Cet article passe en revue les études récentes concernant l'utilisation de certains radionucléides à émission de particules alpha pour traiter des micrométastases ou des cancers localisés sans endommager les tissus environnants

Molecular Pathways: Targeted α-Particle Radiation Therapy

Baidoo, Kwamena E ; Yong, Kwon ; Brechbiel, Martin W

An α-particle, a 4He nucleus, is exquisitely cytotoxic, and indifferent to many limitations associated with conventional chemo- and radiotherapy. The exquisite cytotoxicity of α radiation, the result of its high mean energy deposition (high linear energy transfer, LET) and limited range in tissue, provides for a highly controlled therapeutic modality that can be targeted to selected malignant cells (targeted α-therapy (TAT)) with minimal normal tissue effects. There is a burgeoning interest in [...]

Menée sur 41 patients atteints d'un lymphome médiastinal primitif à grandes cellules B et ayant reçu une chimiothérapie par doxorubicine, cette étude évalue, du point de vue du contrôle local de la maladie et de la survie globale à 5 ans, l'efficacité et la toxicité d'une radiothérapie avec modulation d'intensité en fonction de la dose de rayonnements administrée

Dosimetric Evaluation and Treatment Outcome of Intensity Modulated Radiation Therapy After Doxorubicin-Based Chemotherapy for Primary Mediastinal Large B-Cell Lymphoma

Xu, Li-Ming ; Li, Ye-Xiong ; Fang, Hui ; Jin, Jing ; Wang, Wei-Hu ; Wang, Shu-Lian ; Liu, Yue-Ping ; Song, Yong-Wen ; Liu, Qing-Feng ; Chen, Bo ; Qi, Shu-Nan ; Ren, Hua ; Dai, Jian-Rong

The value of intensity-modulated radiation therapy (IMRT) after doxorubicin-based chemotherapy in primary mediastinal large B-cell lymphoma (PMBCL) is unknown. We assessed the dosimetric parameters, treatment outcomes, and toxicity of IMRT in PMBCL. Forty-one PMBCL patients underwent mediastinal IMRT after doxorubicin-based chemotherapy. Thirty-eight patients had stage I-II disease, and 3 patients had stage III-IV disease. Most patients presented with bulky mediastinal disease (65.9%) and local [...]

Menée sur 97 patients atteints d'un cancer rectal récidivant localement (durée médiane de suivi : 51 mois), cette étude évalue, du point de vue des taux de contrôle de la maladie et du taux de survie globale à 5 ans, l'efficacité d'une radiothérapie intra-opératoire par électrons et identifie les facteurs pronostiques associés

Intraoperative Electron Radiation Therapy (IOERT) in the management of locally recurrent rectal cancer

Roeder, Falk ; Goetz, Joerg-Michael ; Habl, Gregor ; Bischof, Marc ; Krempien, Robert ; Buechler, Markus ; Hensley, Frank ; Huber, Peter ; Weitz, Juergen ; Debus, Juergen

BACKGROUND:To evaluate disease control, overall survival and prognostic factors in patients with locally recurrent rectal cancer after IOERT-containing multimodal therapy.METHODS:Between 1991 and 2006, 97 patients with locally recurrent rectal cancer have been treated with surgery and IOERT. IOERT was preceded or followed by external beam radiation therapy (EBRT) in 54 previously untreated patients (median dose 41.4 Gy) usually combined with 5-Fluouracil-based chemotherapy (89%). IOERT was [...]

A partir d'une revue systématique de la littérature (6 articles), cette méta-analyse évalue, du point de vue de la survie globale et par rapport à une chimiothérapie systémique, l'efficacité d'un traitement combinant résections chirurgicales et chimiothérapie hyperthermique intrapéritonéale pour traiter des métastases au niveau du péritoine et du foie chez des patients atteints d'un cancer colorectal

Cytoreductive surgery and HIPEC for peritoneal metastases combined with curative treatment of colorectal liver metastases: Systematic review of all literature and meta-analysis of observational studies

de Cuba, E. M. V. ; Kwakman, R. ; Knol, D. L. ; Bonjer, H. J. ; Meijer, G. A. ; te Velde, E. A.

Assess the overall outcome in colorectal cancer (CRC) patients that present with a combination of peritoneal metastases (PM) and liver metastases (CRLM) after curative resection and hyperthermic intraperitoneal chemotherapy (HIPEC) in the current literature. A systematic literature search according to the PRISMA guidelines was conducted using the PubMed database of the U.S. National library of Medicine using the keywords: colorectal cancer, liver metastasis, extra-hepatic, peritoneal [...]

Menée sur 30 patients atteints d'un méningiome affectant la vision (durée médiane de suivi : 28 mois), cette étude prospective observationnelle évalue, du point de vue des capacités visuelles et des événements indésirables, l'efficacité et la toxicité d'une radiothérapie avec modulation d'intensité

Meningioma Causing Visual Impairment: Outcomes and Toxicity After Intensity Modulated Radiation Therapy

Maclean, Jillian ; Fersht, Naomi ; Bremner, Fion ; Stacey, Chris ; Sivabalasingham, Suganya ; Short, Susan

To evaluate ophthalmologic outcomes and toxicity of intensity modulated radiation therapy (IMRT) in patients with meningiomas causing visual deficits. A prospective observational study with formal ophthalmologic and clinical assessment of 30 consecutive cases of meningioma affecting vision treated with IMRT from 2007 to 2011. Prescriptions were 50.4 Gy to mean target dose in 28 daily fractions. The median follow-up time was 28 months. Twenty-six meningiomas affected the anterior visual pathway [...]

Menée à l'aide de xénogreffes de tumeurs stromales gastro-intestinales, cette étude évalue l'activité antitumorale d'un composé appelé GDC-0941, un inhibiteur de la signalisation PI3K, seul ou en combinaison avec l'imatinib, en fonction du statut du gène PTEN

A potent combination of the novel PI3K inhibitor, GDC-0941, with imatinib in gastrointestinal stromal tumor xenografts: long-lasting responses after treatment withdrawal

Floris, Giuseppe ; Wozniak, Agnieszka ; Sciot, Raf ; Li, Haifu ; Friedman, Lori S. ; Van Looy, Thomas ; Wellens, Jasmien ; Vermaelen, Peter ; Deroose, Christophe M ; Fletcher, Jonathan A ; Debiec-Rychter, Maria ; Schöffski, Patrick

Introduction: Oncogenic signaling in gastrointestinal stromal tumors (GIST) is sustained via PI3K/AKT pathway. We used a panel of six GIST xenograft models to assess efficacy of GDC-0941 as single agent or in combination with imatinib (IMA). Experimental design: Nude mice (n=136) were grafted bilaterally with human GIST carrying divers KIT mutations. Mice were orally dosed over four weeks, grouped as follows: A) control; B) GDC-0941; C) IMA and D) GDC+IMA treatments. Xenografts re-growth after [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes de carcinome hépatocellulaire, cette étude suggère que le mécanisme d'action du dovetinib consiste à inhiber l'angiogenèse plutôt qu'à cibler directement les cellules cancéreuses

Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis

Chen, Zhi-Yuan ; Shi, Ming ; Peng, Li-Xia ; Wei, Wei ; Li, Xin-Jian ; Guo, Zhi-Xing ; Li, Shu-Hong ; Zhong, Chong ; Qian, Chao-Nan ; Guo, Rong-Ping

BACKGROUND:Dovitinib is a receptor tyrosine kinase (RTK) inhibitor targeting vascular endothelial growth factor receptors, fibroblast growth factor receptors and platelet-derived growth factor receptor beta. Dovitinib is currently in clinical trials for the treatment of hepatocellular carcinoma (HCC). METHOD:In this study, we used five HCC cell lines and five endothelial cell lines to validate molecular and cellular targets of dovitinib. RESULTS:Tumor growth and pulmonary metastasis were [...]

Cet article passe en revue les travaux récents sur la fonction de suppresseur de tumeurs attribuée à un sphingolipide, le céramide, et évalue les perspectives thérapeutiques offertes par le ciblage de mécanismes amplifiant cette fonction

Ceramide-orchestrated signalling in cancer cells

Morad, Samy A. F. ; Cabot, Myles C.

One crucial barrier to progress in the treatment of cancer has been the inability to control the balance between cell proliferation and apoptosis: enter ceramide. Discoveries over the past 15 years have elevated this sphingolipid to the lofty position of a regulator of cell fate. Ceramide, it turns out, is a powerful tumour suppressor, potentiating signalling events that drive apoptosis, autophagic responses and cell cycle arrest. However, defects in ceramide generation and metabolism in cancer [...]

Menée in vitro et in vivo, cette étude suggère que la privation de sérine représente une stratégie thérapeutique prometteuse pour les tumeurs dépourvues du gène p53

Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells

Maddocks, Oliver D. K. ; Berkers, Celia R. ; Mason, Susan M. ; Zheng, Liang ; Blyth, Karen ; Gottlieb, Eyal ; Vousden, Karen H.

Cancer cells acquire distinct metabolic adaptations to survive stress associated with tumour growth and to satisfy the anabolic demands of proliferation. The tumour suppressor protein p53 (also known as TP53) influences a range of cellular metabolic processes, including glycolysis oxidative phosphorylation, glutaminolysis and anti-oxidant response6. In contrast to its role in promoting apoptosis during DNA-damaging stress, p53 can promote cell survival during metabolic stress, a function that [...]

Menée à l'aide de modèles murins, cette étude suggère l'intérêt des inhibiteurs de MEK pour le traitement d'une leucémie myélomonocytaire juvénile ou chronique

Sustained MEK inhibition abrogates myeloproliferative disease in Nf1 mutant mice

Chang, Tiffany ; Krisman, Kimberly ; Theobald, Emily Harding ; Xu, Jin ; Akutagawa, Jon ; Lauchle, Jennifer O. ; Kogan, Scott ; Braun, Benjamin S. ; Shannon, Kevin

Children with neurofibromatosis type 1 (NF1) are predisposed to juvenile myelomonocytic leukemia (JMML), an aggressive myeloproliferative neoplasm (MPN) that is refractory to conventional chemotherapy. Conditional inactivation of the Nf1 tumor suppressor in hematopoietic cells of mice causes a progressive MPN that accurately models JMML and chronic myelomonocytic leukemia (CMML). We characterized the effects of Nf1 loss on immature hematopoietic populations and investigated treatment with the [...]

Menée in vitro et in vivo, cette étude suggère l'intérêt du sorafenib, seul ou en combinaison avec le bortezomib, pour le traitement d'un lymphome à cellules du manteau

Sorafenib inhibits cell migration and stroma-mediated bortezomib resistance by interfering B-cell receptor signaling and protein translation in mantle cell lymphoma

Xargay-Torrent, Silvia ; Lopez-Guerra, Monica ; Montraveta, Arnau ; Saborit-Villarroya, Ifigenia ; Rosich, Laia ; Navarro, Alba ; Perez-Galan, Patricia ; Roue, Gael ; Campo, Elias ; Colomer, Dolors

Purpose:We evaluated the antitumoral properties of the multikinase inhibitor sorafenib in mantle cell lymphoma (MCL), an aggressive B-lymphoma for which current therapies have shown limited efficacy. Experimental Design:Sensitivity to sorafenib was analyzed in MCL cell lines and primary samples in the context of BCR stimulation and microenvironment simulation. Sorafenib signaling was characterized by quantitative PCR, western blot, immunofluorescence and protein immunoprecipitation. Migration [...]

Menée sur des lignées cellulaires de lymphome hodgkinien classique, cette étude met en évidence l'activation de la signalisation NF-κB dans l'apparition d'une résistance à un inhibiteur de tyrosine kinase tel que le sorafenib ou le lestaurtinib

Induction of endoplasmic reticulum stress by sorafenib and activation of NF-κB by lestaurtinib as a novel resistance mechanism in Hodgkin lymphoma cell lines

Holz, Meike Stefanie ; Janning, Angela ; Renne, Christoph ; Gatttenlohner, Stefan ; Spieker, Tilmann ; Brauninger, Andreas

Hodgkin-Reed/Sternberg (HRS) cells of classical Hodgkin lymphoman (HL) show aberrant expression and activation of several receptor tyrosine kinases (RTKs) in the majority of cases. Therefore we tested whether tyrosine kinase inhibitors (TKIs) already in clinical use or late stages of clinical trials have antiproliferative effects on HRS cell lines and evaluated the targets, affected signaling pathways and mechanisms of cell death and resistance. Sorafenib and lestaurtinib had antiproliferative [...]

Menée à l'aide de techniques de criblage combinatoire à haut débit sur des lignées cellulaires de mélanome, cette étude identifie des combinaisons de molécules susceptibles d'être efficaces pour le traitement de mélanomes présentant des mutations activatrices des gènes RAS ou BRAF

Genotype-Selective Combination Therapies for Melanoma Identified by High-Throughput Drug Screening

Held, Matthew A. ; Langdon, Casey G. ; Platt, James T. ; Graham-Steed, Tisheeka ; Liu, Zongzhi ; Chakraborty, Ashok ; Bacchiocchi, Antonella ; Koo, Andrew ; Haskins, Jonathan W. ; Bosenberg, Marcus W. ; Stern, David F.

Resistance and partial responses to targeted monotherapy are major obstacles in cancer treatment. Systematic approaches to identify efficacious drug combinations for cancer are not well established, especially in the context of genotype. To address this, we have tested pairwise combinations of an array of small-molecule inhibitors on early-passage melanoma cultures using combinatorial drug screening. Results reveal several inhibitor combinations effective for melanomas with activating RAS or [...]

Menée sur des lignées cellulaires, cette étude suggère l'intérêt de composés à base d'indolocarbazole pour le traitement d'un cancer du poumon non à petites cellules présentant la mutation T790M du gène EGFR

Non-Covalent Wild-Type-Sparing Inhibitors of EGFR T790M

Lee, Ho-June ; Schaefer, Gabriele ; Heffron, Timothy P. ; Shao, Lily ; Ye, Xiaofen ; Sideris, Steve ; Malek, Shiva ; Chan, Emily ; Merchant, Mark ; La, Hank ; Ubhayakar, Savita ; Yauch, Robert L. ; Pirazzoli, Valentina ; Politi, Katerina ; Settleman, Jeff

Approximately half of EGFR mutant non-small cell lung cancer (NSCLC) patients treated with small molecule EGFR kinase inhibitors develop drug resistance associated with the EGFR T790M "gatekeeper" substitution, prompting efforts to develop covalent EGFR inhibitors, which can effectively suppress EGFR T790M in pre-clinical models. However, these inhibitors have yet to prove clinically efficacious, and their toxicity in skin, reflecting activity against wild-type EGFR, may limit dosing required [...]

Menée sur des lignées cellulaires et à l'aide d'un modèle murin de cancer du poumon, cette étude met en évidence l'intérêt de combiner un inhibiteur de la signalisation BCL-XL, le navitoclax, et un inhibiteur de MEK pour le traitement des cancers présentant des mutations du gène KRAS

Synthetic Lethal Interaction of Combined BCL-XL and MEK Inhibition Promotes Tumor Regressions in KRAS Mutant Cancer Models

Corcoran, Ryan B ; Cheng, Katherine A ; Hata, Aaron N ; Faber, Anthony C ; Ebi, Hiromichi ; Coffee, Erin M ; Greninger, Patricia ; Brown, Ronald D ; Godfrey, Jason T ; Cohoon, Travis J ; Song, Youngchul ; Lifshits, Eugene ; Hung, Kenneth E ; Shioda, Toshi ; Dias-Santagata, Dora ; Singh, Anurag ; Settleman, Jeffrey ; Benes, Cyril H ; Mino-Kenudson, Mari ; Wong, Kwok-Kin ; Engelman, Jeffrey A

KRAS is the most commonly mutated oncogene, yet no effective targeted therapies exist for KRAS mutant cancers. We developed a pooled shRNA-drug screen strategy to identify genes that, when inhibited, cooperate with MEK inhibitors to effectively treat KRAS mutant cancer cells. The anti-apoptotic BH3 family gene BCL-XL emerged as a top hit through this approach. ABT-263 (navitoclax), a chemical inhibitor that blocks the ability of BCL-XL to bind and inhibit pro-apoptotic proteins, in combination [...]

Menée in vitro et in vivo, cette étude met en évidence le rôle joué par le facteur de transcription Id-1 dans le processus invasif d'un glioblastome et suggère l'intérêt du cannabidiol pour inhiber son action

Id-1 is a Key Transcriptional Regulator of Glioblastoma Aggressiveness and a Novel Therapeutic Target

Soroceanu, Liliana ; Murase, Ryuichi ; Limbad, Chandani ; Singer, Eric L ; Allison, Juanita ; Adrados, Isabel ; Kawamura, Rumi ; Pakdel, Arash ; Fukuyo, Yayoi ; Nguyen, Daniel ; Khan, Sabeena ; Arauz, Robert ; Yount, Garret L ; Moore, Dan ; Desprez, Pierre-Yves ; McAllister, Sean D

Glioblastoma (GBM) is the most common form of primary adult brain tumors. A majority of GBMs grow invasively into distant brain tissue, leading to tumor recurrence, which is ultimately incurable. It is, therefore, essential to discover master regulators that control GBM invasiveness and target them therapeutically. We demonstrate here that the transcriptional regulator Id-1 plays a critical role in modulating the invasiveness of GBM cell lines and primary GBM cells. Id-1 expression levels [...]

Menée sur 663 patients atteints d'une leucémie lymphocytaire chronique, cette étude évalue, du point de vue de la survie sans progression et de la survie globale, plusieurs protocoles combinant chimiothérapie (chlorambucil, fludarabine) et immunothérapie (rituximab, alemtuzumab) en fonction de l'âge des patients

Impact of Age on Outcomes After Initial Therapy With Chemotherapy and Different Chemoimmunotherapy Regimens in Patients With Chronic Lymphocytic Leukemia: Results of Sequential Cancer and Leukemia Group B Studies

Woyach, Jennifer A. ; Ruppert, Amy S. ; Rai, Kanti ; Lin, Thomas S. ; Geyer, Susan ; Kolitz, Jonathan ; Appelbaum, Frederick R. ; Tallman, Martin S. ; Belch, Andrew R. ; Morrison, Vicki A. ; Larson, Richard A. ; Byrd, John C.

Purpose Chronic lymphocytic leukemia (CLL) is a disease of the elderly, yet few clinical trials include a significant number of older patients, and outcomes after specific therapies can be different depending on age. Patients And methods We examined patients enrolled onto successive first-line CALGB CLL trials to determine whether efficacy of regimens varied by age, focusing on ideal chemotherapy choice and benefit of immunotherapy addition to chemotherapy in older patients. Regimens included [...]

Mené sur 14 patients atteints d'un mélanome de stade avancé, cet essai de phase II évalue, du point de vue de critères RECIST, un inhibiteur de farnésyltransférase (R115777)

Phase II study of the farnesyltransferase inhibitor R115777 in advanced melanoma (CALGB 500104)

Gajewski, Thomas ; Salama, April ; Niedzwiecki, Donna ; Johnson, Jeffrey ; Linette, Gerald ; Bucher, Cynthia ; Blaskovich, Michelle ; Sebti, Said ; Haluska, Frank

BACKGROUND:Multiple farnesylated proteins are involved in signal transduction in cancer. Farnesyltransferase inhibitors (FTIs) have been developed as a strategy to inhibit the function of these proteins. As FTIs inhibit proliferation of melanoma cell lines, we undertook a study to assess the impact of a FTI in advanced melanoma. As farnesylated proteins are also important for T cell activation, measurement of effects on T cell function was also pursued. METHODS:A 3-stage trial design was [...]

Mené sur 38 patients atteints d'un myélome multiple récidivant et réfractaire au lénalidomide et au bortezomib, cet essai de phase I évalue la dose maximale tolérée du pomalidomide par voie orale, avec ou sans dexaméthasone

Phase I study of pomalidomide MTD, safety and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib

Richardson, Paul G. ; Siegel, David ; Baz, Rachid ; Kelley, Susan L. ; Munshi, Nikhil C. ; Laubach, Jacob ; Sullivan, Daniel ; Alsina, Melissa ; Schlossman, Robert ; Ghobrial, Irene M. ; Doss, Deborah ; Loughney, Nora ; McBride, Laura ; Bilotti, Elizabeth ; Anand, Palka ; Nardelli, Lisa ; Wear, Sandra ; Larkins, Gail ; Chen, Min ; Zaki, Mohamad ; Jacques, Christian ; Anderson, Kenneth C.

This phase 1 dose-escalation study determined the maximum tolerated dose (MTD) of oral pomalidomide (4 dose levels) administered on days 1 to 21 of each 28-day cycle in patients with relapsed and refractory multiple myeloma (RRMM). After 4 cycles, patients who progressed or had not achieved minimal response (serum and urine M-protein reduction of ≥ 25% and ≥ 50%) could receive dexamethasone, 40 mg/week. Safety and efficacy were evaluated. Thirty-eight patients who had received both bortezomib [...]

Menée sur une cohorte de 438 patientes atteintes d'une tumeur trophoblastique gestationnelle entre 1995 et 2010, cette étude rétrospective évalue la survie globale associée à un protocole thérapeutique EMA/CO et la compare à la survie observée dans une cohorte traitée entre 1979 et 1995

EMA/CO for High-Risk Gestational Trophoblastic Neoplasia: Good Outcomes With Induction Low-Dose Etoposide-Cisplatin and Genetic Analysis

Alifrangis, Constantine ; Agarwal, Roshan ; Short, Delia ; Fisher, Rosemary A. ; Sebire, Neil J. ; Harvey, Richard ; Savage, Philip M. ; Seckl, Michael J.

Purpose Patients with high-risk (International Federation of Gynecology and Obstetrics score ≥ 7) gestational trophoblastic neoplasia (GTN) frequently receive etoposide, methotrexate, and dactinomycin alternating weekly with cyclophosphamide and vincristine (EMA/CO). Between 1979 and 1995, overall survival (OS) with this regimen at our institute was 85.4% with a significant proportion of early deaths (< 4 weeks). Here, we determine whether survival rates have improved in a more recent patient [...]

Menée sur 2 673 patients atteints d'un cancer du côlon de stade 2-3 (durée médiane de suivi : 5 ans), cette étude évalue, du point de vue de la survie sans maladie et de la survie globale, l'ajout de bevacizumab pendant un an à un protocole FOLFOX6

Bevacizumab in Stage II-III Colon Cancer: 5-Year Update of the National Surgical Adjuvant Breast and Bowel Project C-08 Trial

Allegra, Carmen J. ; Yothers, Greg ; O'Connell, Michael J. ; Sharif, Saima ; Petrelli, Nicholas J. ; Lopa, Samia H. ; Wolmark, Norman

Purpose The National Surgical Adjuvant Breast and Bowel Project trial C-08 was designed to investigate the safety and efficacy of adding bevacizumab to fluorouracil, leucovorin, and oxaliplatin (FOLFOX6) for the adjuvant treatment of patients with stage 2–3 colon cancer. Our report summarizes the primary and secondary end points of disease-free and overall survival, respectively, with 5 years median follow-up time. Patients And methods Patients received modified FOLFOX6 once every 2 weeks for a [...]

Mené sur 1 491 patientes atteintes d'un cancer du sein de stade précoce avec envahissement ganglionnaire (durée médiane de suivi : 124 mois), cet essai de phase III compare, du point de vue de la survie sans progression, deux traitements adjuvants (docétaxel, doxorubicine et cyclophosphamide - fluorouracile, doxorubicine et cyclophosphamide)

Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial

Mackey, John R. ; Martin, Miguel ; Pienkowski, Tadeusz ; Rolski, Janusz ; Guastalla, Jean-Paul ; Sami, Amer ; Glaspy, John ; Juhos, Eva ; Wardley, Andrew ; Fornander, Tommy ; Hainsworth, John ; Coleman, Robert ; Modiano, Manuel R. ; Vinholes, Jeferson ; Pintér, Tamás ; Rodríguez-Lescure, Álvaro ; Colwell, Bruce ; Whitlock, Pierre ; Provencher, Louise ; Laing, Kara ; Walde, David ; Price, Chris ; Hugh, Judith C. ; Childs, Barrett H. ; Bassi, Kimberly ; Lindsay, Mary-Ann ; Wilson, Véronique ; Rupin, Matthieu ; Houé, Vincent ; Vogel, Charles

Background : We compared standard adjuvant anthracycline chemotherapy with anthracycline-taxane combination chemotherapy in women with operable node-positive breast cancer. Here we report the final, 10-year follow-up analysis of disease-free survival, overall survival, and long-term safety. Methods : BCIRG 001 was an open label, phase 3, multicentre trial in which 1491 patients aged 18-70 years with node-positive, early breast cancer and a Karnofsky score of 80% or more were randomly assigned [...]

Mené sur 31 patientes atteintes d'un cancer du sein HER2-, cet essai de phase II évalue, du point de vue de la mesure de l'inhibition de la prolifération cellulaire à l'aide de Ki67, le lapatinib en traitement pré-opératoire

An open-label study of lapatinib in women with HER-2-negative early breast cancer: the lapatinib pre-surgical study (LPS study)

Coombes, R. C. ; Tat, T. ; Miller, M. L. ; Reise, J. A. ; Mansi, J. L. ; Hadjiminas, D. J. ; Shousha, S. ; Elsheikh, S. E. ; Lam, E. W-F. ; Horimoto, Y. ; El-Bahrawy, M. ; Aboagye, E. O. ; Contractor, K. B. ; Shaw, J. A. ; Walker, R. A. ; Marconell, M. H. ; Palmieri, C. ; Stebbing, J.

Background This phase II, open-label, multicentre study aimed to evaluate changes in cell proliferation and biomarkers, as well as efficacy of lapatinib in treatment-naïve patients with HER-2-negative primary breast cancer. Patients and methods Patients received 1500 mg lapatinib for 28–42 days before surgery with repeat biopsies and measurements. The primary end point was inhibition of cell proliferation measured by Ki67; the secondary end points included clinical response, adverse events and [...]

Cet article présente un cadre d'analyse de l'inclusion des patients à un essai clinique et l'illustre sur un exemple d'essai dans le cancer de la prostate

Removing barriers to participation in clinical trials, a conceptual framework and retrospective chart review study

Kanarek, Norma ; Kanarek, Marty ; Olatoye, Dare ; Carducci, Michael

BACKGROUND:Enrollment in interventional therapeutic clinical trials is a small fraction of all patients who might participate given reasonable access. METHODS:A hierarchical approach is utilized in measuring staged participation from trial availability to patient enrollment. Our framework suggests that concern for justice comes in the design and eligibility criteria for clinical trials; attention to beneficence is given in the eligibility and physician triage stages. The remaining four stages [...]

Cet article passe en revue les perspectives offertes par la recherche translationnelle pour la découverte de nouveaux médicaments

Translational research: the changing landscape of drug discovery

Fishburn, C. Simone

Drug discovery represents the first step in the creation of new drugs, and takes place in academic institutions, biotech companies, and large pharmaceutical corporations. Until recently, these sectors have each operated independently with little collaboration between those at the forefront of discovery research and those with experience in developing drugs. With the rise of translational research these relationships are shifting and new hubs are emerging, because key players seek to pool the [...]