Mené sur 80 patients atteints d'un cancer de la prostate présentant un risque faible ou élevé de métastases ganglionnaires, cet essai de phase II évalue, du point de vue de la survie sans récidive biochimique et des symptômes cliniques, la toxicité et la faisabilité d'une radiothérapie hélicoïdale hypofractionnée avec modulation d'intensité ciblant le lit prostatique avec ou sans les ganglions lymphatiques pelviens

Hypofractionated helical intensity-modulated radiotherapy of the prostate bed after prostatectomy with or without the pelvic lymph nodes - the PRIAMOS trial

Krause, Sonja ; Sterzing, Florian ; Neuhof, Dirk ; Edler, Lutz ; Debus, Juergen ; Herfarth, Klaus

BACKGROUND:While evidence on safety and efficacy of primary hypofractionated radiotherapy in prostate cancer is accumulating, data on postoperative hypofractionated treatment of the prostate bed and of the pelvic lymph nodes is still scarce. This phase II trial was initiated to investigate safety and feasibility of hypofractionated treatment of the prostate bed alone or with the pelvic lymph nodes.METHODS:A total of 80 prostate cancer patients with the indication for adjuvant radiotherapy will [...]

Menée sur 21 patients atteints d'un épendymome intracrânien traité entre 1987 et 2010 (âge : 8 à 70 ans), cette étude évalue, du point de vue de la survie globale à 10 ans et du contrôle tumoral, l'efficacité et la toxicité d'une curiethérapie interstitielle à base de grains d'iode 125 implantés par chirurgie stéréotaxique

Intracranial Ependymoma: Long-Term Results in a Series of 21 Patients Treated with Stereotactic 125Iodine Brachytherapy

El Majdoub, Faycal ; Elawady, Moataz ; Blau, Tobias ; Bührle, Christian ; Hoevels, Mauritius ; Runge, Matthias ; Müller, Rolf-Peter ; Deckert, Martina ; Sturm, Volker ; Maarouf, Mohammad

Background : We evaluated the long-term outcome in patients harboring intracranial ependymomas treated with interstitial brachytherapy (IBT). Methods : Twenty-one patients (M/F = 9/12; median age: 29 years; range: 8–70 years), diagnosed with intracranial ependymoma (1 WHO I, 11 WHO II, 9 WHO III) were treated with IBT using stereotactically implanted 125Iodine seeds between 1987 and 2010, either primarily, as adjuvant therapy following incomplete resection, or as salvage treatment upon tumor [...]

Mené entre 1994 et 2008 sur 110 patients atteints d'un sarcome rétropéritonéal primitif traité par chirurgie agressive de première ligne (âge médian : 52 ans), cette étude française évalue, du point de vue de la récidive locale, de la survie sans récidive et de la survie globale à 5 ans, l'intérêt d'une radiothérapie conformationnelle post-opératoire

Should adjuvant radiotherapy be administered in addition to front-line aggressive surgery (FAS) in patients with primary retroperitoneal sarcoma?

Le Péchoux, C. ; Musat, E. ; Baey, C. ; Al Mokhles, H. ; Terrier, P. ; Domont, J. ; Le Cesne, A. ; Laplanche, A. ; Bonvalot, S.

Background As most patients with retroperitoneal sarcomas (RPS) die of local recurrence, front-line aggressive surgery (FAS) has been developed, and it seems to achieve better local control. The aim of this study was to evaluate conformal postoperative radiotherapy (PORT) in patients who had enlarged surgery.Patients and methods Between 1994 and 2008, 110 patients with primary RPS mainly operated by FAS were analysed. Sixty-two patients underwent surgery and no PORT (group S), and 48 received [...]

Menée sur 111 patients atteints d'un cancer avec métastases cérébrales traitées entre 2001 et 2008 (âge médian : 60 ans ; durée médiane de suivi : 3,8 mois), cette étude rétrospective évalue l'incidence d'une leucoencéphalopathie après une radiothérapie du cerveau entier et identifie les facteurs de risque associés

Incidence of Leukoencephalopathy After Whole-Brain Radiation Therapy for Brain Metastases

Ebi, Junko ; Sato, Hisashi ; Nakajima, Masaru ; Shishido, Fumio

To evaluate the incidence of leukoencephalopathy after whole-brain radiation therapy (WBRT) in patients with brain metastases. We retrospectively reviewed 111 patients who underwent WBRT for brain metastases from April 2001 through March 2008 and had evaluable computed tomography (CT) and/or magnetic resonance imaging (MRI) at least 1 month after completion of WBRT. We evaluated the leukoencephalopathy according to the Common Terminology Criteria for Adverse Events, version 3.0. The patients [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes d'action d'un composé appelé OKN-007, un inhibiteur de l'activité de SULF2, une enzyme jouant un rôle oncogénique dans le carcinome hépatocellulaire

The human sulfatase 2 inhibitor 2,4-disulfonylphenyl-tert-butylnitrone (OKN-007) has an antitumor effect in hepatocellular carcinoma mediated via suppression of TGFB1/SMAD2 and Hedgehog/GLI1 signaling

Zheng, Xin ; Gai, Xiaohong ; Han, Shaoshan ; Moser, Catherine D. ; Hu, Chunling ; Shire, Abdirashid M. ; Floyd, Robert A. ; Roberts, Lewis R.

Human sulfatase 2 (SULF2) functions as an oncoprotein in hepatocellular carcinoma (HCC) development by promoting tumor growth and metastasis via enhancement of fibroblast growth factor-2/extracellular signal-regulated kinase and WNT/β-catenin signaling. Recent results implicate that SULF2 activates the transforming growth factor beta (TGFB) and Hedgehog/GLI1 pathways in HCC. OKN-007 is a novel phenyl–sulfonyl compound that inhibits the enzymatic activity of SULF2. To investigate the antitumor [...]

Menée in vitro et à l'aide de xénogreffes, cette étude évalue l'activité antitumorale d'un composé appelé selenocoxib-1-GSH, un inhibiteur des signalisations COX-2 et PI3K/AKT, pour le traitement des mélanomes

Simultaneous Targeting of COX-2 and AKT Using Selenocoxib-1-GSH to Inhibit Melanoma

Gowda, Raghavendra ; Madhunapantula, SubbaRao V ; Desai, Dhimant ; Amin, Shantu ; Robertson, Gavin P

Melanoma is a highly metastatic and deadly disease. An agent simultaneously targeting COX-2, PI3K/Akt and MAPK signaling pathways that are deregulated in up to 70% of sporadic melanoma might be an effective treatment but no agent of this type exists. To develop a single drug inhibiting COX-2 and PI3K/Akt signaling (and increasing MAPK pathway activity to inhibitory levels as a result of Akt inhibition), a selenium-containing glutathione (GSH) analog of celecoxib, called selenocoxib-1-GSH was [...]

Menée à l'aide d'un modèle murin et sur 14 patientes atteintes d'un cancer ovarien récidivant et résistant aux sels de platine, cette étude met én évidence un nouveau mécanisme immunitaire induit par un protocole de chimiothérapie "dose dense" combinant cisplatine et paclitaxel

Dose-dense chemotherapy improves mechanisms of antitumor immune response

Chang, Chih-Long ; Hsu, Yun-Ting ; Wu, Chao-Chih ; Lai, Yan-Zen ; Wang, Connie ; Yang, Yuh-Cheng ; Wu, T.-C. ; Hung, Chien-Fu

Dose-dense (DD) regimens of combination chemotherapy may produce superior clinical outcomes, but the basis for these effects is not completely clear. In this study, we assessed whether a DD combinatorial regimen of low-dose cisplatin and paclitaxel produces superior immune-mediated efficacy when compared to a maximum-tolerated dose (MTD) regimen, in treating platinum-resistant ovarian cancer as modeled in mice. Immune responses generated by the DD regimen were identified with regard to the [...]

Cet article passe en revue les perspectives offertes par de nouvelles stratégies, notamment des combinaisons de thérapies ciblées, pour le traitement d'un cancer avancé du pancréas

Current concepts and novel targets in advanced pancreatic cancer

Michl, Patrick ; Gress, Thomas M

Pancreatic cancer remains one of the most aggressive tumours with a 5-year survival rate of less than 5%. The dismal prognosis of this tumour entity that is associated with a high degree of drug resistance has not changed over the past decades. Since 1997, gemcitabine-based regimens have been the therapy of choice for advanced pancreatic cancer. Recently, however, new combination chemotherapy regimens achieved a significant survival benefit compared to gemcitabine-based therapies. In addition, [...]

Menée sur des lignées cellulaires d'adénocarcinome pulmonaire, cette étude met en évidence des mécanismes d'action d'un inhibiteur des protéines BET, JQ1

Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins

Lockwood, William W. ; Zejnullahu, Kreshnik ; Bradner, James E. ; Varmus, Harold

Bromodomain and extra terminal domain (BET) proteins function as epigenetic signaling factors that associate with acetylated histones and facilitate transcription of target genes. Inhibitors targeting the activity of BET proteins have shown potent antiproliferative effects in hematological cancers through the suppression of c-MYC and downstream target genes. However, as the epigenetic landscape of a cell varies drastically depending on lineage, transcriptional coactivators such as BETs would be [...]

Mené sur 171 patients atteints d'un adénocarcinome métastatique de l'œsophage distal, de la jonction œsophage-estomac ou de l'estomac, cet essai de phase II évalue, du point de vue de la survie sans progression, l'ajout du trebananib à un traitement combinant cisplatine et capécitabine

Phase II randomized, double-blind, placebo-controlled study of AMG 386 (trebananib) in combination with cisplatin and capecitabine in patients with metastatic gastro-oesophageal cancer

Eatock, M. M. ; Tebbutt, N. C. ; Bampton, C. L. ; Strickland, A. H. ; Valladares-Ayerbes, M. ; Swieboda-Sadlej, A. ; Van Cutsem, E. ; Nanayakkara, N. ; Sun, Y.-N. ; Zhong, Z. D. ; Bass, M. B. ; Adewoye, A. H. ; Bodoky, G.

Background We evaluated AMG 386, an investigational peptibody that neutralizes the interaction between angiopoietins-1 and -2 and the Tie2 receptor, combined with cisplatin/capecitabine (CX) as first-line treatment for metastatic gastro-oesophageal cancer. Patients and Methods Patients with metastatic gastric, gastro-oesophageal junction, or distal oesophageal adenocarcinoma were randomized 1:1:1 to CX (cisplatin 80 mg/m2 IV Q3W; capecitabine 1000 mg/m2 P.O. BID for 14 days Q3W) plus [...]

Cet article passe en revue les travaux récents sur le traitement d'un cancer avancé de l'estomac

Current questions for the treatment of advanced gastric cancer

Cervantes, A. ; Roda, D. ; Tarazona, N. ; Roselló, S. ; Pérez-Fidalgo, J. A.

Gastric cancer remains a major health problem worldwide. Treatment of advanced gastric cancer is controversial and there is no standard regimen for first- or second-line chemotherapy (CT). This review aims to give an overview of the hot topics concerning treatment, prognostic factors and new strategies in advanced gastric cancer. Seven questions of special clinical interest have been formulated previously to the literature review. With the aim of answering each of these questions, a specific [...]

Mené sur 60 patients atteints d'un lymphome T, périphérique ou cutané, récidivant ou réfractaire, cet essai de phase II évalue, du point de vue du taux de réponse globale, la bendumastine en monothérapie

Results From a Prospective, Open-Label, Phase II Trial of Bendamustine in Refractory or Relapsed T-Cell Lymphomas: The BENTLY Trial

Damaj, Gandhi ; Gressin, Rémy ; Bouabdallah, Krimo ; Cartron, Guillaume ; Choufi, Bachra ; Gyan, Emmanuel ; Banos, Anne ; Jaccard, Arnaud ; Park, Sophie ; Tournilhac, Olivier ; Schiano-de Collela, Jean-Marc ; Voillat, Laurent ; Joly, Bertrand ; Le Gouill, Steven ; Saad, Alain ; Cony-Makhoul, Pascale ; Vilque, Jean-Pierre ; Sanhes, Laurence ; Schmidt-Tanguy, Aline ; Bubenheim, Michael ; Houot, Roch ; Diouf, Momar ; Marolleau, Jean-Pierre ; Béné, Marie-Christine ; Martin, Antoine ; Lamy, Thierry

Purpose To determine the efficacy and safety of bendamustine as a single agent in refractory or relapsed T-cell lymphomas. Patients and Methods Patients with histologically confirmed peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma who progressed after one or more lines of prior chemotherapy received bendamustine at 120 mg/m2 per day on days 1 through 2 every 3 weeks for six cycles. The primary end point was overall response rate (ORR). Secondary end points were duration of [...]

Mené sur 48 patients atteints d'un cancer du poumon non à petites cellules avec métastases cérébrales, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'erlotinib en traitement de deuxième ligne

Erlotinib as second-line treatment in patients with advanced non-small-cell lung cancer and asymptomatic brain metastases: a phase II study (CTONG–0803)

Wu, Y.-L. ; Zhou, C. ; Cheng, Y. ; Lu, S. ; Chen, G.-Y. ; Huang, C. ; Huang, Y.-S. ; Yan, H.-H. ; Ren, S. ; Liu, Y. ; Yang, J.-J.

Background This phase II, open-label study evaluated the efficacy and safety of erlotinib as second-line therapy in non-small-cell lung cancer (NSCLC) patients with brain metastases (BM). Patients and methods Forty-eight patients aged 18–75 years with Eastern Cooperative Oncology Group performance status 0–2, confirmed adenocarcinoma or activating epidermal growth factor receptor (EGFR) mutation-positive NSCLC, and asymptomatic BM without extracranial progressive disease after first-line [...]

A partir de données portant sur 1 052 patients atteints d'un cancer avancé du poumon non à petites cellules et inclus dans un essai de phase III, cette étude évalue, chez les patients d'âge supérieur ou égal à 70 ans (15% des participants), la toxicité et l'efficacité du nab-paclitaxel en combinaison avec du carboplatine pour un traitement de première ligne

Safety and efficacy of weekly nab®-paclitaxel in combination with carboplatin as first-line therapy in elderly patients with advanced non-small-cell lung cancer

Socinski, M. A. ; Langer, C. J. ; Okamoto, I. ; Hon, J. K. ; Hirsh, V ; Dakhil, S. R. ; Page, R. D. ; Orsini, J. ; Zhang, H. ; Renschler, M. F.

Background This analysis evaluates safety and efficacy in elderly (≥70 years old) versus younger patients enrolled in a phase III advanced non-small-cell lung cancer (NSCLC) trial. Patients and Methods Untreated stage IIIB/IV patients with PS 0/1 were randomly assigned (1:1) to carboplatin AUC6, day 1 every 3 weeks, and either nab-paclitaxel (Abraxane) 100 mg/m2 weekly (nab-P/C) or solvent-based paclitaxel (Taxol) 200 mg/m2 day 1 every 3 weeks (sb-P/C). The primary end-point was overall [...]

Cet article passe en revue les travaux récents sur le traitement d'un cancer avancé de la prostate

Progress in emerging therapies for advanced prostate cancer

Oudard, Stéphane

The landscape of prostate cancer treatment is rapidly changing as extensive research into potential therapies yields new options. In this article, the literature is reviewed to identify emerging therapies for advanced prostate cancer. Emphasis is placed on agents that have been approved in the United States of America (USA) and the European Union, or that have reached phase III clinical studies. Several new therapies have been approved in recent years across different stages of the natural [...]

Mené sur 80 patients présentant une obstruction intestinale inopérable due à une carcinomatose péritonéale, cet essai de phase III évalue, du point de vue du pourcentage de patients répondant au septième jour, le lanréotide (un analogue de la somatostatine)

Symptomatic Treatment With Lanreotide Microparticles in Inoperable Bowel Obstruction Resulting From Peritoneal Carcinomatosis: A Randomized, Double-Blind, Placebo-Controlled Phase III Study

Mariani, Pascale ; Blumberg, Joëlle ; Landau, Alain ; Lebrun-Jezekova, Daniela ; Botton, Estelle ; Beatrix, Olivier ; Mayeur, Didier ; Herve, Robert ; Maisonobe, Pascal ; Chauvenet, Laure

Purpose To investigate the somatostatin analog lanreotide as symptomatic treatment for inoperable bowel obstruction due to peritoneal carcinomatosis. Patients and Methods In all, 80 patients with peritoneal carcinomatosis, inoperable malignant digestive obstruction, and two or more vomiting episodes per day or nasogastric tube (NGT) who were previously treated with intravenous corticosteroids and proton pump inhibitors were randomly assigned to one 30-mg injection of lanreotide microparticles [...]

Cet article passe en revue les diverses stratégies visant à optimiser l'usage des taxanes pour le traitement d'un cancer du sein métastatique

Optimizing taxane use in MBC in the emerging era of targeted chemotherapy

von Minckwitz, G. ; Martín, M. ; Wilson, G. ; Alba, E. ; Schmidt, M. ; Biganzoli, L. ; Awada, A.

The first-generation taxanes, conventional paclitaxel and docetaxel, are established treatment options for adjuvant and metastatic breast cancer (MBC). However, these agents have limitations, including primary/secondary resistance and harsh toxicities. The introduction of paclitaxel albumin represents a significant advance in taxane therapy as the first of a new generation of taxanes. This agent utilizes albumin pathways to achieve enhanced and targeted drug delivery to the tumour. The lack of [...]

Mené sur 252 patients ayant subi une chirurgie conservatrice pour traiter un sarcome des tissus mous des membres et de la paroi du tronc à haut risque (durée médiane de suivi : 60 mois), cet essai randomisé de phase III évalue, du point de vue de la survie globale à 5 ans et de la récidive locale, l'association entre la qualité des marges de résection et l'efficacité d'une chimiothérapie et d'une radiothérapie néoadjuvantes, seules ou en combinaison

Quality of surgery and neoadjuvant combined therapy in the ISG-GEIS trial on soft tissue sarcomas of limbs and trunk wall

Gronchi, A. ; Verderio, P. ; De Paoli, A. ; Ferraro, A. ; Tendero, O. ; Majò, J. ; Martin, J. ; Comandone, A. ; Grignani, G. ; Pizzamiglio, S. ; Quagliuolo, V. ; Picci, P. ; Frustaci, S. ; Dei Tos, A. P. ; Palassini, E. ; Stacchiotti, S. ; Ferrari, S. ; Fiore, M. ; Casali, P. G.

Background To explore correlation between the quality of surgery and outcome in high-risk soft tissue sarcoma (STS) patients treated within a phase III randomized trial. Patients and Methods In the trial, all patients received three cycles of preoperative chemotherapy (CT) with epirubicin 120 mg/m2 and ifosfamide 9 g/m2 and were randomly assigned to receive two further postoperative cycles. Radiotherapy (RT) could be delivered in the preoperative or postoperative setting. The association [...]

Mené sur 6 patients pédiatriques atteints d'un gliome intrinsèque diffus du pont nouvellement diagnostiqué, cet essai de phase II évalue, du point de vue de la survie globale à 1 an, l'efficacité d'un protocole thérapeutique comportant un traitement par motéxafine et gadolinium (un radiosensibilisant) en combinaison avec une radiothérapie quotidienne fractionnée

Motexafin-Gadolinium and Involved Field Radiation Therapy for Intrinsic Pontine Glioma of Childhood: A Children's Oncology Group Phase 2 Study

Bradley, Kristin A. ; Zhou, Tianni ; McNall-Knapp, Rene Y. ; Jakacki, Regina I. ; Levy, Adam S. ; Vezina, Gilbert ; Pollack, Ian F.

To evaluate the effects on 1-year event-free survival (EFS) and overall survival (OS) of combining motexafin and gadolinium (MGd), a potent radiosensitizer, with daily fractionated radiation therapy in children with newly diagnosed intrinsic pontine gliomas. Patients with newly diagnosed intrinsic pontine glioma were treated with MGd daily for 5 consecutive days each week, for a total of 30 doses. Patients received a 5- to 10-min intravenous bolus of MGd, 4.4 mg/kg/day, given 2 to 5 h prior to [...]

A partir de données portant sur 9 901 patients adultes atteints d'un cancer du poumon ou du côlon-rectum et participant à la cohorte CanCORS du National Cancer Institute, cette étude analyse les déterminants de leur inclusion dans un essai clinique

Enrollment of Patients With Lung and Colorectal Cancers Onto Clinical Trials

Fouad, Mona N. ; Lee, Jeannette Y. ; Catalano, Paul J. ; Vogt, Thomas M. ; Zafar, Syed Yousuf ; West, Dee W. ; Simon, Christian ; Klabunde, Carrie N. ; Kahn, Katherine L. ; Weeks, Jane C. ; Kiefe, Catarina I.

Purpose: Only 2% to 5% of adult patients with cancer enroll onto clinical trials. We assessed simultaneously characteristics of patients and their physicians that may be independently associated with participation. Methods: CanCORS, a National Cancer Institute (NCI) –funded population-based observational cohort study of newly diagnosed patients with lung and colorectal cancers, sampled patients across five geographic areas, five health care delivery systems, and 15 Veterans Administration [...]

Cet article présente les recommandations d'un groupe d'experts en oncologie pédiatrique pour livrer les résultats d'un projet de recherche aux participants

Recommendations for the Return of Research Results to Study Participants and Guardians: A Report From the Children’s Oncology Group

Fernandez, Conrad V. ; Ruccione, Kathleen ; Wells, Robert J. ; Long, Jay B. ; Pelletier, Wendy ; Hooke, Mary C. ; Pentz, Rebecca D. ; Noll, Robert B. ; Baker, Justin N. ; O’Leary, Maura ; Reaman, Gregory ; Adamson, Peter C. ; Joffe, Steven

Purpose The Children’s Oncology Group (COG) strongly supports the widely recognized principle that research participants should be offered a summary of study results. The mechanism by which to do so in a cooperative research group setting has not been previously described.Methods On the basis of a review of the available empirical and theoretic literature and on iterative, multidisciplinary discussion, a COG Return of Results Task Force (RRTF) offered detailed recommendations for the return of [...]