective évalue l'association entre la réponse tumorale à une chimioradiothérapie pré-opératoire et les résultats cliniques à 5 ans

    “Neoadjuvant Treatment Response As an Early Response Indicator for Patients With Rectal Cancer”

    • Park, In Ja;You, Y. Nancy;Agarwal, Atin;Skibber, John M.;Rodriguez-Bigas, Miguel A.;Eng, Cathy;Feig, Barry W.;Das, Prajnan;Krishnan, Sunil;Crane, Christopher H.;Hu, Chung-Yuan;Chang, George J.

    Purpose Neoadjuvant chemoradiotherapy for rectal cancer is associated with improved local control and may result in complete tumor response. Associations between tumor response and disease control following radical resection should be established before tumor response is used to evaluate treatment strategies. The purpose of this study was to assess and compare oncologic outcomes associated with the degree of pathologic response after chemoradiotherapy.Patients and Methods All patients with locally advanced (cT3-4 or cN+ by endorectal ultrasonography, computed tomography, or magnetic resonance imaging) rectal carcinoma diagnosed from 1993 to 2008 at our institution and treated with preoperative chemoradiotherapy and radical resection were identified, and their records were retrospectively reviewed. The median radiation dose was 50.4 Gy with concurrent chemotherapy. Recurrence-free survival (RFS), distant metastasis (DM), and local recurrence (LR) rates were compared among patients with ...


Mots clés : Colon-rectum; Traitements (Combinaison de traitements localisés et systémiques)

Ressources et infrastructures (Traitements)

Cet article propose des méthodes pour évaluer l'efficacité clinique et le rapport coût-efficacité de nouvelles technologies de radiothérapie

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    Cet article propose des méthodes pour évaluer l'efficacité clinique et le rapport coût-efficacité de nouvelles technologies de radiothérapie

    “Evaluation of novel radiotherapy technologies: what evidence is needed to assess their clinical and cost effectiveness, and how should we get it?”

    • van Loon, Judith;Grutters, Janneke;Macbeth, Fergus

    Technical innovations in radiation oncology—eg, intensity-modulated radiotherapy, stereotactic radiotherapy, and particle therapy—can be developed rapidly and introduced into the clinic even when costs associated with their use are much higher than those for conventional radiotherapy. Although clinical benefit is expected on the basis of superior biological and physical characteristics, data for clinical effectiveness of new radiotherapy techniques are scarce. Evidence from randomised clinical trials would be ideal but such studies focus mostly on new drugs. High investment costs and modifications over time make evaluation of novel radiotherapy technologies in clinical trials more complex. Here, we propose an algorithm for evaluation of the clinical and cost effectiveness of novel radiotherapy technologies. We suggest situations when randomised trials might be feasible and the type of trial that should be undertaken when they are not. Furthermore, we discuss the usefulness of ...


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

Cet article présente les recommandations d'un groupe d'experts de l'"American Society of Clinical Oncology" sur le dosage des chimiothérapies cytotoxiques pour les patients adultes obèses

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    Cet article présente les recommandations d'un groupe d'experts de l'"American Society of Clinical Oncology" sur le dosage des chimiothérapies cytotoxiques pour les patients adultes obèses

    “Appropriate Chemotherapy Dosing for Obese Adult Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline”

    • Griggs, Jennifer J.;Mangu, Pamela B.;Anderson, Holly;Balaban, Edward P.;Dignam, James J.;Hryniuk, William M.;Morrison, Vicki A.;Pini, T. May;Runowicz, Carolyn D.;Rosner, Gary L.;Shayne, Michelle;Sparreboom, Alex;Sucheston, Lara E.;Lyman, Gary H.

    Purpose To provide recommendations for appropriate cytotoxic chemotherapy dosing for obese adult patients with cancer.Methods The American Society of Clinical Oncology convened a Panel of experts in medical and gynecologic oncology, clinical pharmacology, pharmacokinetics and pharmacogenetics, and biostatistics and a patient representative. MEDLINE searches identified studies published in English between 1996 and 2010, and a systematic review of the literature was conducted. A majority of studies involved breast, ovarian, colon, and lung cancers. This guideline does not address dosing for novel targeted agents.Results Practice pattern studies demonstrate that up to 40% of obese patients receive limited chemotherapy doses that are not based on actual body weight. Concerns about toxicity or overdosing in obese patients with cancer, based on the use of actual body weight, are unfounded.Recommendations The Panel recommends that full weight–based cytotoxic chemotherapy doses be used to ...


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

A partir d'une revue systématique de la littérature ayant identifié 253 essais cliniques randomisés de phase III, cette étude évalue les méthodes statistiques utilisées pour estimer le bénéfice attendu des traitements

  • Assumptions of Expected Benefits in Randomized Phase III Trials Evaluating Systemic Treatments for Cancer
    Journal of the National Cancer Institute, sous presse, 2012 (résumé)
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    A partir d'une revue systématique de la littérature ayant identifié 253 essais cliniques randomisés de phase III, cette étude évalue les méthodes statistiques utilisées pour estimer le bénéfice attendu des traitements

    “Assumptions of Expected Benefits in Randomized Phase III Trials Evaluating Systemic Treatments for Cancer”

    • Gan, Hui K.;You, Benoit;Pond, Gregory R.;Chen, Eric X.

    Background In designing phase III randomized clinical trials (RCTs), the expected magnitude of the benefit of the experimental therapy (δ) determines the number of patients required and the number of person-years of follow-up. We conducted a systematic review to evaluate how reliably δ approximates the observed benefit (B) in RCTs that evaluated cancer treatment.Methods RCTs evaluating systemic therapy in adult cancer patients published in 10 journals from January 1, 2005, through December 31, 2009, were identified. Data were extracted from each publication independently by two investigators. The related-samples Sign test was used to determine whether the median difference between δ and B was statistically significant in different study subsets and was two-sided.Results A total of 253 RCTs met the eligibility criteria and were included in the analysis. Regardless of whether benefit was defined as proportional change (median difference between δ and B = −13.0%, 95% confidence ...


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

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