Menée sur un modèle murin de sarcome primitif, cette étude montre que les cellules cancéreuses, plutôt que les cellules endothéliales, régulent la réponse tumorale à une radiothérapie stéréotaxique corporelle

Tumor cells, but not endothelial cells, mediate eradication of primary sarcomas by stereotactic body radiation therapy

Moding, Everett J. ; Castle, Katherine D. ; Perez, Bradford A. ; Oh, Patrick ; Min, Hooney D. ; Norris, Hannah ; Ma, Yan ; Cardona, Diana M. ; Lee, Chang-Lung ; Kirsch, David G.

Cancer clinics currently use high-dose stereotactic body radiation therapy as a curative treatment for several kinds of cancers. However, the contribution of vascular endothelial cells to tumor response to radiation remains controversial. Using dual recombinase technology, we generated primary sarcomas in mice with targeted genetic mutations specifically in tumor cells or endothelial cells. We selectively mutated the proapoptotic gene Bax or the DNA damage response gene Atm to genetically [...]

Menée sur 112 patients atteints d'une tumeur carcinoïde bronchique (âge : 16 à 77 ans ; durée minimale de suivi : 5 ans après le début du traitement), cette étude évalue, en fonction du type de tumeur et du point de vue de la mortalité spécifique, l'intérêt d'une résection bronchoscopique en traitement de première ligne

Long-term follow-up after first-line bronchoscopic therapy in patients with bronchial carcinoids

Brokx, Hes A P ; Paul, Marinus A ; Postmus, Pieter E ; Sutedja, Thomas G

Background : Carcinoid of the lung is considered to be a low-grade malignancy. A subgroup presents as an endobronchial tumour. Surgical resection is considered the standard approach because of its metastatic potential and the possibility of an iceberg phenomenon for the endobronchial subgroup. Advances in non-invasive and minimally invasive technologies seem to justify a more lung parenchyma-sparing approach. Methods : In patients presenting with bronchial carcinoids, initial bronchoscopic [...]

Mené à partir de questionnaires auprès de 2 625 atteints d'un cancer de la prostate, cet essai évalue, du point de vue de la préservation de la fonction érectile et de la continence urinaire, l'intérêt d'une prostatectomie radicale laparoscopique assistée par robot par rapport à une prostatectomie radicale par voie ouverte

Urinary Incontinence and Erectile Dysfunction After Robotic Versus Open Radical Prostatectomy: A Prospective, Controlled, Nonrandomised Trial

Haglind, Eva ; Carlsson, Stefan ; Stranne, Johan ; Wallerstedt, Anna ; Wilderäng, Ulrica ; Thorsteinsdottir, Thordis ; Lagerkvist, Mikael ; Damber, Jan-Erik ; Bjartell, Anders ; Hugosson, Jonas ; Wiklund, Peter ; Steineck, Gunnar

Background : Robot-assisted laparoscopic radical prostatectomy (RALP) has become widely used without high-grade evidence of superiority regarding long-term clinical outcomes compared with open retropubic radical prostatectomy (RRP), the gold standard. Objective : To compare patient-reported urinary incontinence and erectile dysfunction 12 mo after RALP or RRP. Design, setting, and participants : This was a prospective, controlled, nonrandomised trial of patients undergoing prostatectomy in 14 [...]

Mené sur 22 patients atteints d'un cancer de la prostate de stade localisé et à risque intermédiaire ou élevé de récidive (durée médiane de suivi : 21 mois), cet essai de phase II évalue l'efficacité, du point de vue de la suppression des androgènes, et la toxicité de l'ajout d'abiratérone à une radiothérapie externe

External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

Cho, Eunpi ; Mostaghel, Elahe A. ; Russell, Kenneth J. ; Liao, Jay J. ; Konodi, Mark A. ; Kurland, Brenda F. ; Marck, Brett T. ; Matsumoto, Alvin M. ; Dalkin, Bruce L. ; Montgomery, R. Bruce

Purpose : Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Methods and [...]

Menée sur 25 patients atteints d'un adénocarcinome rectal extrapéritonéal de stade T1-T2 N0 M0 (durée médiane de suivi : 10 mois), cette étude évalue l'efficacité, du point de vue de la récidive locale, la sécurité et la tolérabilité d'une radiothérapie suivie d'une exérèse transanale par microchirurgie endoscopique

Results of Neoadjuvant Short-Course Radiation Therapy Followed by Transanal Endoscopic Microsurgery for T1-T2 N0 Extraperitoneal Rectal Cancer

Arezzo, Alberto ; Arolfo, Simone ; Allaix, Marco Ettore ; Munoz, Fernando ; Cassoni, Paola ; Monagheddu, Chiara ; Ricardi, Umberto ; Ciccone, Giovannino ; Morino, Mario

Purpose : This study was undertaken to assess the short-term outcomes of neoadjuvant short-course radiation therapy (SCRT) followed by transanal endoscopic microsurgery (TEM) for T1-T2 N0 extraperitoneal rectal cancer. Recent studies suggest that neoadjuvant radiation therapy followed by TEM is safe and has results similar to those with abdominal rectal resection for the treatment of extraperitoneal early rectal cancer. Methods and Materials : We planned a prospective pilot study including 25 [...]

Mené sur 32 patientes atteintes d'un carcinome invasif du sein de stade T1 ou d'un carcinome in situ de grade faible ou intermédiaire (âge : 55 ans ou plus ; durée médiane de suivi : 23 mois), cet essai de phase I évalue la tolérabilité d'une irradiation partielle pré-opératoire du sein par radiothérapie non fractionnée, puis identifie des biomarqueurs associés à la réponse au traitement

Preoperative Single-Fraction Partial Breast Radiotherapy – A Novel Phase I Dose-Escalation Protocol with Radiation Response Biomarkers

Horton, Janet K. ; Blitzblau, Rachel C. ; Yoo, Sua ; Geradts, Joseph ; Chang, Zheng ; Baker, Jay A. ; Georgiade, Gregory S. ; Chen, Wei ; Siamakpour-Reihani, Sharareh ; Wang, Chunhao ; Broadwater, Gloria ; Groth, Jeff ; Palta, Manisha ; Dewhirst, Mark ; Barry, William T. ; Duffy, Eileen A. ; Chi, Jen-Tsan A. ; Hwang, E. Shelley

Purpose : Women with biologically favorable early stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large post-operative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase I trial utilizing widely available technology to 1) evaluate [...]

Menée à partir de données portant sur 108 patients atteints d'un carcinome épidermoïde de l'oropharynx récidivant loco-régionalement ou à distance, cette étude évalue, en fonction du statut HPV de la tumeur, l'intérêt d'un traitement chirurgical de sauvetage pour améliorer la survie globale des patients

Surgical salvage improves overall survival for patients with HPV-positive and HPV-negative recurrent locoregional and distant metastatic oropharyngeal cancer

Guo, Theresa ; Qualliotine, Jesse R. ; Ha, Patrick K. ; Califano, Joseph A. ; Kim, Young ; Saunders, John R. ; Blanco, Ray G. ; D'Souza, Gypsyamber ; Zhang, Zhe ; Chung, Christine H. ; Kiess, Ana ; Gourin, Christine G. ; Koch, Wayne ; Richmon, Jeremy D. ; Agrawal, Nishant ; Eisele, David W. ; Fakhry, Carole

BACKGROUND : Human papillomavirus (HPV) tumor status and surgical salvage are associated with improved prognosis for patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC). Current data regarding types of surgery and the impact of surgery for patients with distant metastatic disease are limited. METHODS : A retrospective analysis of patients with recurrent OPSCC from 2 institutions between 2000 and 2012 was performed. p16 immunohistochemistry and/or in situ hybridization, as [...]

Menée à l'aide de xénogreffes de carcinome hépatocellulaire, cette étude met en évidence l'activité antitumorale d'un composé appelé BLU9931, un inhibiteur de la signalisation FGFR4

First Selective Small Molecule Inhibitor of FGFR4 for the Treatment of Hepatocellular Carcinomas with an Activated FGFR4 Signaling Pathway

Hagel, Margit ; Miduturu, Chandra ; Sheets, Michael ; Rubin, Nooreen ; Weng, Weifan ; Stransky, Nicolas ; Bifulco, Neil ; Kim, Joseph L. ; Hodous, Brian ; Brooijmans, Natasja ; Shutes, Adam ; Winter, Christopher ; Lengauer, Christoph ; Kohl, Nancy E. ; Guzi, Timothy

Aberrant signaling through the fibroblast growth factor 19 (FGF19)/fibroblast growth factor receptor 4 (FGFR 4) signaling complex has been shown to cause hepatocellular carcinoma (HCC) in mice and has been implicated to play a similar role in humans. We have developed BLU9931, a potent and irreversible small-molecule inhibitor of FGFR4, as a targeted therapy to treat patients with HCC whose tumors have an activated FGFR4 signaling pathway. BLU9931 is exquisitely selective for FGFR4 versus other [...]

Cet article passe en revue les travaux récents sur le développement d'inhibiteurs de PARP pour le traitement des patients atteints d'un cancer de l'ovaire ou d'autres tumeurs solides

Poly (ADP-Ribose) Polymerase Inhibitors: Recent Advances and Future Development

Scott, Clare L. ; Swisher, Elizabeth M. ; Kaufmann, Scott H.

Poly (ADP-ribose) polymerase (PARP) inhibitors have shown promising activity in epithelial ovarian cancers, especially relapsed platinum-sensitive high-grade serous disease. Consistent with preclinical studies, ovarian cancers and a number of other solid tumor types occurring in patients with deleterious germline mutations in BRCA1 or BRCA2 seem to be particularly sensitive. However, it is also becoming clear that germline BRCA1/2 mutations are neither necessary nor sufficient for patients to [...]

Menée in vitro et in vivo, cette étude identifie deux anticorps monoclonaux ciblant des glycanes, puis met en évidence leur activité antitumorale dans un modèle de tumeur métastatique colorectale

Monoclonal Antibodies Targeting LecLex-Related Glycans with Potent Anti-Tumor Activity

Jia, Chua X ; Vankemmelbeke, Mireille ; McIntosh, Richard S ; Clarke, Philip A ; Moss, Robert ; Parsons, Tina ; Spendlove, Ian ; Zaitoun, Abid M ; Madhusudan, Srinivasan ; Durrant, Lindy G

Purpose:To produce anti-tumor monoclonal antibodies (mAbs) targetting glycans as they are aberrantly expressed in tumors and are co-accessory molecules for key survival pathways. Experimental Design:Two mAbs (FG88.2 and FG88.7) recognizing novel tumor-associated lewis (Le) glycans were produced by immunizations with plasma membrane lipid extracts of the COLO205 cell line. Results:: Glycan array analysis showed that both mAbs bound LecLex, di-Lea, and LeaLex, as well as Lea-containing glycans. [...]

Cet article passe en revue les perspectives offertes par les travaux récents sur la génomique des leucémies lymphoblastiques aiguës pour le diagnostic de la maladie et la prise en charge des patients

Genomics in acute lymphoblastic leukaemia: insights and treatment implications

Roberts, Kathryn G. ; Mullighan, Charles G.

Acute lymphoblastic leukaemia (ALL) is the commonest childhood cancer and an important cause of morbidity from haematological malignancies in adults. In the past several years, we have witnessed major advances in the understanding of the genetic basis of ALL. Genome-wide profiling studies, including microarray analysis and genome sequencing, have helped identify multiple key cellular pathways that are frequently mutated in ALL such as lymphoid development, tumour suppression, cytokine [...]

Menée ex vivo à partir d'échantillons prélevés sur des patients atteints d'une leucémie myéloïde chronique et inclus dans un essai clinique (18 traités par imatinib, 14 par dasatinib), cette étude met en évidence des mécanismes suggérant l'intérêt de combiner ces inhibiteurs de tyrosine kinase avec une immunothérapie

The Tyrosine Kinase Inhibitors Imatinib and Dasatinib Reduce Myeloid Suppressor Cells and Release Effector Lymphocyte Responses

Christiansson, Lisa ; Soderlund, Stina ; Mangsbo, Sara M ; Hjorth-Hansen, Henrik ; Höglund, Martin ; Markevarn, Berit ; Richter, Johan ; Stenke, Leif ; Mustjoki, Satu ; Loskog, Angelica ; Olsson-Stromberg, Ulla

Immune escape mechanisms promote tumor progression and are hurdles of cancer immunotherapy. Removing immunosuppressive cells before treatment can enhance efficacy. Tyrosine kinase inhibitors may be of interest to combine with immunotherapy since it has been shown that the inhibitor sunitinib reduces myeloid suppressor cells in patients with renal cell carcinoma and dasatinib promotes expansion of natural killer-like lymphocytes in chronic myeloid leukemia. In this study, the capacity of [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes de leucémie lymphoblastique aiguë à précurseurs B BCR-ABL1+ , cette étude met en évidence des mécanismes suggérant l'intérêt d'une stratégie thérapeutique visant à reprogrammer les cellules leucémiques en macrophages

Reprogramming of primary human Philadelphia chromosome-positive B cell acute lymphoblastic leukemia cells into nonleukemic macrophages

McClellan, James Scott ; Dove, Christopher ; Gentles, Andrew J. ; Ryan, Christine E. ; Majeti, Ravindra

BCR–ABL1+ precursor B-cell acute lymphoblastic leukemia (BCR–ABL1+ B-ALL) is an aggressive hematopoietic neoplasm characterized by a block in differentiation due in part to the somatic loss of transcription factors required for B-cell development. We hypothesized that overcoming this differentiation block by forcing cells to reprogram to the myeloid lineage would reduce the leukemogenicity of these cells. We found that primary human BCR–ABL1+ B-ALL cells could be induced to reprogram into [...]

Menée à l'aide de xénogreffes de mélanome, cette étude met en évidence des mécanismes par lesquels un traitement anti-angiogénique est susceptible de favoriser le développement de cellules souches cancéreuses

Induction of vasculogenic mimicry overrides VEGF-A silencing and enriches stem-like cancer cells in melanoma

Schnegg, Caroline I. ; Yang, Moon Hee ; Ghosh, Subrata K. ; Hsu, Mei-Yu

The basis for resistance to VEGF inhibition is not fully understood despite its clinical importance. In this study, we examined the adaptive response to VEGF-A inhibition by a loss-of-function analysis using plasmid-based shRNA. Tumor xenografts that initially responded to VEGF-A inhibition underwent an adaptation in vivo leading to acquired resistance. VEGF-A blockade in tumors was associated with HIF-1α expression and an increase in CD144+ vasculogenic mimicry (VM), leading to formation of [...]

Menée sur des lignées cellulaires, cette étude met en évidence des mécanismes métaboliques suggérant l'intérêt de cibler la protéine LDHA pour surmonter l'apparition d'une résistance au bortézomib dans le traitement d'un myélome multiple

Metabolic signature identifies novel targets for drug resistance in Multiple Myeloma

Maiso, Patricia ; Huynh, Daisy ; Moschetta, Michele ; Sacco, Antonio ; Aljawai, Yosra ; Mishima, Yuji ; Asara, John M. ; Roccaro, Aldo M. ; Kimmelman, Alec C. ; Ghobrial, Irene M.

Drug resistance remains a major clinical challenge for cancer treatment. Multiple myeloma (MM) is an incurable plasma cell cancer selectively localized in the bone marrow (BM). The main cause of resistance in myeloma is the minimal residual disease (MRD) cells that are resistant to the original therapy including bortezomib treatment and high dose melphalan in stem cell transplant. In this study, we demonstrate that altered tumor cell metabolism is essential for the regulation of drug resistance [...]

A partir d'échantillons tumoraux prélevés sur 34 patients atteints d'un cancer du poumon non à petites cellules traité à l'aide de pembrolizumab (un anticorps anti PD-1), cette étude met en évidence un ensemble de mutations associées à la réponse thérapeutique

Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer

Rizvi, Naiyer A. ; Hellmann, Matthew D. ; Snyder, Alexandra ; Kvistborg, Pia ; Makarov, Vladimir ; Havel, Jonathan J. ; Lee, William ; Yuan, Jianda ; Wong, Phillip ; Ho, Teresa S. ; Miller, Martin L. ; Rekhtman, Natasha ; Moreira, Andre L. ; Ibrahim, Fawzia ; Bruggeman, Cameron ; Gasmi, Billel ; Zappasodi, Roberta ; Maeda, Yuka ; Sander, Chris ; Garon, Edward B. ; Merghoub, Taha ; Wolchok, Jedd D. ; Schumacher, Ton N. ; Chan, Timothy A.

Immune checkpoint inhibitors, which unleash a patient’s own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non–small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden in tumors associated with improved objective response, durable clinical benefit, and progression-free [...]

Menée à l'aide de modèles murins, cette étude met en évidence des mécanismes par lesquels le facteur natriurétique auriculaire, utilisé en prophylaxie des complications cardiopulmonaires dans la chirurgie du cancer du poumon, est susceptible d'inhiber le processus métastatique

Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells

Nojiri, Takashi ; Hosoda, Hiroshi ; Tokudome, Takeshi ; Miura, Koichi ; Ishikane, Shin ; Otani, Kentaro ; Kishimoto, Ichiro ; Shintani, Yasushi ; Inoue, Masayoshi ; Kimura, Toru ; Sawabata, Noriyoshi ; Minami, Masato ; Nakagiri, Tomoyuki ; Funaki, Soichiro ; Takeuchi, Yukiyasu ; Maeda, Hajime ; Kidoya, Hiroyasu ; Kiyonari, Hiroshi ; Shioi, Go ; Arai, Yuji ; Hasegawa, Takeshi ; Takakura, Nobuyuki ; Hori, Megumi ; Ohno, Yuko ; Miyazato, Mikiya ; Mochizuki, Naoki ; Okumura, Meinoshin ; Kangawa, Kenji

Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a [...]

Cet article passe en revue les travaux récents sur le développement de thérapies ciblées pour le traitement d'un cancer du poumon à petites cellules

Targeted therapies for small cell lung cancer: where do we stand?

Arcaro, Alexandre

Lung cancer is the leading cause of cancer-related mortality and is subdivided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). SCLC accounts for around 15% of all cases of lung cancer and is associated with cigarette smoking and an extremely dismal prognosis. Standard therapeutic regimens involving chemotherapy and radiotherapy have been improved over the past decades, but without a major impact on long term patient survival. In view of the potentially limited impact [...]

Menée à l'aide de deux xénogreffes dérivées de patients atteints d'un carcinome papillaire à cellules rénales, cette étude évalue l'acitvité antitumorale du savolitinib, un inhibiteur de MET

The MET inhibitor AZD6094 (Savolitinib, HMPL-504) induces regression in papillary renal cell carcinoma patient derived xenograft models

Schuller, Alwin ; Barry, Evan ; Jones, Rhys D.O. ; Henry, Ryan ; Frigault, Melanie M. ; Beran, Garry ; Linsenmayer, David ; Mertens Hattersley, Maureen ; Smith, Aaron ; Wilson, Joanne ; Cairo, Stefano ; Deas, Olivier ; Nicolle, Delphine ; Adam, Ammar ; Zinda, Michael ; Reimer, Corinne ; Fawell, Stephen ; Clark, Edwin ; D'Cruz, Celina

Purpose:Papillary renal cell carcinoma (PRCC) is the second most common cancer of the kidney and carries a poor prognosis for patients with non-localized disease. The HGF receptor MET plays a central role in PRCC and aberrations, either through mutation, copy number gain, or trisomy of chromosome 7 occur in the majority of cases. The development of effective therapies in PRCC has been hampered in part by a lack of available preclinical models. We determined the pharmacodynamic and anti-tumor [...]

Menée à l'aide d'un modèle murin génétiquement modifié, cette étude identifie une population de cellules souches d'un gliome de haut grade qui sont dotées de propriétés leur conférant une résistance thérapeutique

Mouse Low-Grade Gliomas Contain Cancer Stem Cells with Unique Molecular and Functional Properties

Chen, Yi-Hsien ; McGowan, Lucy D’Agostino ; Cimino, Patrick J ; Dahiya, Sonika ; Leonard, Jeffrey R ; Lee, Da Yong ; Gutmann, David H

The availability of adult malignant glioma stem cells (GSCs) has provided unprecedented opportunities to identify the mechanisms underlying treatment resistance. Unfortunately, there is a lack of comparable reagents for the study of pediatric low-grade glioma (LGG). Leveraging a neurofibromatosis 1 (Nf1) genetically engineered mouse LGG model, we report the isolation of CD133+ multi-potent low-grade glioma stem cells (LG-GSCs), which generate glioma-like lesions histologically similar to the [...]

Mené sur 24 et 44 patients atteints d'un myélome multiple récemment diagnostiqué (âge supérieur à 65 ans), cet essai de phase I/II évalue la dose maximale tolérée du carfilzomib, puis l'efficacité, du point de vue du taux de réponse globale, et la toxicité d'un traitement combinant carfilzomib, melphalan et prednisone

Phase I/II study of carfilzomib plus melphalan and prednisone in patients aged over 65 years with newly diagnosed multiple myeloma

Moreau, Philippe ; Kolb, Brigitte ; Attal, Michel ; Caillot, Denis ; Benboubker, Lotfi ; Tiab, Mourad ; Touzeau, Cyrille ; Leleu, Xavier ; Roussel, Murielle ; Chaleteix, Carine ; Planche, Lucie ; Chiffoleau, Anne ; Fortin, June ; Avet-Loiseau, Hervé ; Mary, Jean-Yves ; Hulin, Cyrille ; Facon, Thierry

This phase I/II dose-escalation study investigated the combination of carfilzomib with melphalan and prednisone (CMP) in patients aged >65 years with newly diagnosed multiple myeloma (MM). Melphalan and prednisone were administered orally on days 1–4; carfilzomib was administered intravenously on days 1, 2, 8, 9, 22, 23, 29, and 30 of a 42-day cycle. Patients received up to nine cycles of CMP. In the phase I, dose-escalation portion, the primary objectives were to determine the incidence of [...]

Cet article présente les recommandations d'un groupe d'experts pour le suivi des patients recevant du crizotinib dans le cadre des traitements d'un cancer du poumon non à petites cellules avec réarrangements ALK

Management of crizotinib therapy for ALK-rearranged non-small cell lung carcinoma: An expert consensus

Cappuzzo, Federico ; Moro-Sibilot, Denis ; Gautschi, Oliver ; Boleti, Ekaterini ; Felip, Enriqueta ; Groen, Harry J. M. ; Germonpré, Paul ; Meldgaard, Peter ; Arriola, Edurne ; Steele, Nicola ; Fox, Jesme ; Schnell, Patrick ; Engelsberg, Arne ; Wolf, Jürgen

Within 4 years of the discovery of anaplastic lymphoma kinase (ALK) rearrangements in non-small cell lung cancer (NSCLC), the ALK inhibitor crizotinib gained US and European approval for the treatment of advanced ALK-positive NSCLC. This was due to the striking response data observed with crizotinib in phase I and II trials in patients with ALK-positive NSCLC, as well as the favorable tolerability and safety profile observed. Recently published phase III data established crizotinib as a new [...]

Mené sur 17 patients atteints d'un carcinome à cellules rénales de stade métastatique ou non résécable (âge médian : 62 ans), cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un traitement de première ligne combinant sorafénib et bortézomib

Phase II Study of Sorafenib and Bortezomib for First-Line Treatment of Metastatic or Unresectable Renal Cell Carcinoma

Rao, Arpit ; Lauer, Richard

Background. Sorafenib is an orally active multikinase inhibitor, and bortezomib is a proteasome inhibitor that affects multiple signaling pathways. Sorafenib has clinical activity in renal cell carcinoma (RCC), whereas bortezomib has demonstrated activity against RCC cell lines in vitro, with in vitro studies showing synergism between the two agents in the induction of apoptosis in neoplastic cell lines. In this phase II study, we explored the efficacy and toxicity of this regimen. Methods. [...]

Mené sur 537 patientes atteintes d'un cancer métastatique du sein HER2+, cet essai compare l'efficacité, du point de vue de la survie sans progression, et la toxicité du lapatinib et du trastuzumab dans un traitement de première ligne comprenant un taxane (durée médiane de suivi : 21,5 mois)

Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2–Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31

Gelmon, Karen A. ; Boyle, Frances M. ; Kaufman, Bella ; Huntsman, David G. ; Manikhas, Alexey ; Di Leo, Angelo ; Martin, Miguel ; Schwartzberg, Lee S. ; Lemieux, Julie ; Aparicio, Samuel ; Shepherd, Lois E. ; Dent, Susan ; Ellard, Susan L. ; Tonkin, Katia ; Pritchard, Kathleen I. ; Whelan, Timothy J. ; Nomikos, Dora ; Nusch, Arnd ; Coleman, Robert E. ; Mukai, Hirofumi ; Tjulandin, Sergei ; Khasanov, Rustem ; Rizel, Shulamith ; Connor, Anne P. ; Santillana, Sergio L. ; Chapman, Judith-Anne W. ; Parulekar, Wendy R.

Purpose : The efficacy of lapatinib versus trastuzumab combined with taxanes in the first-line setting of human epidermal growth factor receptor 2 (HER2) –positive metastatic breast cancer (BC) is unknown. Patients and Methods : The MA.31 trial compared a combination of first-line anti-HER2 therapy (lapatinib or trastuzumab) and taxane therapy for 24 weeks, followed by the same anti-HER2 monotherapy until progression. Stratification was by prior (neo)adjuvant anti-HER2 therapy, prior [...]

Mené sur 60 patientes atteintes d'un cancer métastatique du sein triplement négatif, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité de l'ajout du tigazumumab au nab-paclitaxel

TBCRC 019: phase II trial of nab-PAC with/without the anti-death receptor 5 monoclonal antibody tigatuzumab in patients with triple negative breast cancer

Forero-Torres, Andres ; Varley, Katherine E ; Abramson, Vandana ; Li, Yufeng ; Vaklavas, Christos ; Lin, Nancy U ; Liu, Minetta C. ; Rugo, Hope S. ; Nanda, Rita ; Stroniolo, Anna M ; Traina, Tiffany A. ; Patil, Sujata ; Van Poznak, Catherine ; Nangia, Julie R ; Irvin, William J ; Helen, Krontiras ; De Los Santos, Jennifer F ; Haluska, Paul ; Grizzle, William E ; Meyers, Richard M ; Wolff, Antonio C.

Purpose: Tigatuzumab (TIG), an agonistic anti-DR5 antibody, triggers apoptosis in DR5+ human tumor cells without crosslinking. TIG has strong in vitro/in vivo activity against basal-like breast cancer cells enhanced by chemotherapy agents. This study evaluates activity of TIG and chemotherapy in patients with metastatic triple negative breast cancer (TNBC). Experimental Design: Randomized 2:1 phase II trial of albumin-bound paclitaxel (nab-PAC) + TIG in patients with TNBC stratified by prior [...]

Menée à partir d'échantillons sanguins prélevés sur 59 patients atteints d'un cancer rectal et inclus dans un essai de phase II évaluant le bévacizumab en combinaison avec une chimioradiothérapie, cette étude analyse les effets du bévacizumab sur l'expression de marqueurs génétiques et de marqueurs moléculaires, puis évalue l'association entre l'expression de ces marqueurs et la réponse au traitement

Combining bevacizumab and chemoradiation in rectal cancer. Translational results of the AXEBeam trial

Verstraete, M. ; Debucquoy, A. ; Dekervel, J. ; van Pelt, J. ; Verslype, C. ; Devos, E. ; Chiritescu, G. ; Dumon, K. ; D'Hoore, A. ; Gevaert, O. ; Sagaert, X. ; Van Cutsem, E. ; Haustermans, K.

Background : This study characterises molecular effect of bevacizumab, and explores the relation of molecular and genetic markers with response to bevacizumab combined with chemoradiotherapy (CRT). Methods : From a subset of 59 patients of 84 rectal cancer patients included in a phase II study combining bevacizumab with CRT, tumour and blood samples were collected before and during treatment, offering the possibility to evaluate changes induced by one dose of bevacizumab. We performed cDNA [...]