Menée in vitro et à l'aide de modèles murins, cette étude suggère que des modifications du micro-environnement tumoral consécutives à une intervention chirurgicale expliqueraient la résistance des tumeurs à une immunothérapie

Changes in the local tumor microenvironment in recurrent cancers may explain the failure of vaccines after surgery

Predina, Jarrod ; Eruslanov, Evgeniy ; Judy, Brendan ; Kapoor, Veena ; Cheng, Guanjun ; Wang, Liang-Chuan ; Sun, Jing ; Moon, Edmund K. ; Fridlender, Zvi Gregorio ; Albelda, Steven ; Singhal, Sunil

Each year, more than 700,000 people undergo cancer surgery in the United States. However, more than 40% of those patients develop recurrences and have a poor outcome. Traditionally, the medical community has assumed that recurrent tumors arise from selected tumor clones that are refractory to therapy. However, we found that tumor cells have few phenotypical differences after surgery. Thus, we propose an alternative explanation for the resistance of recurrent tumors. Surgery promotes inhibitory [...]

Menée sur 718 patients atteints d'un cancer de la prostate traité par radiothérapie externe, cette étude montre une association entre l'âge des patients, la présence de comorbidités et le risque de toxicité rectale à long terme

Age and Comorbid Illness Are Associated With Late Rectal Toxicity Following Dose-Escalated Radiation Therapy for Prostate Cancer

Hamstra, Daniel A. ; Stenmark, Matt ; Ritter, Tim ; Litzenberg, Dale ; Jackson, William ; Johnson, Skyler ; Albrecht-Unger, Liesel ; Donaghy, Alex ; Phelps, Laura ; Blas, Kevin ; Halverson, Schuyler ; Marsh, Robin ; Olson, Karin ; Feng, Felix Y.

To assess the impacts of patient age and comorbid illness on rectal toxicity following external beam radiation therapy (EBRT) for prostate cancer and to assess the Qualitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) normal tissue complication probability (NTCP) model in this context. Rectal toxicity was analyzed in 718 men previously treated for prostate cancer with EBRT (≥75 Gy). Comorbid illness was scored using the Charlson Comorbidity Index (CCMI), and the NTCP was [...]

Menée sur 106 patients atteints d'un cancer localisé de la prostate traité entre 2009 et 2011 (âge médian : 66,5 ans), cette étude évalue la morbidité associée à différents traitements localisés (ultrasons focalisés de haute intensité, curiethérapie, cryothérapie et thérapie photodynamique vasculaire)

Morbidity of Focal Therapy in the Treatment of Localized Prostate Cancer

Eric, Barret ; Youness, Ahallal ; Rafael, Sanchez-Salas ; Marc, Galiano ; Jean-Marc, Cosset ; Pierre, Validire ; Petr, Macek ; Matthieu, Durand ; Dominique, Prapotnich ; François, Rozet ; Xavier, Cathelineau

Background : Focal therapy (FT) for prostate cancer (PCa) seems to be part of a natural evolution in the quest to improve the management of early organ-confined disease. Objective : To assess the morbidity of the initial experience of FT in a tertiary referral center for PCa management. Design, setting, and participants : From 2009 to 2011, a total of 1213 patients with clinically localized PCa were treated at our institution. Of these patients, 547 were considered to have indolent disease [...]

Menée en France sur 265 patients atteints d'un carcinome à cellules rénales traité entre 2007 et 2011 (durée médiane de suivi : 7 ou 18 mois), cette étude prospective multicentrique compare, en fonction des caractéristiques anatomiques de la tumeur et du point de vue de données opératoires (perte de sang, durée de l'opération, temps d'ischémie chaude) et post-opératoires (durée du séjour, taux de complications), deux techniques de néphrectomie partielle (laparoscopie pure ou assistée par robot)

A prospective comparison of surgical and pathological outcomes obtained after robot-assisted or pure laparoscopic partial nephrectomy in moderate to complex renal tumours: results from a French multicentre collaborative study

Masson-Lecomte, Alexandra ; Bensalah, Karim ; Seringe, Elise ; Vaessen, Christophe ; de la Taille, Alexandre ; Doumerc, Nicolas ; Rischmann, Pascal ; Bruyère, Franck ; Soustelle, Laurent ; Droupy, Stéphane ; Rouprêt, Morgan

What's known on the subject? and What does the study add? * Nephron-sparing surgery has become the standard of care for small renal masses because it allows for the same oncological control as radical nephrectomy and achieves better overall survival, while lowering the risk of subsequent chronic renal failure. * Mini-invasive surgical approaches have also been developed, e.g. laparoscopic partial nephrectomy (LPN) and robot-assisted laparoscopic PN (RAPN), which result in less bleeding, reduced [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude évalue l'activité antitumorale de la combinaison du sorafenib et du cisplatine pour le traitement d'un hépatoblastome à haut risque ou récidivant

Effect of sorafenib combined with cytostatic agents on hepatoblastoma cell lines and xenografts

Eicher, C. ; Dewerth, A. ; Thomale, J. ; Ellerkamp, V. ; Hildenbrand, S. ; Warmann, S. W. ; Fuchs, J. ; Armeanu-Ebinger, S.

Background: Sorafenib has recently been shown to reduce tumour growth in hepatoblastoma (HB) xenografts. The effect of a combined administration with cytostatic agents was now investigated. Methods: Cell viability after treatment with sorafenib and different cytostatic agents was evaluated in two HB cell lines (HUH6 and HepT1) using MTT assay. ERK signalling was investigated by western blot, NOXA expression by rt-PCR, and formation of DNA adducts using immunocytology. NMRI mice bearing [...]

Cet article passe en revue les perspectives offertes par la manipulation des lymphocytes T régulateurs pour le développement de traitements anticancéreux

Therapeutic opportunities for manipulating TReg cells in autoimmunity and cancer

von Boehmer, Harald ; Daniel, Carolin

Forkhead box P3 (FOXP3)-expressing regulatory T (TReg) cells have a pivotal role in the regulation of immune responses and in the maintenance of immunological self-tolerance. These cells have emerged as attractive targets for strategies that allow the steering of immune responses in desired directions — arming the immune system to destroy infected cells and cancer cells or downregulating it to limit tissue destruction in autoimmunity. Efforts to understand the generation, activation and [...]

Menée à l'aide de modèles murins, cette étude évalue l'activité antitumorale d'un composé appelé SCR7, un inhibiteur de l'ADN ligase IV, seul ou en combinaison avec divers agents de chimiothérapie

An Inhibitor of Nonhomologous End-Joining Abrogates Double-Strand Break Repair and Impedes Cancer Progression

Srivastava, Mrinal ; Nambiar, Mridula ; Sharma, Sheetal ; Karki, Subhas S ; Goldsmith, G. ; Hegde, Mahesh ; Kumar, Sujeet ; Pandey, Monica ; Singh, Ram K ; Ray, Pritha ; Natarajan, Renuka ; Kelkar, Madhura ; De, Abhijit ; Choudhary, Bibha ; Raghavan, Sathees C

DNA Ligase IV is responsible for sealing of double-strand breaks (DSBs) during nonhomologous end-joining (NHEJ). Inhibiting Ligase IV could result in amassing of DSBs, thereby serving as a strategy toward treatment of cancer. Here, we identify a molecule, SCR7 that inhibits joining of DSBs in cell-free repair system. SCR7 blocks Ligase IV-mediated joining by interfering with its DNA binding but not that of T4 DNA Ligase or Ligase I. SCR7 inhibits NHEJ in a Ligase IV-dependent manner within [...]

Menée in vitro et à l'aide de xénogreffes, cette étude met en évidence un mécanisme, l'inhibition d'une voie de signalisation liée à la réponse inflammatoire, permettant de rendre compte de l'activité anticancéreuse d'un antidiabétique, la metformine

Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth

Hirsch, Heather A. ; Iliopoulos, Dimitrios ; Struhl, Kevin

Metformin, the first-line drug for treating diabetes, inhibits cellular transformation and selectively kills cancer stem cells in breast cancer cell lines. In a Src-inducible model of cellular transformation, metformin inhibits the earliest known step in the process, activation of the inflammatory transcription factor NF-κB. Metformin strongly delays cellular transformation in a manner similar to that occurring upon a weaker inflammatory stimulus. Conversely, inhibition of transformation does [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes de divers types de cancer, cette étude évalue l'activité antitumorale d'un composé appelé VS-5584, un inhibiteur de la signalisation PI3K/mTOR

VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer

Hart, Stefan ; Novotny-Diermayr, Veronica ; Goh, Kee Chuan ; Williams, Meredith ; Tan, Yong Cheng ; Ong, Lai Chun ; Cheong, Albert ; Ng, Bee Kheng ; Amalini, Chithra ; Madan, Babita ; Nagaraj, Harish ; Jayaraman, Ramesh ; Pasha, Khalis M ; Ethirajulu, Kantharaj ; Chng, Wee Joo ; Mustafa, Nurulhuda ; Goh, Boon Cher ; Benes, Cyril H. ; McDermott, Ultan ; Garnett, Mathew J. ; Dymock, Brian ; Wood, Jeanette M

Dysregulation of the PI3K/mTOR pathway either through amplifications, deletions or as a direct result of mutations, has been closely linked to the development and progression of a wide range of cancers. Moreover, this pathway activation is a poor prognostic marker for many tumor types and confers resistance to various cancer therapies. Here we describe VS-5584, a novel, low molecular-weight compound with equivalent potent activity against mTOR (IC50 = 37 nM) and all class I PI3K isoforms IC50: [...]

Cet article passe en revue les enjeux associés au développement d'inhibiteurs de la famille des enzymes PARP pour le traitement des cancers

Molecular Pathways: Targeting PARP in Cancer Treatment

Do, Khanh ; Chen, Alice

Poly (ADP-ribose) polymerases (PARPs) are a family of nuclear protein enzymes involved in the DNA damage response. The role of PARP-1 in base excisional repair has been extensively characterized. More recent in vitro studies additionally implicate a role for PARP-1 in facilitating homologous recombination and non-homologous end-joining. The more faithful process of homologous recombination repair of double-stranded DNA breaks, involves localization of BRCA-1 and BRCA-2 to sites of DNA damage, [...]

Cet article passe en revue les perspectives offertes par la voie de signalisation WNT pour le développement de thérapies ciblées des cancers

WNT signalling pathways as therapeutic targets in cancer

Anastas, Jamie N. ; Moon, Randall T.

Since the initial discovery of the oncogenic activity of WNT1 in mouse mammary glands, our appreciation for the complex roles for WNT signalling pathways in cancer has increased dramatically. WNTs and their downstream effectors regulate various processes that are important for cancer progression, including tumour initiation, tumour growth, cell senescence, cell death, differentiation and metastasis. Although WNT signalling pathways have been difficult to target, improved drug-discovery [...]

Menée in vitro et à l'aide de xénogreffes, cette étude évalue les effets du parthénolide sur les cellules souches de leucémies pédiatriques

Parthenolide eliminates leukemia initiating cell populations and improves survival in xenografts of childhood acute lymphoblastic leukemia

Diamanti, Paraskevi ; Cox, Charlotte V. ; Moppett, John P. ; Blair, Allison

Around 20% of children with acute lymphoblastic leukemia (ALL) relapse due to failure to eradicate the disease. Current drug efficacy studies focus on reducing leukemia cell burden. However, if drugs have limited effects on leukemia-initiating cells (LIC), these cells may expand and eventually cause relapse. Parthenolide (PTL) has been shown to cause apoptosis of LIC in acute myeloid leukemia. Here, we assessed the effects of PTL on LIC populations in childhood ALL. Apoptosis assays [...]

Cet article passe en revue les perspectives thérapeutiques offertes par les travaux récents sur les mécanismes cellulaires du cancer de la prostate résistant à la castration

Adaptation or selection-mechanisms of castration-resistant prostate cancer

Zong, Yang ; Goldstein, Andrew S.

Men with advanced prostate cancer are typically treated with hormonal therapy, which leads to tumour shrinkage. However, tumours relapse and develop into the lethal form of the disease, termed castration-resistant prostate cancer (CRPC). Two distinct, but not mutually exclusive, models have been proposed in the literature to describe the onset of CRPC: adaptation and selection. Although some studies indicate that tumour cells acquire new alterations that enable them to survive in the castrated [...]

Menée in vitro et in vivo, cette étude met en évidence un mécanisme, lié à l'activation de la signalisation PI3K/AKT, permettant de rendre compte de la résistance au vemurafenib dans les cancers colorectaux présentant la mutation V600E du gène BRAF

Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents

Mao, Muling ; Tian, Feng ; Mariadason, John M. ; Tsao, Lawrence ; Lemos, Robert ; Dayyani, Farshid ; Yennu Nanda, Vashisht Gopal ; Jiang, Zhi-Qin ; Wistuba, Ignacio ; Tang, Ximing ; Bornmann, William G. ; Bollag, Gideon ; Mills, Gordon B. ; Powis, Garth ; Desai, Jayesh ; Gallick, Gary E. ; Davies, Michael A. ; Kopetz, Scott

Purpose: Vemurafenib, a selective inhibitor of BRAFV600 has shown significant activity in BRAFV600 melanoma, but not in the <10% of metastatic BRAFV600 colorectal cancers (CRC), suggesting that studies of the unique hypermethylated phenotype and concurrent oncogenic activation of BRAFmut CRC may provide combinatorial strategies Experimental Design: We performed comparative proteomic analysis of BRAFV600E melanoma and CRC cell lines, followed by correlation of PI3K pathway activation and [...]

Menée à l'aide de xénogreffes de tumeurs du sein triplement négatives, cette étude évalue l'activité antitumorale d'un composé appelé E-3810, un inhibiteur de l'activité tyrosine kinase des récepteurs VEGFR-1, -2, -3 et FGFR-1

The tyrosine kinase inhibitor E-3810 combined with paclitaxel inhibits the growth of advanced- stage triple-negative breast cancer xenografts

Bello, Ezia ; Taraboletti, Giulia ; Colella, Gennaro ; Zucchetti, Massimo ; Forestieri, Daniele ; Licandro, Simonetta Andrea ; Berndt, Alexander ; Richter, Petra ; D'Incalci, Maurizio ; Cavalletti, Ennio ; Giavazzi, Raffaella ; Camboni, Gabriella ; Damia, Giovanna

E-3810 is a novel small molecule that inhibits VEGFR-1, -2 and -3 and FGFR-1 tyrosine kinases at nM concentrations currently in Phase clinical II. In preclinical studies it had a broad spectrum of antitumor activity when used as monotherapy in a variety of human xenografts. We here investigated the activity of E-3810 combined with different cytotoxic agents in a MDA-MB-231 triple-negative breast cancer xenograft model. The molecule could be safely administered with 5-fluorouracil, cisplatin and [...]

Menée in vitro et in vivo, cette étude évalue l'effet d'un composé appelé LLP-3 sur les cellules souches de glioblastome multiforme

Impairment of glioma stem cell survival and growth by a novel inhibitor for Survivin/Ran protein complex

Guvenc, Hacer ; Pavlyukov, Marat S. ; Kurt, Habibe ; Joshi, Kaushal ; Banasavadi-Siddegowda, Yeshavanth K. ; Mao, Ping ; Hong, Christopher ; Yamada, Ryosuke ; Kwon, Chang-Hyuk ; Bhasin, Deepak ; Chettiar, Somsundaram N. ; Kitange, Gaspar J. ; Park, In-Hee ; Sarkaria, Jann N. ; Li, Chenglong ; Shakhparonov, Mihail I. ; Nakano, Ichiro

Purpose:Glioblastoma multiforme (GBM) is a devastating disease. Recent studies suggest that the stem cell properties of GBM contribute to the development of therapy resistance. Experimental Design:The expression of Survivin and Ran was evaluated by immunohistochemistry with GBM tissues, and qRT-PCR and immunocytochemistry with patient-derived GBM sphere cultures. With computational structure-based drug design, 11 small-molecule compounds were designed, synthesized, and evaluated as inhibitor [...]

Mené sur 96 patients atteints d'un carcinome hépatocellulaire non résécable, cet essai japonais identifie les caractéristiques cliniques associées à l'arrêt d'un traitement par sorafenib en raison d'effets indésirables sévères

Clinical factors related to long-term administration of sorafenib in patients with hepatocellular carcinoma

Nojiri S, ; Kusakabe A, ; Fujiwara K, ; Shinkai N, ; Matsuura K, ; Iio E, ; Miyaki T, ; Nomura T, ; Sobue S, ; Sano H, ; Hasegawa I, ; Ohno T, ; Takahashi Y, ; Orito E, ; Joh T

Background: Sorafenib has been approved in the indication of unresectable hepatocellular carcinoma, but there are many cases in which administration of the drug is discontinued due to severe side effects. In this study, we compared the characteristics of patients who continued and discontinued sorafenib. Methods: Ninety-six patients (75 men and 21 women) were initiated on sorafenib from July 2009 through September 2011. The patient characteristics of interest included gender, age, etiology, [...]

Menée sur 727 patients atteints d'une leucémie myéloïde aiguë (âge médian : 67 ans), cette étude française identifie des facteurs prédictifs de la réponse à une chimiothérapie par idarubicine ou daunorubicine

Superior Long-Term Outcome With Idarubicin Compared With High-Dose Daunorubicin in Patients With Acute Myeloid Leukemia Age 50 Years and Older

Gardin, Claude ; Chevret, Sylvie ; Pautas, Cécile ; Turlure, Pascal ; Raffoux, Emmanuel ; Thomas, Xavier ; Quesnel, Bruno ; de Revel, Thierry ; de Botton, Stéphane ; Gachard, Nathalie ; Renneville, Aline ; Boissel, Nicolas ; Preudhomme, Claude ; Terré, Christine ; Fenaux, Pierre ; Bordessoule, Dominique ; Celli-Lebras, Karine ; Castaigne, Sylvie ; Dombret, Hervé

Purpose Although standard chemotherapy remains associated with a poor outcome in older patients with acute myeloid leukemia (AML), it is unclear which patients can survive long enough to be considered as cured. This study aimed to identify factors influencing the long-term outcome in these patients. Patients and Methods The study included 727 older patients with AML (median age, 67 years) treated in two idarubicin (IDA) versus daunorubicin (DNR) Acute Leukemia French Association trials. [...]

Mené sur 59 patients atteints d'une leucémie lymphocytaire chronique récidivante ou réfractaire, cet essai de phase II évalue, du point de vue du taux de réponse globale, un traitement combinant lénalidomide et rituximab

Phase II Study of Lenalidomide and Rituximab As Salvage Therapy for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

Badoux, Xavier C. ; Keating, Michael J. ; Wen, Sijin ; Wierda, William G. ; O'Brien, Susan M. ; Faderl, Stefan ; Sargent, Rachel ; Burger, Jan A. ; Ferrajoli, Alessandra

Purpose Lenalidomide is an immunomodulatory drug active as salvage therapy for chronic lymphocytic leukemia (CLL). We combined lenalidomide with rituximab to improve response rates in patients with relapsed or refractory CLL. Patients and Methods Fifty-nine adult patients (age 42 to 82 years) with relapsed or refractory CLL were enrolled onto a phase II study of lenalidomide and rituximab. Patients had received prior fludarabine-based therapy or chemoimmunotherapy. Rituximab (375 mg/m2 [...]

Mené sur 36 patients atteints d'un lymphome hodgkinien récidivant et réfractaire, cet essai de phase II évalue, du point de vue du taux de réponse globale, un traitement par bendamustine

Phase II Study of Bendamustine in Relapsed and Refractory Hodgkin Lymphoma

Moskowitz, Alison J. ; Hamlin, Paul A. ; Perales, Miguel-Angel ; Gerecitano, John ; Horwitz, Steven M. ; Matasar, Matthew J. ; Noy, Ariela ; Palomba, Maria Lia ; Portlock, Carol S. ; Straus, David J. ; Graustein, Tricia ; Zelenetz, Andrew D. ; Moskowitz, Craig H.

Purpose Limited data exist regarding the activity of bendamustine in Hodgkin lymphoma (HL). This phase II study evaluated the efficacy of bendamustine in relapsed and refractory HL. Patients and Methods Patients with relapsed and refractory HL who were ineligible for autologous stem-cell transplantation (ASCT), or for whom this treatment failed, received bendamustine 120 mg/m2 as a 30-minute infusion on days 1 and 2 every 28 days with growth factor support. The primary end point was overall [...]

Cet article passe en revue les travaux récents sur les toxicités cutanées associées aux inhibiteurs de BRAF pour le traitement d'un mélanome métastatique

Cutaneous toxicities of RAF inhibitors

Anforth, Rachael ; Fernandez-Peñas, Pablo ; Long, Georgina V.

The RAF inhibitors vemurafenib and dabrafenib are emerging as the standard of care for Val600BRAF-mutant metastatic melanoma. These drugs have shown clinical benefit over the standard care (dacarbazine); however, they are associated with frequent cutaneous adverse events, which can be concerning to the patient and their physician. Herein, we review the range of cutaneous disorders that seem to be induced by RAF inhibitors, including cutaneous squamous-cell carcinoma, hyperkeratotic lesions, [...]

Mené sur 52 patientes atteintes d'un carcinome séreux ovarien de bas grade, cet essai de phase II évalue, du point de vue de la réponse tumorale objective selon les critères RECIST version 1.1, le selumetininb, un inhibiteur de MEK1/2

Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study

Farley, John ; Brady, William E. ; Vathipadiekal, Vinod ; Lankes, Heather A. ; Coleman, Robert ; Morgan, Mark A. ; Mannel, Robert ; Yamada, S. Diane ; Mutch, David ; Rodgers, William H. ; Birrer, Michael ; Gershenson, David M.

Background : Low-grade serous carcinoma of the ovary is chemoresistant but mutations in the MAPK pathway could be targeted to control tumour growth. We therefore assessed the safety and activity of selumetinib, an inhibitor of MEK1/2, for patients with this cancer. Methods : In this open-label, single-arm phase 2 study, women (aged -18 years) with recurrent low-grade serous ovarian or peritoneal carcinoma were given selumetinib (50 mg twice daily, orally) until progression. The primary endpoint [...]

Cet article passe en revue les travaux récents sur l'utilisation du bevacizumab pour le traitement d'un cancer avancé du sein ou du côlon-rectum chez les patients d'âge supérieur à 65 ans

Bevacizumab in older patients with advanced colorectal or breast cancer

Aprile, Giuseppe ; Ferrari, Laura ; Fontanella, Caterina ; Puglisi, Fabio

The incidence of colorectal and breast cancer is growing among the 550 million living people aged 65 or older. Bevacizumab was the first anti-angiogenic agent approved for the treatment of the advanced phase of these cancers. Although older chronological age still hampers the use of modern treatments, there is a widespread awareness that chronological and physiological (i.e. functional) ages may largely differ, and that seniority itself should not be a stringent limit for the introduction of [...]

Menée sur 35 patients atteints d'un cancer du poumon non à petites cellules de stade II-III et ayant reçu une chimioradiothérapie conventionnelle (âge médian : 63 ans ; durée médiane de suivi : 13 mois), cette étude prospective montre que l'ajout d'une radiothérapie stéréotaxique corporelle peut traiter une tumeur résiduelle sans augmenter le risque de toxicité par rapport à une radiothérapie standard

Stereotactic Body Radiation Therapy Can Be Used Safely to Boost Residual Disease in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study

Feddock, Jonathan ; Arnold, Susanne M. ; Shelton, Brent J. ; Sinha, Partha ; Conrad, Gary ; Chen, Li ; Rinehart, John ; McGarry, Ronald C.

To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. Patients without metastatic disease and with radiologic evidence of limited residual disease (≤5 cm) within the site of the primary tumor and good or complete nodal responses after standard CRT to [...]

Menée sur 30 patients atteints d'un adénocarcinome du pancréas localement avancé et récidivant après une chimiothérapie par gemcitabine, cette étude rétrospective évalue, du point de vue du taux de survie globale, l'efficacité et la toxicité d'une chimioradiothérapie de sauvetage et identifie les facteurs pronostiques associés

Salvage chemoradiotherapy after primary chemotherapy for locally advanced pancreatic cancer: a single-institution retrospective analysis

Mayahara, Hiroshi ; Ito, Yoshinori ; Morizane, Chigusa ; Ueno, Hideki ; Okusaka, Takuji ; Kondo, Shunsuke ; Murakami, Naoya ; Morota, Madoka ; Sumi, Minako ; Itami, Jun

BACKGROUND:There is no consensus on the indication for salvage chemoradiotherapy (CRT) after failure of primary chemotherapy for locally advanced pancreatic cancer (LAPC). Here we report on the retrospective analysis of patients who received salvage CRT after primary chemotherapy for LAPC. The primary objective of this study was to evaluate the efficacy and safety of salvage CRT after primary chemotherapy for LAPC.METHODS:Thirty patients who underwent salvage CRT, after the failure of primary [...]

Mené sur 73 patients atteints d'un cancer rectal de stade cT3-4, cet essai prospectif multicentrique de phase 2 évalue, du point de vue de la régression du stade de la maladie et du grade tumoral, l'efficacité et la toxicité d'une chimioradiothérapie concomitante de courte durée par 5-fluorouracile-leucovorine et suivie d'une intervention chirurgicale

Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

Yeo, Seung-Gu ; Oh, Jae Hwan ; Kim, Dae Yong ; Baek, Ji Yeon ; Kim, Sun Young ; Park, Ji Won ; Kim, Min Ju ; Chang, Hee Jin ; Kim, Tae Hyun ; Lee, Jong Hoon ; Jang, Hong Seok ; Kim, Jun-Gi ; Lee, Myung Ah ; Nam, Taek-Keun

A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus [...]

Mené sur 67 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade III/IVA/IVB et non résécable (âge médian : 56 ans), cet essai randomisé de phase II évalue, du point de vue des taux de survie à 18 mois et du grade associé aux événements indésirables, l'efficacité et la toxicité d'une chimioradiothérapie concomitante combinée au lapatinib

Randomised Phase II study of oral lapatinib combined with chemoradiotherapy in patients with advanced squamous cell carcinoma of the head and neck: Rationale for future randomised trials in human papilloma virus-negative disease

Harrington, Kevin ; Berrier, Alain ; Robinson, Martin ; Remenar, Eva ; Housset, Martin ; de Mendoza, Fernando Hurtado ; Fayette, Jérôme ; Mehanna, Hisham ; El-Hariry, Iman ; Compton, Natalie ; Franklin, Natalie ; Biswas-Baldwin, Nigel ; Lau, Mike ; Legenne, Philippe ; Kumar, Rejnish

Background This randomised Phase II study assessed the activity and safety of concurrent chemoradiotherapy (CRT) and lapatinib followed by maintenance treatment in locally advanced, unresected stage III/IVA/IVB head and neck cancer. Patients and methods Patients were randomised 1:1 to concurrent CRT and placebo followed by placebo or concurrent CRT and lapatinib followed by lapatinib. Treatment continued until disease progression or study withdrawal. Primary end-point was complete response rate [...]

Cet article présente les recommandations CONSORT ("Consolidated Standards of Reporting Trials") en matière d'essais randomisés visant à prouver la non infériorité ou l'équivalence d'une modalité thérapeutique

Reporting of noninferiority and equivalence randomized trials: Extension of the consort 2010 statement

Piaggio G, Elbourne D. R. Pocock S. J. Evans S. W. Altman D. G. Consort Group f

The CONSORT (Consolidated Standards of Reporting Trials) Statement, which includes a checklist and a flow diagram, is a guideline developed to help authors improve the reporting of the findings from randomized controlled trials. It was updated most recently in 2010. Its primary focus is on individually randomized trials with 2 parallel groups that assess the possible superiority of one treatment compared with another. The CONSORT Statement has been extended to other trial designs such as [...]

Cet article présente une approche numérique, objective et systématique, pour identifier les cibles thérapeutiques les plus intéressantes à explorer au sein d'un ensemble de gènes associés au cancer

Objective assessment of cancer genes for drug discovery

Patel, Mishal N. ; Halling-Brown, Mark D. ; Tym, Joseph E. ; Workman, Paul ; Al-Lazikani, Bissan

Selecting the best targets is a key challenge for drug discovery, and achieving this effectively, efficiently and systematically is particularly important for prioritizing candidates from the sizeable lists of potential therapeutic targets that are now emerging from large-scale multi-omics initiatives, such as those in oncology. Here, we describe an objective, systematic, multifaceted computational assessment of biological and chemical space that can be applied to any human gene set to [...]

Cet article analyse les enjeux associés à l'utilisation de critères de jugement de substitution dans le cadre d'essais cliniques d'un traitement ou d'une stratégie préventive des cancers

Surrogate Endpoint Analysis: An Exercise in Extrapolation

Baker, Stuart G. ; Kramer, Barnett S.

Surrogate endpoints offer the hope of smaller or shorter cancer trials. It is, however, important to realize they come at the cost of an unverifiable extrapolation that could lead to misleading conclusions. With cancer prevention, the focus is on hypothesis testing in small surrogate endpoint trials before deciding whether to proceed to a large prevention trial. However, it is not generally appreciated that a small surrogate endpoint trial is highly sensitive to a deviation from the key [...]