Menée à l'aide d'une xénogreffe orthotopique d'adénocarcinome canalaire du pancréas sur un modèle murin, cette étude évalue,du point de vue de la tolérabilité et de la réponse tumorale, l'intérêt d'une chimiothérapie de type FOLFOX délivrée localement à l'aide d'un dispositif d'ionophorèse implanté au niveau de la tumeur

Iontophoretic device delivery for the localized treatment of pancreatic ductal adenocarcinoma

Byrne, James D. ; Jajja, Mohammad R. N. ; Schorzman, Allison N. ; Keeler, Amanda W. ; Luft, J. Christopher ; Zamboni, William C. ; DeSimone, Joseph M. ; Yeh, Jen Jen

Poor delivery and systemic toxicity of many cytotoxic agents, such as the recent promising combination chemotherapy regimen of folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), restrict their full utility in the treatment of pancreatic cancer. Local delivery of chemotherapies has become possible using iontophoretic devices that are implanted directly onto pancreatic tumors. We have fabricated implantable iontophoretic devices and tested the local iontophoretic [...]

Mené sur 101 patients atteints d'un carcinome hépatocellulaire traité entre 2007 et 2012 (âge médian : 67 ans ; 77% de patients masculins), cet essai randomisé évalue, du point de vue de la réponse au traitement selon les critères RECIST 1.0 et par rapport à une embolisation utilisant des miscrosphères non chargées, l'efficacité d'une chimioembolisation transartérielle à l'aide de microsphères chargées en doxorubicine

Randomized Trial of Hepatic Artery Embolization for Hepatocellular Carcinoma Using Doxorubicin-Eluting Microspheres Compared With Embolization With Microspheres Alone

Brown, Karen T. ; Do, Richard K. ; Gonen, Mithat ; Covey, Anne M. ; Getrajdman, George I. ; Sofocleous, Constantinos T. ; Jarnagin, William R. ; D’Angelica, Michael I. ; Allen, Peter J. ; Erinjeri, Joseph P. ; Brody, Lynn A. ; O’Neill, Gerald P. ; Johnson, Kristian N. ; Garcia, Alessandra R. ; Beattie, Christopher ; Zhao, Binsheng ; Solomon, Stephen B. ; Schwartz, Lawrence H. ; DeMatteo, Ronald ; Abou-Alfa, Ghassan K.

Purpose : Transarterial chemoembolization is accepted therapy for hepatocellular carcinoma (HCC). No randomized trial has demonstrated superiority of chemoembolization compared with embolization, and the role of chemotherapy remains unclear. This randomized trial compares the outcome of embolization using microspheres alone with chemoembolization using doxorubicin-eluting microspheres. Materials and Methods : At a single tertiary referral center, patients with HCC were randomly assigned to [...]

Menée sur 24 patients atteints d'un cancer de la prostate à risque intermédiaire ou élevé de récidive (durée médiane de suivi : 25 mois), cette étude évalue la toxicité génito-urinaire et gastro-intestinale d'une radiothérapie corporelle stéréotaxique avec escalade de doses

Dose-Escalated Stereotactic Body Radiation Therapy for Patients with Intermediate and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes

Kotecha, Rupesh ; Djemil, Toufik ; Tendulkar, Rahul D. ; Reddy, Chandana A. ; Thousand, Richard A. ; Vassil, Andrew ; Stovsky, Mark ; Berglund, Ryan K. ; Klein, Eric A. ; Stephans, Kevin L.

Purpose : To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiotherapy (SBRT). Methods and Materials : Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a three mm expansion [...]

Menée à partir d'un modèle mathématique incorporant des données économiques et des résultats cliniques (toxicité, taux de complications, taux de récidive, ...), cette étude compare le rapport coût-efficacité d'une radiothérapie avec modulation d'intensité et d'une radiothérapie conformationnelle 3D dans le traitement pré-opératoire d'un sarcome des tissus mous des extrémités

Cost-Effectiveness Analysis of IMRT versus 3DCRT for Preoperative Treatment of Extremity Soft Tissue Sarcomas

Richard, Patrick ; Phillips, Mark ; Smith, Wade ; Davidson, Darin ; Kim, Edward ; Kane, Gabrielle

Purpose : Create a cost-effectiveness model comparing preoperative intensity-modulated radiation versus 3D conformal radiation for extremity soft tissue sarcomas. Methods and Materials : Input parameters included 5-year local recurrence rates, acute wound complication rates, and chronic toxicities (edema, fracture, joint stiffness, and fibrosis). Health-state utilities were used to calculate quality-adjusted life years (QALYs). Overall treatment costs per QALY or incremental cost-effectiveness [...]

Menée à partir de données portant sur 567 mastectomies partielles réalisées par 21 chirurgiens entre 2009 et 2012, cette étude identifie les facteurs et les techniques chirurgicales améliorant la qualité des marges de résection

Identifying Factors and Techniques to Decrease the Positive Margin Rate in Partial Mastectomies: Have We Missed the Mark?

Edwards, Sara B. ; Leitman, I. Michael ; Wengrofsky, Aaron J. ; Giddins, Marley J. ; Harris, Emily ; Mills, Christopher B. ; Fukuhara, Shinichi ; Cassaro, Sebastiano

Breast conservation therapy (BCT) has a reported incidence of positive margins ranging widely in the literature from 20% to 70%. Efforts have been made to refine standards for partial mastectomy and to predict which patients are at highest risk for incomplete excision. Most have focused on histology and demographics. We sought to further define modifiable risk factors for positive margins and residual disease. A retrospective study was conducted of 567 consecutive partial mastectomies by 21 [...]

Mené sur 108 patientes atteintes d'un cancer du sein de stade précoce (âge : 32 à 81 ans ; durée de suivie : 3 ans), cet essai compare les effets d'une radiothérapie conventionnelle et d'une tomothérapie hypofractionnée sur la capacité respiratoire

Mild Lung Restriction in Breast Cancer Patients after Hypofractionated and Conventional Radiotherapy : a 3-year Follow-up

Verbanck, Sylvia ; Hanon, Shane ; Schuermans, Daniel ; Van Parijs, Hilde ; Vinh-Hung, Vincent ; Miedema, Geertje ; Verellen, Dirk ; Storme, Guy ; Fontaine, Christel ; Lamote, Jan ; De Ridder, Mark ; Vincken, Walter

Purpose : Radiotherapy treatments for early stage breast cancer patients potentially affect the lung parenchyma. Previous studies have shown acute effects on the lung diffusing capacity, essentially due to lung volume restriction. We aimed to assess the effect of radiotherapy on lung function over the course of 3 years. Methods and Materials : Evolution of restrictive and obstructive lung function parameters was investigated in 108 breast cancer participants in a randomized controlled trial [...]

Menée à partir des données des registres américains des cancers et de la base Medicare portant sur 6 304 patientes atteintes d'un cancer utérin de stade I à III diagnostiqué entre 2006 et 2011, cette étude évalue, du point de vue du taux de complications, de la mortalité péri-opératoire et de la mortalité spécifique, l'intérêt d'une hystérectomie laparoscopique, assistée ou non par robot, par rapport à une hystérectomie abdominale

Comparative Effectiveness of Minimally Invasive Hysterectomy for Endometrial Cancer

Wright, Jason D. ; Burke, William M. ; Tergas, Ana I. ; Hou, June Y. ; Huang, Yongmei ; Hu, Jim C. ; Hillyer, Grace Clarke ; Ananth, Cande V. ; Neugut, Alfred I. ; Hershman, Dawn L.

Purpose : Despite the potential benefits of minimally invasive hysterectomy for uterine cancer, population-level data describing the procedure’s safety in unselected patients are lacking. We examined the use of minimally invasive surgery and the association between the route of the procedure and long-term survival. Methods : We used the SEER-Medicare database to identify women with stage I-III uterine cancer who underwent hysterectomy from 2006 to 2011. Patients who underwent abdominal [...]

Cet article passe en revue les perspectives offertes par le recours à des immunothérapies (nivolumab, pembrolizumab ou iplimumab), utilisées de façon concomitante ou séquentielle avec des thérapies ciblées, pour le traitement de patients atteints d'un mélanome ou d'une autre tumeur solide

Immunotherapy Combined or Sequenced With Targeted Therapy in the Treatment of Solid Tumors: Current Perspectives

Atkins, Michael B. ; Larkin, James

The advent of newer immunotherapeutic and molecularly targeted agents has provided a number of effective options for cancer treatment but has also added much complexity in selecting the best initial treatment or treatment plan for each patient. Molecularly targeted agents offer selectivity and are the cornerstone for “precision medicine.” While targeted agents are associated with high tumor response rates, patients inevitably develop resistance to these drugs. Immunotherapies exploit the [...]

Menée à l'aide de divers modèles murins, cette étude met en évidence des mécanismes suggérant l'intérêt d'une stratégie immunothérapeutique à base d'un agoniste de TLR5, l'entolimod, pour prévenir la formation de métastases

Toll-like receptor-5 agonist, entolimod, suppresses metastasis and induces immunity by stimulating an NK-dendritic-CD8+ T-cell axis

Brackett, Craig M. ; Kojouharov, Bojidar ; Veith, Jean ; Greene, Kellee F. ; Burdelya, Lyudmila G. ; Gollnick, Sandra O. ; Abrams, Scott I. ; Gudkov, Andrei V.

Activation of an anticancer innate immune response is highly desirable because of its inherent ability to generate an adaptive antitumor T-cell response. However, insufficient safety of innate immune modulators limits clinical use to topical applications. Toll-like receptor 5 (TLR5) agonists are favorably positioned as potential systemic immunotherapeutic agents because of unusual tissue specificity of expression, uniquely safe profile of induced cytokines, and antitumor efficacy demonstrated [...]

Cet article passe en revue les perspectives offertes par le développement de thérapies anti-angiogéniques et de biomarqueurs associés pour le traitement des patients atteints d'une tumeur solide

Antiangiogenic therapy in oncology: current status and future directions

Jayson, Gordon C. ; Kerbel, Robert ; Ellis, Lee M. ; Harris, Adrian L.

Angiogenesis, the formation of new blood vessels from pre-existing vessels, has been validated as a target in several tumour types through randomised trials, incorporating vascular endothelial growth factor (VEGF) pathway inhibitors into the therapeutic armoury. Although some tumours such as renal cell carcinoma, ovarian and cervical cancers, and pancreatic neuroendocrine tumours are sensitive to these drugs, others such as prostate cancer, pancreatic adenocarcinoma, and melanoma are resistant. [...]

Menée in vitro et in vivo sur des modèles de lymphome à cellules du manteau et de lymphome à grandes cellules B, cette étude française met en évidence des mécanismes suggérant l'intérêt d'une stratégie ciblant l'interaction entre la nétrine-1 et la protéine DCC pour le traitement des patients dont le lymphome surexprime la nétrine-1

Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas

Broutier, Laura ; Creveaux, Marion ; Vial, Jonathan ; Tortereau, Antonin ; Delcros, Jean-Guy ; Chazot, Guillaume ; McCarron, Mark J. ; Léon, Sophie ; Pangault, Celine ; Gadot, Nicolas ; Colombe, Amélie ; Boulland, Marie-Laure ; Blachier, Jonathan ; Marie, Julien C. ; Traverse-Glehen, Alexandra ; Donzé, Olivier ; Chassagne-Clément, Catherine ; Salles, Gilles ; Tarte, Karin ; Mehlen, Patrick ; Castets, Marie

DCC (Deleted in Colorectal Carcinoma) has been demonstrated to constrain tumor progression by inducing apoptosis unless engaged by its ligand netrin-1. This has been shown in breast and colorectal cancers; however, this tumor suppressive function in other cancers is not established. Using a transgenic mouse model, we report here that inhibition of DCC-induced apoptosis is associated with lymphomagenesis. In human diffuse large B-cell lymphoma (DLBCL), an imbalance of the netrin-1/DCC ratio [...]

Menée à l'aide de modèles murins, cette étude met en évidence des mécanismes suggèrant l'intérêt de combiner un inhibiteur de DDR1 et un inhibiteur de la signalisation Notch pour le traitement des patients atteints d'un adénocarcinome du poumon présentant un gène KRAS muté

Combined inhibition of DDR1 and Notch signaling is a therapeutic strategy for KRAS-driven lung adenocarcinoma

Ambrogio, Chiara ; Gómez-López, Gonzalo ; Falcone, Mattia ; Vidal, August ; Nadal, Ernest ; Crosetto, Nicola ; Blasco, Rafael B. ; Fernandez-Marcos, Pablo J. ; Sanchez-Cespedes, Montserrat ; Ren, Xiaomei ; Wang, Zhen ; Ding, Ke ; Hidalgo, Manuel ; Serrano, Manuel ; Villanueva, Alberto ; Santamaria, David ; Barbacid, Mariano

Patients with advanced Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant lung adenocarcinoma are currently treated with standard chemotherapy because of a lack of efficacious targeted therapies. We reasoned that the identification of mediators of Kras signaling in early mouse lung hyperplasias might bypass the difficulties that are imposed by intratumor heterogeneity in advanced tumors, and that it might unveil relevant therapeutic targets. Transcriptional profiling of KrasG12V-driven [...]

Menée sur des lignées cellulaires de cancer du poumon non à petites cellules, cette étude met en évidence divers mécanismes par lesquels les cellules tumorales sont susceptibles d'acquérir une résistance à un traitement par inhibiteurs d'EGFR

Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition

Hata, Aaron N. ; Niederst, Matthew J. ; Archibald, Hannah L. ; Gomez-Caraballo, Maria ; Siddiqui, Faria M. ; Mulvey, Hillary E. ; Maruvka, Yosef E. ; Ji, Fei ; Bhang, Hyo-eun C. ; Krishnamurthy Radhakrishna, Viveksagar ; Siravegna, Giulia ; Hu, Haichuan ; Raoof, Sana ; Lockerman, Elizabeth ; Kalsy, Anuj ; Lee, Dana ; Keating, Celina L. ; Ruddy, David A. ; Damon, Leah J. ; Crystal, Adam S. ; Costa, Carlotta ; Piotrowska, Zofia ; Bardelli, Alberto ; Iafrate, Anthony J. ; Sadreyev, Ruslan I. ; Stegmeier, Frank ; Getz, Gad ; Sequist, Lecia V. ; Faber, Anthony C. ; Engelman, Jeffrey A.

Although mechanisms of acquired resistance of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here we observe that acquired resistance caused by the EGFRT790M gatekeeper mutation can occur either by selection of pre-existing EGFRT790M-positive clones or via genetic evolution of initially EGFRT790M-negative drug-tolerant cells. The path to resistance impacts [...]

Menée sur des lignées cellulaires et à partir d'échantillons tumoraux et sanguins prélevés sur des patients atteints d'un cancer colorectal et inclus dans un essai clinique de phase I, cette étude suggère l'intérêt d'un anticorps oligoclonal appelé MM-151 pour surmonter une résistance au cétuximab ou au panitumumab en lien avec l'observation, dans l'ADN tumoral libre circulant, de mutations du domaine extracellulaire de EGFR

MM-151 overcomes acquired resistance to cetuximab and panitumumab in colorectal cancers harboring EGFR extracellular domain mutations

Arena, Sabrina ; Siravegna, Giulia ; Mussolin, Benedetta ; Kearns, Jeffrey D. ; Wolf, Beni B. ; Misale, Sandra ; Lazzari, Luca ; Bertotti, Andrea ; Trusolino, Livio ; Adjei, Alex A. ; Montagut, Clara ; Di Nicolantonio, Federica ; Nering, Rachel ; Bardelli, Alberto

Monoclonal antibodies against the epidermal growth factor receptor (EGFR), which drives cancer growth, are frequently used in colorectal cancer. Unfortunately, the cancers commonly develop drug-resistant mutations, and the monoclonal antibodies become ineffective. To overcome this problem, Arena et al. used an oligoclonal mixture of monoclonal antibodies called MM-151, which binds multiple parts of the EGFR molecule at once, so that the cancer cannot develop resistance by mutating one site at a [...]

Mené sur 35 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue la dose maximale tolérée et l'activité antitumorale du véliparib, un inhibiteur de PARP 1/2, en combinaison avec l'irinotecan

Phase I safety, pharmacokinetic and pharmacodynamic study of the poly (ADP-ribose) polymerase inhibitor veliparib with irinotecan in patients with advanced tumors

LoRusso, Patricia M. ; Li, Jing ; Burger, Angelika ; Heilbrun, Lance K. ; Sausville, Edward ; Boerner, Scott ; Smith, Daryn ; Pilat, Mary Jo ; Zhang, Jie ; Tolaney, Sara ; Cleary, James M. ; Chen, Alice ; Rubinstein, Lawrence ; Boerner, Julie L ; Bowditch, Adam ; Cai, Dongpo ; Bell, Tracy ; Wolanski, Andrew ; Marrero, Allison ; Zhang, Yiping ; Ji, Jiuping ; Ferry-Galow, Katherine ; Kinders, Robert ; Parchment, Ralph E ; Shapiro, Geoffrey I.

Background: Poly (ADP-ribose) polymerase (PARP) is essential for recognition and repair of DNA damage. In preclinical models, PARP inhibitors modulate topoisomerase I inhibitormediated DNA damage. This Phase I study determined the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics (PK) and pharmacodynamics (PD) of veliparib, an orally-bioavailable PARP 1/2 inhibitor, in combination with irinotecan. Methods: Patients with advanced solid tumors were treated with 100 [...]

Mené sur 95 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue la dose maximale tolérée et l'activité antitumorale du linsitinib en combinaison avec l'erlotinib

Phase I Dose Escalation Study of Linsitinib (OSI-906) and Erlotinib in Patients with Advanced Solid Tumors

Macaulay, Valentine M ; Middleton, Mark R. ; Eckhardt, S. Gail ; Rudin, Charles M. ; Juergens, Rosalyn A ; Gedrich, Richard ; Gogov, Sven ; McCarthy, Sean ; Poondru, Srinivasu ; Stephens, Andrew ; Gadgeel, Shirish M

Purpose: Cross-talk between type 1 IGF receptor (IGF-1R), insulin receptor (INSR) and epidermal growth factor receptor (EGFR) mediates resistance to individual receptor blockade. This study aimed to determine the MTD, safety, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of linsitinib, a potent oral IGF-1R/INSR inhibitor, with EGFR inhibitor erlotinib. Experimental Design: This open-label, dose-escalation study investigated linsitinib schedules S1: once-daily (QD) [...]

Cet article passe en revue les travaux récents sur l'identification et la prise en charge des effets indésirables associés aux traitements à base d'inhibiteurs des points de contrôle immunitaire

Management of Toxicities of Immune Checkpoint Inhibitors

Spain, Lavinia ; Diem, Stefan ; Larkin, James

Immune checkpoint inhibition with the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab has improved survival in metastatic melanoma, lung cancer and renal cancer. Use of these agents holds promise in other malignancies. The augmented immune response enabled by these agents has led to a particular group of side effects called immune-related adverse events (irAEs). The main irAEs include diarrhea, colitis, hepatitis, skin toxicities and endocrinopathies [...]

Mené sur 55 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue la dose maximale tolérée et l'activité antitumorale d'un traitement appelé BIND-014 à base de nanoparticules ciblant PSMA et contenant du docétaxel

Phase 1 study of PSMA-targeted docetaxel-containing nanoparticle BIND-014 in patients with advanced solid tumors

Von Hoff, Daniel ; Mita, Monica M. ; Ramanathan, Ramesh K ; Weiss, Glen J ; Mita, Alain C. ; LoRusso, Patricia M. ; Burris, Howard A. ; Hart, Lowell L ; Low, Susan C ; Parsons, Donald M ; Zale, Stephen E ; Youssoufian, Hagop ; Summa, Jason ; Sachdev, Jasgit C

Purpose: First-in-human phase 1 trial to determine the safety, pharmacokinetics, and anti-tumor activity of BIND-014, a novel, tumor PSMA-targeted nanoparticle containing docetaxel. Experimental Design: Patients with advanced solid tumors received BIND-014 every three weeks (n=28) or weekly (n=27) with dose levels ranging from 3.5 to 75 mg/m2 and 15 to 45 mg/m2, respectively. Results: BIND-014 was generally well tolerated with no unexpected toxicities. The most common drug-related toxicities [...]

Mené sur 20 patients atteints d'une leucémie myélomonocytaire chronique, cet essai multicentrique de phase I évalue la dose maximale tolérée et l'activité antitumorale du ruxolitinib, un inhibiteur de JAK1/2

A Multi-Institution Phase 1 Trial of Ruxolitinib in Patients with Chronic Myelomonocytic Leukemia (CMML)

Padron, Eric ; Dezern, Amy ; Andrade-Campos, Marcio ; Vaddi, Kris ; Scherle, Peggy ; Zhang, Qing ; Ma, Yan ; Balasis, Maria E. ; Tinsley, Sarah ; Ramadan, Hanadi ; Zimmerman, Cassandra ; Steensma, David P. ; Roboz, Gail J. ; Lancet, Jeffrey E. ; List, Alan F ; Sekeres, Mikkael A. ; Komrokji, Rami S.

Purpose: To conduct a phase 1 clinical trial exploring the safety and efficacy of ruxolitinib, a JAK1/2 inhibitor, for Chronic Myelomonocytic Leukemia (CMML). Experimental Design: Patients with CMML-1 were included without regard to previous therapy. Key exclusion criteria included an ANC<0.25x103 c/dL and a platelet count<35x103c/dL. Four cohorts were enrolled using a "rolling six" study design, with doses ranging from 5mg BID to 20mg BID of ruxolitinib in 5mg dose escalations. Results: [...]

Menée sur 28 patients atteints d'un cancer du poumon non à petites cellules traité à l'aide d'erlotinib et d'ésoméprazole (un inhibiteur de la pompe à protons), cette étude évalue l'intérêt d'ingérer une boisson à base de cola pour augmenter la biodisponibilité de l'erlotinib

Influence of the Acidic Beverage Cola on the Absorption of Erlotinib in Patients With Non–Small-Cell Lung Cancer

van Leeuwen, Roelof W.F. ; Peric, Robert ; Hussaarts, Koen G.A.M. ; Kienhuis, Emma ; IJzerman, Nikki S. ; de Bruijn, Peter ; van der Leest, Cor ; Codrington, Henk ; Kloover, Jeroen S. ; van der Holt, Bronno ; Aerts, Joachim G. ; van Gelder, Teun ; Mathijssen, Ron H.J.

Purpose Erlotinib depends on stomach pH for its bioavailability. When erlotinib is taken concurrently with a proton pump inhibitor (PPI), stomach pH increases, which results in a clinically relevant decrease of erlotinib bioavailability. We hypothesized that this drug-drug interaction is reversed by taking erlotinib with the acidic beverage cola. The effects of cola on erlotinib bioavailability in patients not treated with a PPI were also studied. Patients and Methods In this randomized, [...]

Mené sur 22 patients atteints d'un cancer métastatique de la prostate résistant à la castration, cet essai de phase 1b évalue la toxicité et l'activité antitumorale de l'enzalutamide en combinaison avec le docétaxel

Phase Ib Study of Enzalutamide in Combination with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer

Morris, Michael J. ; Rathkopf, Dana E. ; Novotny, William ; Gibbons, Jacqueline A. ; Peterson, Amy ; Khondker, Zakaria ; Ouatas, Taoufik ; Scher, Howard I. ; Fleming, Mark T

Purpose: Preclinical evidence suggests that both docetaxel and enzalutamide target androgen receptor translocation and signaling. This phase Ib study assessed the safety, tolerability, and pharmacokinetics of docetaxel when administered with enzalutamide as first-line systemic chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC). Methods: Docetaxel-naïve patients received 21 day cycles of docetaxel (75 mg/m2). Enzalutamide (160 mg/day) was administered daily starting [...]

A partir de données portant sur 443 patients atteints d'un cancer du côlon présentant une instabilité microsatellitaire, cette étude rétrospective évalue l'efficacité, du point de vue de la survie sans maladie, d'une chimiothérapie adjuvante à l'aide de fluoropyrimidine, seule ou en combinaison avec l'oxaliplatine (durée médiane de suivi : 47 mois)

Efficacy of Adjuvant Chemotherapy in Colon Cancer With Microsatellite Instability: A Large Multicenter AGEO Study

Tougeron, David ; Mouillet, Guillaume ; Trouilloud, Isabelle ; Lecomte, Thierry ; Coriat, Romain ; Aparicio, Thomas ; Des Guetz, Gaetan ; lecaille, cedric ; Artru, Pascal ; Sickersen, Gaelle ; Cauchin, Estelle ; Sefrioui, David ; Boussaha, Tarek ; Ferru, Aurélie ; Matysiak-Budnik, Tamara ; Silvain, Christine ; Karayan-Tapon, Lucie ; Pagès, Jean-Christophe ; Vernerey, Dewi ; Bonnetain, Franck ; Michel, Pierre ; Taieb, Julien ; Zaanan, Aziz

Background: Deficient mismatch repair (dMMR) colon cancer (CC) is reportedly resistant to 5-fluorouracil (5FU) adjuvant chemotherapy while preliminary data suggest chemosensitivity to oxaliplatin. We assessed the efficacy of fluoropyrimidine with and without oxaliplatin in a large cohort of dMMR CC patients. Methods: This retrospective multicenter study included all consecutive patients who underwent curative surgical resection for stage II or III dMMR CC between 2000 and 2011. Prognostic [...]

Mené sur 40 patientes atteintes d'un cancer du sein HER2+ avec métastases cérébrales, cet essai de phase II évalue l'efficacité, du point de vue d'un taux composite de réponse objective du système nerveux central, et la toxicité du nératinib

Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases

Freedman, Rachel A. ; Gelman, Rebecca S. ; Wefel, Jeffrey S. ; Melisko, Michelle E. ; Hess, Kenneth R. ; Connolly, Roisin M. ; Van Poznak, Catherine H. ; Niravath, Polly A. ; Puhalla, Shannon L. ; Ibrahim, Nuhad ; Blackwell, Kimberly L. ; Liu, Minetta C. ; Lowe, Alarice ; Agar, Nathalie Y.R. ; Ryabin, Nicole ; Farooq, Sarah ; Lawler, Elizabeth ; Rimawi, Mothaffar F. ; Krop, Ian E. ; Wolff, Antonio C. ; Winer, Eric P. ; Lin, Nancy U.

Purpose Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)–positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. Patients and Methods [...]

Mené sur 2 098 patientes atteintes d'un cancer métastatique du sein, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'époétine alpha en traitement d'une anémie pendant la chimiothérapie

A Randomized, Open-Label, Multicenter, Phase III Study of Epoetin Alfa Versus Best Standard of Care in Anemic Patients With Metastatic Breast Cancer Receiving Standard Chemotherapy

Leyland-Jones, Brian ; Bondarenko, Igor ; Nemsadze, Gia ; Smirnov, Vitaliy ; Litvin, Iryna ; Kokhreidze, Irakli ; Abshilava, Lia ; Janjalia, Mikheil ; Li, Rubi ; Lakshmaiah, Kuntegowda C. ; Samkharadze, Beka ; Tarasova, Oksana ; Mohapatra, Ranjan Kumar ; Sparyk, Yaroslav ; Polenkov, Sergey ; Vladimirov, Vladimir ; Xiu, Liang ; Zhu, Eugene ; Kimelblatt, Bruce ; Deprince, Kris ; Safonov, Ilya ; Bowers, Peter ; Vercammen, Els

Purpose An open-label, noninferiority study to evaluate the impact of epoetin alfa (EPO) on tumor outcomes when used to treat anemia in patients receiving chemotherapy for metastatic breast cancer. Methods Women with hemoglobin ≤ 11.0 g/dL, receiving first- or second-line chemotherapy for metastatic breast cancer, were randomly assigned to EPO 40,000 IU subcutaneously once a week or best standard of care. The primary end point was progression-free survival (PFS). Secondary end points included [...]

A partir d'une revue de la littérature publiée depuis 15 ans, cette étude met en évidence un taux plus élevé d'événements indésirables associés au sorafénib chez les patients atteints d'un carcinome différencié de la thyroïde, par rapport aux patients atteints d'un carcinome hépatocellulaire ou rénal

Toxic effects of sorafenib in patients with differentiated thyroid carcinoma compared with other cancers

Jean, G. W. ; Mani, R. M. ; Jaffry, A. ; Khan, S. A.

Importance  Sorafenib is approved by the US Food and Drug Administration for metastatic, radioactive iodine–refractory differentiated thyroid cancer. However, adverse effects common to the tyrosine kinase inhibitor class occur at a noticeably higher rate with sorafenib use in thyroid cancer patients. The mechanism for this increase in toxic effects is unknown. Objective  To provide an overview of the adverse effect profile of sorafenib in differentiated thyroid cancer and summarizes the [...]

Menée in vitro et à l'aide d'un modèle murin, cette étude montre qu'une immunophotothérapie, utilisant le trastuzumab conjugué à la phtalocyanine IRDye 700DX ainsi qu'un adénovirus modifié exprimant le domaine extracellulaire du récepteur HER2, peut inhiber les métastases péritonéales ayant pour origine une tumeur de l'estomac HER2-

Trastuzumab-based photoimmunotherapy integrated with viral HER2 transduction inhibits peritoneally disseminated HER2-negative cancer

Ishida, Michihiro ; Kagawa, Shunsuke ; Shimoyama, Kyoko ; Takehara, Kiyoto ; Noma, Kazuhiro ; Tanabe, Shunsuke ; Shirakawa, Yasuhiro ; Tazawa, Hiroshi ; Kobayashi, Hisataka ; Fujiwara, Toshiyoshi

Peritoneal dissemination is the most frequent metastasis in gastric cancer and is associated with poor prognosis. The lack of particular target antigens in gastric cancer other than human epidermal growth factor receptor 2 (HER2) has hampered the development of treatments for peritoneal dissemination of gastric cancer. We hypothesized that HER2-extracellular domain (HER2-ECD) gene transduction combined with trastuzumab-based photoimmunotherapy (PIT) might provide excellent and selective [...]

Mené sur 774 patients atteints d'un mélanome cutané primitif et ayant subi une biopsie du ganglion sentinelle (âge : 18 à 70 ans ; profondeur du mélanome : supérieure ou égale à 1 mm ; durée médiane de suivi : 71 mois), cet essai multicentrique de phase III évalue, du point de vue de la survie sans maladie et de la survie globale, l'intérêt d'un curage ganglionnaire complet en combinaison ou non avec une forte dose d'interféron alpha-2b après la résection du mélanome

Final Results of the Sunbelt Melanoma Trial: A Multi-Institutional Prospective Randomized Phase III Study Evaluating the Role of Adjuvant High-Dose Interferon Alfa-2b and Completion Lymph Node Dissection for Patients Staged by Sentinel Lymph Node Biopsy

McMasters, Kelly M. ; Egger, Michael E. ; Edwards, Michael J. ; Ross, Merrick I. ; Reintgen, Douglas S. ; Noyes, R. Dirk ; Martin, Robert C.G. ; Goydos, James S. ; Beitsch, Peter D. ; Urist, Marshall M. ; Ariyan, Stephan ; Sussman, Jeffrey J. ; Davidson, B. Scott ; Gershenwald, Jeffrey E. ; Hagendoorn, Lee J. ; Stromberg, Arnold J. ; Scoggins, Charles R.

Purpose : The Sunbelt Melanoma Trial is a prospective randomized trial evaluating the role of high-dose interferon alfa-2b therapy (HDI) or completion lymph node dissection (CLND) for patients with melanoma staged by sentinel lymph node (SLN) biopsy. Patients and Methods : Patients were eligible if they were age 18 to 70 years with primary cutaneous melanoma ≥ 1.0 mm Breslow thickness and underwent SLN biopsy. In Protocol A, patients with a single tumor-positive lymph node after SLN biopsy [...]

Menée in vitro et à l'aide d'une xénogreffe de cancer du poumon non à petites cellules, cette étude évalue les effets combinés de l'acide subéroylanilide hydroxamique et du cisplatine sur la radiosensibilité des cellules tumorales et leurs capacités invasives

Combined Effects of Suberoylanilide Hydroxamic Acid and Cisplatin on Radiation Sensitivity and Cancer Cell Invasion in Non-small-cell Lung Cancer

Feng, Jianguo ; Zhang, Shirong ; Wu, Kan ; Wang, Bing ; Wong, Jeffrey YC ; Jiang, Hong ; Xu, Rujun ; Ying, Lisha ; Huang, Haixiu ; Zheng, Xiaoliang ; Chen, Xufeng ; Ma, Shenglin

Lung cancer is a leading cause of cancer mortality worldwide, and concurrent chemoradiotherapy has been explored as a therapeutic option. However, the chemotherapeutic agents cannot be administered for most patients at full doses safely with radical doses of thoracic radiation, and further optimizations of chemotherapy regimen to be given with radiation are needed. In this study, we examined the effects of suberoylanilide hydroxamic acid (SAHA) and cisplatin on DNA damage repairs, and [...]

Menée in vitro et à l'aide de xénogreffes de cancer de la prostate, cette étude montre qu'un traitement anti-androgénique suivi d'une courte stimulation androgénique sensibilise de manière sélective aux rayonnements ionisants les cellules tumorales exprimant le récepteur androgénique

Androgen deprivation followed by acute androgen stimulation selectively sensitizes AR-positive prostate cancer cells to ionizing radiation

Hedayati, Mohammad ; Haffner, Michael C. ; Coulter, Jonathan ; Raval, Raju R ; Zhang, Yonggang ; Zhou, Haoming ; Mian, Omar ; Knight, Emma J ; Dalrymple, Susan ; Isaacs, John T ; Santos, Aileen ; Hales, Russell K. ; Razavi, Nina ; Nelson, William G. ; Yegnasubramanian, Srinivasan ; DeWEese, Theodore L

Purpose : The current standard of care for patients with locally advanced prostate cancer is a combination of androgen deprivation and radiation therapy. Radiation is typically given with androgen suppression when testosterone levels are at their nadir. Recent reports have shown that androgen stimulation of androgen deprived prostate cancer cells leads to formation of double strand breaks (DSBs). Here, we exploit this finding and investigate the extent and timing of androgen induced DSBs and [...]

Menée à partir des données du registre national américain des cancers portant sur 15 315 patientes atteintes d'un cancer du sein de stade cT1-3 cN1 M0 et ayant reçu une chimiothérapie néoadjuvante, cette étude évalue, du point de vue de la survie globale, l'intérêt d'une radiothérapie après mastectomie et d'une irradiation des ganglions régionaux après traitement chirurgical conservateur

The Impact of Postmastectomy and Regional Nodal Radiation after Neoadjuvant Chemotherapy for Clinically Lymph Node Positive Breast Cancer: A National Cancer Database (NCDB) Analysis

Rusthoven, C.G. ; Rabinovitch, R.A. ; Jones, B.L ; Koshy, M. ; Amini, A. ; Yeh, N. ; Jackson, M.W. ; Fisher, C.M.

Background : Following neoadjuvant chemotherapy (NAC), the optimal strategies for postmastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after breast-conserving surgery (BCS) are controversial. In this analysis, we evaluate the impact of these radiotherapy approaches for women with clinically node-positive breast cancer treated with NAC in the National Cancer Database (NCDB). Patients and Methods : Women with cT1-3 cN1 M0 breast cancer treated with NAC were divided into four [...]

Menée à partir de données portant sur 193 patients présentant des métastases cérébrales traitées entre 2009 et 2014 (âge médian : 61 ans), cette étude évalue, du point de vue de la toxicité et de la survie, l'intérêt d'un traitement systémique en combinaison avec une radiochirurgie stéréotaxique concomitante

Stereotactic radiosurgery: Treatment of brain metastasis without interruption of systemic therapy

Shen, Colette J. ; Kummerlowe, Megan N. ; Redmond, Kristin J. ; Lim, Michael K. ; Rigamonti, Daniele ; Kleinberg, Lawrence R.

Purpose/Objective : Systemic therapy is typically not given concurrently with whole brain radiation therapy (WBRT) for treatment of metastatic disease due to increased risk of myelosuppression and neurotoxicity. The goal of this study was to evaluate the prevalence, outcomes, and toxicities of concurrent delivery of systemic therapy with stereotactic radiosurgery (SRS) for treatment of brain metastases. Materials/Methods : We conducted a retrospective review of 193 patients treated at our [...]

Cet article décrit, du point de vue de l'American Society of Clinical Oncology, les principaux progrès dans la recherche clinique sur les cancers en 2015

Clinical Cancer Advances 2016: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology

Dizon, Don S. ; Krilov, Lada ; Cohen, Ezra ; Gangadhar, Tara ; Ganz, Patricia A. ; Hensing, Thomas A. ; Hunger, Stephen ; Krishnamurthi, Smitha S. ; Lassman, Andrew B. ; Markham, Merry Jennifer ; Mayer, Erica ; Neuss, Michael ; Pal, Sumanta Kumar ; Richardson, Lisa C. ; Schilsky, Richard ; Schwartz, Gary K. ; Spriggs, David R. ; Villalona-Calero, Miguel Angel ; Villani, Gina ; Masters, Gregory

In 2015, approximately 1.7 million Americans received a cancer diagnosis.1 In 2030, this number will rise to nearly 2.3 million.2 Today, approximately two of three Americans will live at least 5 years after being diagnosed with an invasive cancer.3 In addition, with care that aims to balance effectiveness of treatment alongside the importance of quality of life, more patients than ever are not just living longer but able to lead full lives. Yet, cancer remains a leading cause of death in the [...]

A partir d'une revue systématique de la littérature (18 articles), cette étude analyse le rapport coût-efficacité de la protonthérapie

A systematic review of the cost and cost-effectiveness studies of proton radiotherapy

Verma, Vivek ; Mishra, Mark V. ; Mehta, Minesh P.

BACKGROUND : Economic analyses of new technologies, such as proton-beam radiotherapy (PBT), are a public health priority. To date, no systematic review of the cost-effectiveness of PBT has been performed. METHODS : Systematic searches of PubMed, EMBASE, abstracts from American Society for Radiation Oncology and American Society of Clinical Oncology meetings, and the Cost-Effectiveness Analysis Registry were conducted (2000-2015) along with abstracts from the Particle Therapy Co-Operative Group [...]

A partir d'une revue de la littérature (10 essais randomisés identifiés, 3 043 patients), cette étude évalue le risque d'occlusion vasculaire associée à un traitement par dasatinib, nilotinib ou ponatinib

Association between BCR-ABL tyrosine kinase inhibitors for chronic myeloid leukemia and cardiovascular events, major molecular response, and overall survival: A systematic review and meta-analysis

Douxfils, J. ; Haguet, H. ; Mullier, F. ; Chatelain, C. ; Graux, C. ; Dogné, J.

Importance  A phase 3 trial with ponatinib in patients with chronic myeloid leukemia (CML) was interrupted due to an important increase of vascular occlusive events. A similar risk was also suspected with nilotinib, another BCR-ABL tyrosine kinase inhibitor (TKI) used in patients with CML. Objective  To assess the risk of vascular occlusive events in patients with CML treated by new generations of TKIs and provide an overall assessment of the clinical benefit. Data Sources  Two independent [...]

Cet article passe en revue l'histoire récente du développement des recommandations en matière de détection de problèmes cardiaques chez les patientes traitées à l'aide de trastuzumab pour un cancer du sein, puis analyse la controverse sur l'évaluation des bénéfices des diverses stratégies de détection et d'intervention

Cardiac Surveillance Guidelines for Trastuzumab-Containing Therapy in Early-Stage Breast Cancer: Getting to the Heart of the Matter

Dang, Chau T. ; Yu, Anthony F. ; Jones, Lee W. ; Liu, Jennifer ; Steingart, Richard M. ; Argolo, Daniel F. ; Norton, Larry ; Hudis, Clifford A.

Trastuzumab-containing regimens for breast cancer have significantly improved survival both in the early-stage and metastatic settings.1-8 Nevertheless, given the early signals of cardiotoxicity, a prevailing concern exists regarding the risk of cardiotoxicity, defined as a decline in left ventricular ejection fraction (LVEF) both asymptomatic and symptomatic. This concern that LVEF decline would be an early and actionable surrogate for subsequent development of congestive heart failure (CHF) [...]

Menée en France à partir de données portant sur 173 patients atteints d'un cancer de la tête et du cou traité entre 2010 et 2012, cette étude compare les coûts associés à deux techniques de radiothérapie : l'arcthérapie volumétrique avec modulation d'intensité et la tomothérapie

A cost analysis of complex radiotherapy for patients with head and neck cancer

Perrier, Lionel ; Morelle, Magali ; Pommier, Pascal ; Boisselier, Pierre ; Coche-Dequeant, Bernard ; Gallocher, Olivier ; Alfonsi, Marc ; Bardet, Etienne ; Rives, Michel ; Calugaru, Valentin ; Chajon, Enrique ; Noël, Georges ; Mecellem, Hinda ; Pérol, David ; Dussart, Sophie ; Giraud, Prof Philippe

Purpose : This cost analysis aimed to prospectively assess the difference in costs between TomoTherapy® and Volumetric-modulated Arc Therapy (VMAT) in patients with head and neck cancer. Materials and methods : Economic data were gathered from a multicenter study. However, randomization was not possible due to the availability of equipment. Costs were calculated using the micro-costing technique from the hospital’s perspective (in Euros, 2013) and the time horizon was radiation therapy. Only [...]