Menée sur 225 patients atteints d'un cancer colorectal, cette étude compare, par rapport à une hépatectomie partielle et du point de vue de la survie, des niveaux de marqueurs angiogéniques ou de l'évolution du profil protéique dans le sérum, l'efficacité de deux techniques de résection pour traiter des métastases hépatiques : l'une utilisant la cryochirurgie et l'autre les radiofréquences

Clinical outcome, proteome kinetics and angiogenic factors in serum after thermoablation of colorectal liver metastases

Wertenbroek, Marieke ; Schepers, Marianne ; Kamminga-Rasker, Hannetta ; Bottema, Jan ; Muller Kobold, Anneke ; Roelofsen, Han ; de Jong, Koert

BACKGROUND : Thermoablation is used to treat patients with unresectable colorectal liver metastases (CRLM). We analyze clinical outcome, proteome kinetics and angiogenic markers in patients treated by cryosurgical ablation (CSA) or radiofrequency ablation (RFA). METHODS : 205 patients underwent CSA (n = 20), RFA (n = 22), partial hepatectomy (PH, n = 134) or were found truly unresectable (n = 29). Clinical outcome, proteome transitions and angiogenic response in serum were analyzed at various [...]

Menée à partir de données médicales portant sur 20 patients atteints d'un lymphome non hodgkinien des annexes oculaires (durée médiane de suivi : 26 mois), cette étude évalue l'efficacité, du point de vue de la récidive locale à 2 ans, et la toxicité d'un protocole de radiothérapie comportant deux faibles doses de rayonnements ionisants (2 Gy)

Low-Dose Radiation Therapy (2 Gy × 2) in the Treatment of Orbital Lymphoma

Fasola, Carolina E. ; Jones, Jennifer C. ; Huang, Derek D. ; Le, Quynh-Thu ; Hoppe, Richard T. ; Donaldson, Sarah S.

Purpose : Low-dose radiation has become increasingly used in the management of indolent non-Hodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa. Methods and Materials : We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive [...]

Cet article passe en revue les nouvelles techniques d'imagerie permettant d'améliorer la précision de l'irradiation des ganglions lymphatiques chez les patients atteints d'un cancer de la prostate

Individualized image-based lymph node irradiation for prostate cancer

Meijer, Hanneke J. M. ; Debats, Oscar A. ; Th. van Lin, Emile N. J. ; van Vulpen, Marco ; Witjes, J. Alfred ; Oyen, Wim J. G. ; Barentsz, Jelle O. ; Kaanders, Johannes H. A. M.

Controversy surrounds the benefit of whole pelvis radiotherapy (WPRT) over prostate-only radiotherapy (PORT) for intermediate-risk and high-risk patients with prostate cancer. In the PSA screening era, two large randomized trials as well as multiple retrospective studies comparing WPRT with PORT have been performed, albeit with contradictory results. Data regarding the use of WPRT in patients with biochemical recurrence after prostatectomy are scarce. As a consequence, the practice of WPRT [...]

Menée à partir de données médicales portant sur 462 patients adultes atteints d'un sarcome des tissus mous du tronc ou des extrémités et traités par résection chirurgicale puis radiothérapie adjuvante entre 1998 et 2009, cette étude multicentrique évalue l'effet de différentes doses fractionnées de rayonnements ionisants sur le taux de récidive locale et identifie les facteurs de risque associés

Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall

Jebsen, Nina L. ; Engellau, Jacob ; Engström, Katarina ; Bauer, Henrik C. ; Monge, Odd R. ; Muren, Ludvig P. ; Eide, Geir E. ; Trovik, Clement S. ; Bruland, Øyvind S.

Purpose : To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials : LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. [...]

Mené sur 52 patientes atteintes d'un cancer du sein de stade I ou II traité par tumorectomie (nombre de ganglions positifs : ≤ 3 ; marges de résection négatives ; durée médiane de suivi : 5,3 ans), cet essai de phase II évalue la toxicité à long terme d'une irradiation partielle accélérée du sein par radiothérapie conformationnelle 3D, puis analyse le niveau de satisfaction des patientes vis-à-vis du traitement et des résultats esthétiques obtenus

Late Toxicity and Patient Self-Assessment of Breast Appearance/Satisfaction on RTOG 0319 : A Phase 2 Trial of 3-Dimensional Conformal Radiation Therapy-Accelerated Partial Breast Irradiation Following Lumpectomy for Stages I and II Breast Cancer

Chafe, Susan ; Moughan, Jennifer ; McCormick, Beryl ; Wong, John ; Pass, Helen ; Rabinovitch, Rachel ; Arthur, Douglas W. ; Petersen, Ivy ; White, Julia ; Vicini, Frank A.

Purpose : Late toxicities and cosmetic analyses of patients treated with accelerated partial breast irradiation (APBI) on RTOG 0319 are presented. Methods and Materials : Patients with stages I to II breast cancer ≤3 cm, negative margins, and ≤3 positive nodes were eligible. Patients received three-dimensional conformal external beam radiation therapy (3D-CRT; 38.5 Gy in 10 fractions twice daily over 5 days). Toxicity and cosmesis were assessed by the patient (P), the radiation oncologist (RO), [...]

Cet article fait le point sur les avantages de la tomothérapie hélicoïdale dans le traitement des cancers de la tête et du cou

The Potential of Helical Tomotherapy in the Treatment of Head and Neck Cancer

Van Gestel, Dirk ; Verellen, Dirk ; Van De Voorde, Lien ; de Ost, Bie ; De Kerf, Geert ; Vanderveken, Olivier ; Van Laer, Carl ; Van den Weyngaert, Danielle ; Vermorken, Jan B. ; Gregoire, Vincent

A decade after its first introduction into the clinic, little is known about the clinical impact of helical tomotherapy (HT) on head and neck cancer (HNC) treatment. Therefore, we analyzed the basics of this technique and reviewed the literature regarding HT's potential benefit in HNC. The past two decades have been characterized by a huge technological evolution in photon beam radiotherapy (RT). In HNC, static beam intensity-modulated radiotherapy (IMRT) has shown superiority over [...]

Menée in vitro et in vivo sur des modèles de cancer du poumon et du pancréas, cette étude met en évidence des mécanismes par lesquels, en induisant une hypoxie, le nintedanib exerce une activité antitumorale et antiangiogénique

BIBF 1120 (Nintedanib), a Triple Angiokinase Inhibitor, Induces Hypoxia but not EMT and Blocks Progression of Preclinical Models of Lung and Pancreatic Cancer

Kutluk Cenik, Bercin ; Ostapoff, Katherine T. ; Gerber, David E. ; Brekken, Rolf A.

Signaling from other angiokinases may underlie resistance to VEGF-directed therapy. We evaluated the antitumor and biologic effects of BIBF 1120 (nintedanib), a tyrosine kinase inhibitor that targets VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor in preclinical models of lung and pancreatic cancer, including models resistant to VEGF-targeted treatments. In vitro, BIBF 1120 did not show antiproliferative effects, nor did it sensitize tumor cells to [...]

Menée in vitro et in vivo, cette étude évalue l'intérêt d'utiliser un variant du récepteur SIRPα pour augmenter l'efficacité de traitements anticancéreux à base d'anticorps

Engineered SIRPα Variants as Immunotherapeutic Adjuvants to Anticancer Antibodies

Weiskopf, Kipp ; Ring, Aaron M. ; Ho, Chia Chi M. ; Volkmer, Jens-Peter ; Levin, Aron M. ; Volkmer, Anne Kathrin ; Özkan, Engin ; Fernhoff, Nathaniel B. ; van de Rijn, Matt ; Weissman, Irving L. ; Garcia, K. Christopher

CD47 is an antiphagocytic signal that cancer cells employ to inhibit macrophage-mediated destruction. Here, we modified the binding domain of human SIRPα, the receptor for CD47, for use as a CD47 antagonist. We engineered high-affinity SIRPα variants with approximately 50,000-fold increased affinity for human CD47 relative to wild-type SIRPα. As high-affinity SIRPα monomers, they potently antagonized CD47 on cancer cells but did not induce macrophage phagocytosis on their own. Instead, they [...]

Menée in vitro et à l'aide de xénogreffes, cette étude évalue l'activité anti-leucémique de nanoparticules enrichies en rituximab et en Nutline-3

Nanoparticles engineered with Rituximab and loaded with Nutlin-3 show promising therapeutic activity in B leukemic xenografts

Voltan, Rebecca ; Secchiero, Paola ; Ruozi, Barbara ; Forni, Flavio ; Agostinis, Chiara ; Caruso, Lorenzo ; Vandelli, Maria Angela ; Zauli, Giorgio

Purpose: Since the non-genotoxic inhibitor of the p53/MDM2 interactions Nutlin-3 has shown promising in vitro therapeutic activity against a variety of p53wild-type cancer cells, in this study we evaluated an innovative strategy able to specifically target Nutlin-3 towards CD20+ malignant cells. Experimental Design: The cytotoxic effects of Nutlin-3 encapsulated into poly(lactide-co-glycolide) nanoparticles (NP-Nut) and into Rituximab (anti-CD20 Antibody)-engineered NP (NP-Rt-Nut) as well as of [...]

Menée in vitro et à l'aide de xénogreffes, cette étude suggère l'intérêt de petites molécules activant la kinase PKM2 pour le traitement d'un adénocarcinome du poumon

Pharmacological activation of PKM2 slows lung tumor xenograft growth

Parnell, K. Mark ; Foulks, Jason M ; Nix, Rebecca N ; Clifford, Adrianne ; Bullough, Jeremy ; Luo, Bai ; Senina, Anna ; Vollmer, David ; Liu, Jihua ; McCarthy, Virgil ; Xu, Yong ; Saunders, Michael ; Liu, Xiao-Hui ; Pearce, Scott ; Wright, Kevin ; O'Reily, Marc ; McCullar, Michael V ; Ho, Koc-Kan ; Kanner, Steven B.

Inactivation of the M2 form of pyruvate kinase (PKM2) in cancer cells is associated with increased tumorigenicity. To test the hypothesis that tumor growth may be inhibited through the PKM2 pathway, we generated a series of small molecule PKM2 activators. The compounds exhibited low nM activity in both biochemical and cell-based PKM2 activity assays. These compounds did not affect the growth of cancer cell lines under normal conditions in vitro, but strongly inhibited the proliferation of [...]

Menée à l'aide de xénogreffes, cette étude identifie des populations cellulaires impliquées dans la récidive d’un cancer de la prostate résistant à la castration

A Preclinical Xenograft Model Identifies Castration-Tolerant Cancer-Repopulating Cells in Localized Prostate Tumors

Toivanen, Roxanne ; Frydenberg, Mark ; Murphy, Declan ; Pedersen, John ; Ryan, Andrew ; Pook, David ; Berman, David M. ; Australian Prostate Cancer BioResource ; Taylor, Renea A. ; Risbridger, Gail P.

A lack of clinically relevant experimental models of human prostate cancer hampers evaluation of potential therapeutic agents. Currently, androgen deprivation therapy is the gold standard treatment for advanced prostate cancer, but inevitably, a subpopulation of cancer cells survives and repopulates the tumor. Tumor cells that survive androgen withdrawal are critical therapeutic targets for more effective treatments, but current model systems cannot determine when they arise in disease [...]

A partir de données fournies par le traitement de modèles murins et de données cliniques portant sur des patients, cette étude met en évidence l'intérêt d'une analyse intégrée pour le développement de traitements d'un cancer de la prostate résistant à la castration

A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer

Lunardi, Andrea ; Ala, Ugo ; Epping, Mirjam T. ; Salmena, Leonardo ; Clohessy, John G. ; Webster, Kaitlyn A. ; Wang, Guocan ; Mazzucchelli, Roberta ; Bianconi, Maristella ; Stack, Edward C. ; Lis, Rosina ; Patnaik, Akash ; Cantley, Lewis C. ; Bubley, Glenn ; Cordon-Cardo, Carlos ; Gerald, William L. ; Montironi, Rodolfo ; Signoretti, Sabina ; Loda, Massimo ; Nardella, Caterina ; Pandolfi, Pier Paolo

Here we report an integrated analysis that leverages data from treatment of genetic mouse models of prostate cancer along with clinical data from patients to elucidate new mechanisms of castration resistance. We show that castration counteracts tumor progression in a Pten loss–driven mouse model of prostate cancer through the induction of apoptosis and proliferation block. Conversely, this response is bypassed with deletion of either Trp53 or Zbtb7a together with Pten, leading to the [...]

Menée in vitro et in vivo, cette étude met en évidence le rôle joué par une amplification du récepteur MET dans la résistance à un traitement anti-EGFR de tumeurs colorectales sans mutations KRAS

Amplification of the MET Receptor Drives Resistance to Anti-EGFR Therapies in Colorectal Cancer

Bardelli, Alberto ; Corso, Simona ; Bertotti, Andrea ; Hobor, Sebastijan ; Valtorta, Emanuele ; Siravegna, Giulia ; Sartore-Bianchi, Andrea ; Scala, Elisa ; Cassingena, Andrea ; Zecchin, Davide ; Apicella, Maria ; Migliardi, Giorgia ; Galimi, Francesco ; Lauricella, Calogero ; Zanon, Carlo ; Perera, Timothy ; Veronese, Silvio ; Corti, Giorgio ; Amatu, Alessio ; Gambacorta, Marcello ; Diaz, Luis A. ; Sausen, Mark ; Velculescu, Victor E. ; Comoglio, Paolo ; Trusolino, Livio ; Di Nicolantonio, Federica ; Giordano, Silvia ; Siena, Salvatore

EGF receptor (EGFR)-targeted monoclonal antibodies are effective in a subset of metastatic colorectal cancers. Inevitably, all patients develop resistance, which occurs through emergence of KRAS mutations in approximately 50% of the cases. We show that amplification of the MET proto-oncogene is associated with acquired resistance in tumors that do not develop KRAS mutations during anti-EGFR therapy. Amplification of the MET locus was present in circulating tumor DNA before relapse was [...]

Menée in vitro et in vivo, cette étude met en évidence le rôle joué par la surexpression du récepteur TLR4 dans la réponse au paclitaxel d'un cancer du sein

TLR4 is a novel determinant of the response to paclitaxel in breast cancer

Rajput, Sandeep ; Volk-Draper, Lisa D. ; Ran, Sophia

Overexpression of Toll-like Receptor-4 (TLR4) in human tumors often correlates with chemoresistance and metastasis. We found that TLR4 is overexpressed in the majority of clinical breast cancer (BC) samples and in 68% of the examined BC lines. TLR4 is activated by lipopolysaccharide (LPS) and other ligands including the widely-used drug paclitaxel (PXL). LPS is frequently used to show a tumor-promoting role of TLR4 although this bacterial component is unlikely to be found in BC environment. We [...]

Mené sur 58 patients pédiatriques atteints d'une leucémie récidivante ou réfractaire à l'imatinib, cet essai de phase I évalue l'efficacité et la toxicité du dasatinib

Dasatinib in Children and Adolescents With Relapsed or Refractory Leukemia: Results of the CA180-018 Phase I Dose-Escalation Study of the Innovative Therapies for Children With Cancer Consortium

Zwaan, C. Michel ; Rizzari, Carmelo ; Mechinaud, Francoise ; Lancaster, Donna L. ; Lehrnbecher, Thomas ; van der Velden, Vincent H.J. ; Beverloo, B. Berna ; den Boer, Monique L. ; Pieters, Rob ; Reinhardt, Dirk ; Dworzak, Michael ; Rosenberg, Julie ; Manos, George ; Agrawal, Shruti ; Strauss, Lewis ; Baruchel, André ; Kearns, Pamela R.

Purpose Dasatinib is a potent BCR-ABL inhibitor with proven efficacy in adults with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP) and in imatinib-resistant/intolerant disease. This phase I study of the Innovative Therapies for Children with Cancer Consortium assessed dasatinib safety and efficacy in pediatric patients. Patients and Methods Escalating once-daily dasatinib doses (60 to 120 mg/m2) were administered to children (n = 58) with (i) imatinib-pretreated CML or [...]

Mené sur 91 patients atteints d'un mélanome métastatique présentant une mutation du gène BRAF, cet essai de phase II évalue, du point de vue de la survie globale, l'ajout de selumetinib, un inhibiteur de MEK1/2, à un traitement de première ligne à l'aide de dacarbazine

Selumetinib plus dacarbazine versus placebo plus dacarbazine as first-line treatment for BRAF-mutant metastatic melanoma: a phase 2 double-blind randomised study

Robert, Caroline ; Dummer, Reinhard ; Gutzmer, Ralf ; Lorigan, Paul ; Kim, Kevin B. ; Nyakas, Marta ; Arance, Ana ; Liszkay, Gabriella ; Schadendorf, Dirk ; Cantarini, Mireille ; Spencer, Stuart ; Middleton, Mark R.

Background : Patients with metastatic melanoma, 50% of whose tumours harbour a BRAF mutation, have a poor prognosis. Selumetinib, a MEK1/2 inhibitor, has shown antitumour activity in patients with BRAF-mutant melanoma and in preclinical models when combined with chemotherapy. This study was designed to look for a signal of improved efficacy by comparing the combination of selumetinib and dacarbazine with dacarbazine alone. Methods : This double-blind, randomised, placebo-controlled phase 2 [...]

Cet article passe en revue les perspectives cliniques offertes par les différents agents d'immunothérapie ayant reçu une autorisation de mise sur le marché pour le traitement d'un mélanome métastatique

Immunotherapy for advanced melanoma: Fulfilling the promise

Gogas, Helen ; Polyzos, Aristidis ; Kirkwood, John

The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9months. Over the past thirty years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination [...]

Mené sur 347 patients atteints d'un cancer du poumon avec réarrangement du gène ALK de stade localement avancé ou métastatique, cet essai de phase III compare, du point de vue de la survie sans progression, le crizotinib avec une chimiothérapie à base de pemetrexed ou docétaxel

Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer

Shaw, Alice T. ; Kim, Dong-Wan ; Nakagawa, Kazuhiko ; Seto, Takashi ; Crino, Lucio ; Ahn, Myung-Ju ; De Pas, Tommaso ; Besse, Benjamin ; Solomon, Benjamin J. ; Blackhall, Fiona ; Wu, Yi-Long ; Thomas, Michael ; O'Byrne, Kenneth J. ; Moro-Sibilot, Denis ; Camidge, D. Ross ; Mok, Tony ; Hirsh, Vera ; Riely, Gregory J. ; Iyer, Shrividya ; Tassell, Vanessa ; Polli, Anna ; Wilner, Keith D. ; Jänne, Pasi A.

Background : In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown. Methods : We conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had [...]

Menée sur un patient atteint d'un adénocarcinome métastatique du poumon présentant un réarrangement CD74-ROS1, cette étude identifie, dans la tumeur et toutes les métastases, une mutation somatique dans le codon 2032 du domaine kinase du gène ROS1 rendant compte de la résistance au crizotinib

Acquired Resistance to Crizotinib from a Mutation in CD74–ROS1

Awad, Mark M. ; Katayama, Ryohei ; McTigue, Michele ; Liu, Wei ; Deng, Ya-Li ; Brooun, Alexei ; Friboulet, Luc ; Huang, Donghui ; Falk, Matthew D. ; Timofeevski, Sergei ; Wilner, Keith D. ; Lockerman, Elizabeth L. ; Khan, Tahsin M. ; Mahmood, Sidra ; Gainor, Justin F. ; Digumarthy, Subba R. ; Stone, James R. ; Mino-Kenudson, Mari ; Christensen, James G. ; Iafrate, A. John ; Engelman, Jeffrey A. ; Shaw, Alice T.

Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), has also recently shown efficacy in the treatment of lung cancers with ROS1 translocations. Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74–ROS1 rearrangement who had initially shown a dramatic response to treatment. We performed a biopsy of a resistant tumor and identified an acquired mutation leading to a glycine-to-arginine substitution at codon 2032 in the ROS1 kinase domain. [...]

Mené sur 711 patients atteints d'un sarcome avancé, cet essai international de phase III évalue, du point de vue de la survie sans progression, le ridaforolimus, un inhibiteur de mTOR, en traitement d'entretien

Results of an International Randomized Phase III Trial of the Mammalian Target of Rapamycin Inhibitor Ridaforolimus Versus Placebo to Control Metastatic Sarcomas in Patients After Benefit From Prior Chemotherapy

Demetri, George D. ; Chawla, Sant P. ; Ray-Coquard, Isabelle ; Le Cesne, Axel ; Staddon, Arthur P. ; Milhem, Mohammed M. ; Penel, Nicolas ; Riedel, Richard F. ; Bui-Nguyen, Binh ; Cranmer, Lee D. ; Reichardt, Peter ; Bompas, Emmanuelle ; Alcindor, Thierry ; Rushing, Daniel ; Song, Yang ; Lee, Ruey-min ; Ebbinghaus, Scot ; Eid, Joseph E. ; Loewy, John W. ; Haluska, Frank G. ; Dodion, Pierre F. ; Blay, Jean-Yves

Purpose Aberrant mammalian target of rapamycin (mTOR) signaling is common in sarcomas and other malignancies. Drug resistance and toxicities often limit benefits of systemic chemotherapy used to treat metastatic sarcomas. This large randomized placebo-controlled phase III trial evaluated the mTOR inhibitor ridaforolimus to assess maintenance of disease control in advanced sarcomas. Patients and Methods Patients with metastatic soft tissue or bone sarcomas who achieved objective response or [...]

Menée sur des cellules de gliome ou de carcinome de la parotide radiorésistantes et à l'aide de xénogreffes, cette étude montre que l'inhibition de la protéine kinase mTOR peut rétablir la sensibilité des cellules cancéreuses aux rayonnements ionisants et favoriser leur sénescence

Radioresistant Cancer Cells Can Be Conditioned to Enter Senescence by mTOR Inhibition

Nam, Hae Yun ; Han, Myung Woul ; Chang, Hyo Won ; Lee, Yoon Sun ; Lee, Myungjin ; Lee, Hyang Ju ; Lee, Byoung Wook ; Lee, Hee Jin ; Lee, Kyung Eun ; Jung, Min Kyo ; Jeon, Hyesung ; Choi, Seung-Ho ; Park, Neung Hwa ; Kim, Sang Yoon ; Kim, Seong Who

Autophagy is frequently activated in radioresistant cancer cells where it provides a cell survival strategy. The mTOR inhibitor rapamycin activates autophagy but paradoxically it also enhances radiosensitivity. In this study, we investigated the mechanisms of these opposing actions in radiation-resistant glioma or parotid carcinoma cells. Radiation treatment transiently enhanced autophagic flux for a period of 72 hours in these cells and treatment with rapamycin or the mTOR inhibitor PP242 [...]

Menée sur 89 patients atteints d'un cancer du poumon non à petites cellules de stade IIIB et âgés d'au moins 70 ans, cette étude rétrospective évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité d'une chimioradiothérapie concomitante agressive à base de cisplatine

Outcomes of aggressive concurrent radiochemotherapy in highly selected septuagenarians with stage IIIB non-small cell lung carcinoma: Retrospective analysis of 89 patients

Topkan, Erkan ; Parlak, Cem ; Topuk, Savas ; Guler, Ozan Cem ; Selek, Ugur

We retrospectively evaluated the toxicity and efficacy of concurrent radiochemotherapy (C-RCT) in medically fit septuagenarians with stage IIIB non-small cell lung carcinoma (NSCLC). Eighty-nine medically fit, stage IIIB NSCLC septuagenarians were included. Thoracic radiotherapy to a total dose of 66 Gy in 2 Gy fractions was delivered concurrently with 1–2 cycles of cisplatin-based doublet chemotherapy. Treatment was relatively well-tolerated with no grade 4/5 acute toxicity. Acute grade 3 [...]

Mené sur 25 patients atteints d'un glioblastome récemment diagnostiqué, cet essai de phase I évalue la toxicité de l'évérolimus, un inhibiteur de mTOR, administré quotidiennement par voie orale et combiné de manière concomitante à une radiothérapie et au témozolomide

RTOG 0913: A Phase 1 Study of Daily Everolimus (RAD001) in Combination With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

Chinnaiyan, Prakash ; Won, Minhee ; Wen, Patrick Y. ; Rojiani, Amyn M. ; Wendland, Merideth ; DiPetrillo, Thomas A. ; Corn, Benjamin W. ; Mehta, Minesh P.

Purpose : To determine the safety of the mammalian target of rapamycin inhibitor everolimus (RAD001) administered daily with concurrent radiation and temozolomide in newly diagnosed glioblastoma patients. Methods and Materials : Everolimus was administered daily with concurrent radiation (60 Gy in 30 fractions) and temozolomide (75 mg/m2 per day). Everolimus was escalated from 2.5 mg/d (dose level 1) to 5 mg/d (dose level 2) to 10 mg/d (dose level 3). Adjuvant temozolomide was delivered at 150 [...]

Mené sur 15 patients atteints d'un gliome malin récidivant et ayant subi en traitement initial une intervention chirurgicale, une radiothérapie adjuvante combinée au témozolomide puis une chimiothérapie de sauvetage, cet essai prospectif évalue les effets toxiques, sur le système nerveux central, d'une radiochirurgie stéréotaxique combinée de manière concomitante au bévacizumab

Concurrent Stereotactic Radiosurgery and Bevacizumab in Recurrent Malignant Gliomas: A Prospective Trial

Cabrera, Alvin R. ; Cuneo, Kyle C. ; Desjardins, Annick ; Sampson, John H. ; McSherry, Frances ; Herndon, James E. ; Peters, Katherine B. ; Allen, Karen ; Hoang, Jenny K. ; Chang, Zheng ; Craciunescu, Oana ; Vredenburgh, James J. ; Friedman, Henry S. ; Kirkpatrick, John P.

Purpose : Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. Methods and Materials : Fifteen patients with recurrent MG, treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen, were enrolled in this prospective trial. Lesions <3 cm in diameter [...]

Cet article propose des critères détaillés précisant l'appellation "Breakthrough Therapy" mise en place par l'autorité réglementaire américaine pour accélérer le processus d'autorisation de mise sur le marché de nouveaux médicaments ou traitements ayant démontré une réponse spectaculaire dans des essais de phase précoce

Developing Standards for Breakthrough Therapy Designation in Oncology

Horning, Sandra J ; Haber, Daniel A ; Selig, Wendy KD ; Ivy, Percy ; Roberts, Samantha A ; Allen, Jeffrey ; Sigal, Ellen V ; Sawyers, Charles L

In July 2012, Congress passed the Food and Drug Administration Safety and Innovation Act (FDASIA). The Advancing Breakthrough Therapies for Patients Act was incorporated into a Title of FDASIA to expedite clinical development of new, potential "breakthrough" drugs or treatments that show dramatic responses in early phase studies. Using this regulatory pathway, once a promising new drug candidate is designated as a "Breakthrough Therapy", the FDA and sponsor would collaborate to determine the [...]

Cet article analyse les caractéristiques d'une modalité récemment mise en place par l'agence réglementaire américaine pour accélérer le processus d'autorisation de mise sur le marché de nouveaux médicaments, principalement dans le traitement des cancers

Cancer's true breakthroughs

Dolgin, Elie

A new regulatory pathway established last year allows drugs with dramatic early clinical promise to be expedited to the market quicker than ever before. To date, most of these 'breakthrough' designations have gone to cancer agents, raising the prospect of faster access to the latest lifesaving therapies for the estimated 4,500 people newly diagnosed with cancer each day in the US. Elie Dolgin looks at what sets these breakthrough medicines apart.