Menée sur 1 302 patients atteints d'un cancer localisé de la prostate traité par radiothérapie externe ou prostatectomie radicale, cette étude évalue, du point de vue de la survie sans métastases et de la survie spécifique à 3, 5 et 10 ans, la réponse au traitement en fonction de la présence ou non d'une mutation des gènes BRCA dans les cellules de la lignée germinale

Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer

Castro, Elena ; Goh, Chee ; Leongamornlert, Daniel ; Saunders, Ed ; Tymrakiewicz, Malgorzata ; Dadaev, Tokhir ; Govindasami, Koveela ; Guy, Michelle ; Ellis, Steve ; Frost, Debra ; Bancroft, Elizabeth ; Cole, Trevor ; Tischkowitz, Marc ; Kennedy, M. John ; Eason, Jacqueline ; Brewer, Carole ; Evans, D. Gareth ; Davidson, Rosemarie ; Eccles, Diana ; Porteous, Mary E. ; Douglas, Fiona ; Adlard, Julian ; Donaldson, Alan ; Antoniou, Antonis C. ; Kote-Jarai, Zsofia ; Easton, Douglas F. ; Olmos, David ; Eeles, Rosalind

Background : Germline BRCA mutations are associated with worse prostate cancer (PCa) outcomes; however, the most appropriate management for mutation carriers has not yet been investigated. Objective : To evaluate the response of BRCA carriers to conventional treatments for localised PCa by analysing metastasis-free survival (MFS) and cause-specific survival (CSS) following radical prostatectomy (RP) or external-beam radiation therapy (RT). Design, setting, and participants : Tumour features and [...]

Menée sur 167 patientes atteintes d'un cancer invasif du sein de stade T1 ou T2 et traitées par chirurgie conservatrice (âge : de 26 à 45 ans ; durée médiane de suivi : 92 mois), cette étude évalue l'efficacité, du point de vue du taux de contrôle local, et les effets indésirables d'une curiethérapie à haut débit de dose de type "boost"

High-Dose-Rate Brachytherapy Boost Effect on Local Tumor Control in Young Women With Breast Cancer

Guinot, Jose-Luis ; Baixauli-Perez, Cristobal ; Soler, Pablo ; Tortajada, Maria Isabel ; Moreno, Araceli ; Santos, Miguel Angel ; Mut, Alejandro ; Gozalbo, Francisco ; Arribas, Leoncio

Purpose : To evaluate the local control rate and complications of a single fraction of high-dose-rate brachytherapy (HDR BT) boost in women aged 45 yeas and younger after breast-conserving therapy. Methods and Materials : Between 1999 and 2007, 167 patients between the ages of 26 and 45 years old (72 were 40 years old or younger), with stages T1 to T2 invasive breast cancer with disease-free margin status of at least 5 mm after breast-conserving surgery received 46 to 50 Gy whole-breast [...]

Mené sur 12 patientes présentant des métastases cérébrales ayant pour origine un cancer du sein, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, et les effets secondaires de la capécitabine en combinaison avec une radiothérapie concomitante du cerveau entier puis le sunitinib

A Phase II Trial of Capecitabine Concomitantly With Whole-Brain Radiotherapy Followed by Capecitabine and Sunitinib for Brain Metastases From Breast Cancer

Niravath, Polly ; Tham, Yee Lu ; Wang, Tao ; Rodriguez, Angel ; Foreman, Claudette ; Hilsenbeck, Susan G. ; Elledge, Richard ; Rimawi, Mothaffar

Background : Brain metastasis from breast cancer presents a significant threat to women’s health and quality of life. Capecitabine and sunitinib have shown some activity in this setting; therefore, we conducted a single-arm phase II trial with these agents. Methods : Patients with breast cancer and central nervous system (CNS) metastases received whole-brain radiotherapy concurrently with capecitabine (1,000 mg/m2 per day for 14 consecutive days), followed by concomitant capecitabine (2,000 [...]

Menée sur des lignées cellulaires, à l'aide de modèles murins et sur 3 patients atteints d'une tumeur stromale gastro-intestinale réfractaire à l'imatinib, au sunitinib et au regorafenib, cette étude évalue l'activité antitumorale du ponatinib

Ponatinib Inhibits Polyclonal Drug-Resistant KIT Oncoproteins and Shows Therapeutic Potential in Heavily Pretreated Gastrointestinal Stromal Tumor (GIST) Patients

Garner, Andrew P. ; Gozgit, Joseph M. ; Anjum, Rana ; Vodala, Sadanand ; Schrock, Alexa ; Zhou, Tianjun ; Serrano, Cesar ; Eilers, Grant ; Zhu, Meijun ; Ketzer, Julia ; Wardwell, Scott ; Ning, Yaoyu ; Song, Youngchul ; Kohlmann, Anna ; Wang, Frank ; Clackson, Tim ; Heinrich, Michael C. ; Fletcher, Jonathan A. ; Bauer, Sebastian ; Rivera, Victor M.

Purpose: KIT is the major oncogenic driver of gastrointestinal stromal tumors (GIST). Imatinib, sunitinib, and regorafenib are approved therapies; however, efficacy is often limited by the acquisition of polyclonal secondary resistance mutations in KIT, with those located in the activation (A) loop (exons 17/18) being particularly problematic. Here, we explore the KIT-inhibitory activity of ponatinib in preclinical models and describe initial characterization of its activity in patients with [...]

Menée in vitro et in vivo à l'aide d'une technique d'imagerie cellulaire, cette étude met en évidence le rôle joué par la protéine MDR1 dans la résistance à l'éribuline

Single-cell pharmacokinetic imaging reveals a therapeutic strategy to overcome drug resistance to the microtubule inhibitor eribulin

Laughney, Ashley M. ; Kim, Eunha ; Sprachman, Melissa M. ; Miller, Miles A. ; Kohler, Rainer H. ; Yang, Katy S. ; Orth, James D. ; Mitchison, Timothy J. ; Weissleder, Ralph

Eribulin mesylate was developed as a potent microtubule-targeting cytotoxic agent to treat taxane-resistant cancers, but recent clinical trials have shown that it eventually fails in many patient subpopulations for unclear reasons. To investigate its resistance mechanisms, we developed a fluorescent analog of eribulin with pharmacokinetic (PK) properties and cytotoxic activity across a human cell line panel that are sufficiently similar to the parent drug to study its cellular PK and tissue [...]

Cet article passe en revue les travaux récents suggérant l'intérêt de combiner une immunothérapie avec des inhibiteurs de BRAF et MEK pour le traitement des patients atteints d'un mélanome présentant un gène BRAF muté

Effects of BRAF Mutations and BRAF Inhibition on Immune Responses to Melanoma

Ilieva, Kristina M. ; Correa, Isabel ; Josephs, Debra H. ; Karagiannis, Panagiotis ; Egbuniwe, Isioma U. ; Cafferkey, Michiala J. ; Spicer, James F. ; Harries, Mark ; Nestle, Frank O. ; Lacy, Katie E. ; Karagiannis, Sophia N.

Malignant melanoma is associated with poor clinical prognosis; however, novel molecular and immune therapies are now improving patient outcomes. Almost 50% of melanomas harbor targetable activating mutations of BRAF that promote RAS–RAF–MEK–ERK pathway activation and melanoma proliferation. Recent evidence also indicates that melanomas bearing mutant BRAF may also have altered immune responses, suggesting additional avenues for treatment of this patient group. The small molecule inhibitors [...]

Cet article passe en revue les perspectives offertes par le développement de nouveaux traitements pour les patients atteints d'un mésothéliome pleural malin

Malignant Pleural Mesothelioma: new hope in the horizon with novel therapeutic strategies

Remon, J. ; Reguart, N. ; Corral, J. ; Lianes, P.

Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy of the pleura, with a strong causal link to asbestos exposure. MPM incidence has been increasing in recent years and it is not expected to fall off in the next two decades. Prognosis of MPM patients is modest since the vast majority of patients are diagnosed at advanced stage and because platinum-based chemotherapy remains the cornerstone of treatment, with no standard second line treatment. Most current efforts to improve [...]

Menée in vitro et in vivo, cette étude évalue l'activité antitumorale de l'alectinib, un inhibiteur d'ALK, pour le traitement d'un cancer du poumon non à petites cellules présentant un réarrangement du gène RET

Alectinib shows potent antitumor activity against RET-rearranged non-small cell lung cancer

Kodama, Tatsushi ; Tsukaguchi, Toshiyuki ; Satoh, Yasuko ; Yoshida, Miyuki ; Watanabe, Yoshiaki ; Kondoh, Osamu ; Sakamoto, Hiroshi

Alectinib/CH5424802 is a known inhibitor of anaplastic lymphoma kinase (ALK) and is being evaluated in clinical trials for the treatment of ALK fusion-positive non-small cell lung cancer (NSCLC). Recently, some RET and ROS1 fusion genes have been implicated as driver oncogenes in NSCLC and have become molecular targets for antitumor agents. This study aims to explore additional target indications of alectinib by testing its ability to inhibit the activity of kinases other than ALK. We newly [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en induisant l'activation du gène NCoA2, un traitement anti-androgénique favorise le processus métastatique d'un cancer de la prostate et l'apparition d'une résistance à la castration

Androgen deprivation–induced NCoA2 promotes metastatic and castration-resistant prostate cancer

Qin, Jun ; Lee, Hui-Ju ; Wu, San-Pin ; Lin, Shih-Chieh ; Lanz, Rainer B. ; Creighton, Chad J. ; DeMayo, Francesco J. ; Tsai, Sophia Y. ; Tsai, Ming-Jer

A major clinical hurdle for the management of advanced prostate cancer (PCa) in patients is the resistance of tumors to androgen deprivation therapy (ADT) and their subsequent development into castration-resistant prostate cancer (CRPC). While recent studies have identified potential pathways involved in CRPC development, the drivers of CRPC remain largely undefined. Here we determined that nuclear receptor coactivator 2 (NCoA2, also known as SRC-2), which is frequently amplified or [...]

Menée à l'aide de divers modèles murins, cette étude suggère l'intérêt d'un traitement combinant inhibiteurs de PI3K/mTOR et d'EGFR pour les patients atteints d'un cancer colorectal présentant un gène KRAS muté

Resistance to dual blockade of the kinases PI3K and mTOR in KRAS-mutant colorectal cancer models results in combined sensitivity to inhibition of the receptor tyrosine kinase EGFR

Belmont, Peter J. ; Jiang, Ping ; McKee, Trevor D. ; Xie, Tao ; Isaacson, Jason ; Baryla, Nicole E. ; Roper, Jatin ; Sinnamon, Mark J. ; Lee, Nathan V. ; Kan, Julie L. C. ; Guicherit, Oivin ; Wouters, Bradly G. ; O’Brien, Catherine A. ; Shields, David ; Olson, Peter ; VanArsdale, Todd ; Weinrich, Scott L. ; Rejto, Paul ; Christensen, James G. ; Fantin, Valeria R. ; Hung, Kenneth E. ; Martin, Eric S.

Targeted blockade of aberrantly activated signaling pathways is an attractive therapeutic strategy for solid tumors, but drug resistance is common. KRAS is a frequently mutated gene in human cancer but remains a challenging clinical target. Inhibitors against KRAS signaling mediators, namely, PI3K (phosphatidylinositol 3-kinase) and mTOR (mechanistic target of rapamycin), have limited clinical efficacy as single agents in KRAS-mutant colorectal cancer (CRC). We investigated potential bypass [...]

Menée à l'aide de modèles murins, cette étude évalue l'efficacité d'une administration intrapleurale d'un traitement à base de lymphocytes T portant un récepteur antigénique chimérique dirigé contre la mésothéline pour le traitement d’une tumeur de la plèvre

Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity

Adusumilli, Prasad S. ; Cherkassky, Leonid ; Villena-Vargas, Jonathan ; Colovos, Christos ; Servais, Elliot ; Plotkin, Jason ; Jones, David R. ; Sadelain, Michel

Translating the recent success of chimeric antigen receptor (CAR) T cell therapy for hematological malignancies to solid tumors will necessitate overcoming several obstacles, including inefficient T cell tumor infiltration and insufficient functional persistence. Taking advantage of an orthotopic model that faithfully mimics human pleural malignancy, we evaluated two routes of administration of mesothelin-targeted T cells using the M28z CAR. We found that intrapleurally administered CAR T cells [...]

Menée à l'aide d'une technique d'imagerie intravitale sur un modèle murin de cancer métastatique du sein, cette étude met en évidence, dans le micro-environnement tumoral, les effets d'une thérapie ciblée sur CSF-1R

Intravital imaging reveals distinct responses of depleting dynamic tumor-associated macrophage and dendritic cell subpopulations

Lohela, Marja ; Casbon, Amy-Jo ; Olow, Aleksandra ; Bonham, Lynn ; Branstetter, Daniel ; Weng, Ning ; Smith, Jeffrey ; Werb, Zena

Tumor-infiltrating inflammatory cells comprise a major part of the stromal microenvironment and support cancer progression by multiple mechanisms. High numbers of tumor myeloid cells correlate with poor prognosis in breast cancer and are coupled with the angiogenic switch and malignant progression. However, the specific roles and regulation of heterogeneous tumor myeloid populations are incompletely understood. CSF-1 is a major myeloid cell mitogen, and signaling through its receptor CSF-1R is [...]

Menée in vitro et in vivo, cette étude suggère l'intérêt d'une stratégie basée sur l'inhibition de CDK7 pour le traitement de patients atteints d'un neuroblastome avec amplification de MYCN

CDK7 Inhibition Suppresses Super-Enhancer-Linked Oncogenic Transcription in MYCN-Driven Cancer

Chipumuro, Edmond ; Marco, Eugenio ; Christensen, Camilla L ; Kwiatkowski, Nicholas ; Zhang, Tinghu ; Hatheway, Clark M ; Abraham, Brian J ; Sharma, Bandana ; Yeung, Caleb ; Altabef, Abigail ; Perez-Atayde, Antonio ; Wong, Kwok-Kin ; Yuan, Guo-Cheng ; Gray, Nathanael S ; Young, Richard A ; George, Rani E

The MYC oncoproteins are thought to stimulate tumor cell growth and proliferation through amplification of gene transcription, a mechanism that has thwarted most efforts to inhibit MYC function as potential cancer therapy. Using a covalent inhibitor of cyclin-dependent kinase 7 (CDK7) to disrupt the transcription of amplified MYCN in neuroblastoma cells, we demonstrate downregulation of the oncoprotein with consequent massive suppression of MYCN-driven global transcriptional amplification. This [...]

Mené sur 23 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue la dose maximale tolérée et l'activité clinique d'un composé appelé PF-04449913, un inhibiteur de la signalisation Hedgehog

A Phase I Study of PF-04449913, an Oral Hedgehog Inhibitor, in Patients with Advanced Solid Tumors

Wagner, Andrew J ; Messersmith, Wells A. ; Shaik, M. Naveed ; Li, Sherry ; Zheng, Xianxian ; McLachlan, Karen R ; Cesari, Rossano ; Courtney, Rachel ; Levin, Wendy J ; El-Khoueiry, Anthony B.

Purpose: To estimate the maximum tolerated dose (MTD) of single-agent PF-04449913, and to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity in patients with advanced tumors. Experimental Design: A 3+3 design was used in this open-label, multicenter, phase I study and dose escalation/de-escalation applied until identification of the MTD. PF-04449913 was orally administered once daily (QD) in continuous 28-day treatment cycles. The starting dose [...]

Mené sur 54 patients atteints d'une tumeur solide exprimant Fn14, cet essai de phase I évalue la dose maximale tolérée et l'activité antitumorale d'un composé appelé RG7212, un anticorps monoclonal ciblant la signalisation TWEAK

A Phase I Monotherapy Study of RG7212, a First-in-Class Monoclonal Antibody Targeting TWEAK Signaling in Patients With Advanced Cancers

Lassen, Ulrik ; Meulendijks, Didier ; Siu, Lillian L ; Karanikas, Vaios ; Mau-Sorensen, Morten ; Schellens, Jan H.M. ; Hansen, Aaron ; Jonker, Derek ; Simcox, Mary Ellen ; Schostack, Kathleen ; Bottino, Dean ; Zhong, Hua ; Roessler, Markus ; Vega-Harring, Suzana ; Jarutat, Tiantom ; Geho, David ; Wang, Ka ; DeMario, Mark ; Goss, Glenwood

Purpose : Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible molecule 14 (Fn14) are a ligand-receptor pair frequently overexpressed in solid tumors. TWEAK:Fn14 signaling regulates multiple oncogenic processes through MAPK, AKT, and NFκB pathway activation. A phase I study of RG7212, a humanized anti-TWEAK IgG1κ monoclonal antibody, was conducted in patients with advanced solid tumors expressing Fn14. Methods : Dose escalations, over a 200- [...]

Mené sur 36 patients atteints d'une leucémie lymphoblastique aiguë récidivante ou réfractaire (âge médian : 32 ans), cet essai de phase II évalue l'efficacité, du point de vue de la rémission complète, et la toxicité du blinatumomab

Phase II Trial of the Anti-CD19 Bispecific T Cell–Engager Blinatumomab Shows Hematologic and Molecular Remissions in Patients With Relapsed or Refractory B-Precursor Acute Lymphoblastic Leukemia

Topp, Max S. ; Gökbuget, Nicola ; Zugmaier, Gerhard ; Klappers, Petra ; Stelljes, Matthias ; Neumann, Svenja ; Viardot, Andreas ; Marks, Reinhard ; Diedrich, Helmut ; Faul, Christoph ; Reichle, Albrecht ; Horst, Heinz-August ; Brüggemann, Monika ; Wessiepe, Dorothea ; Holland, Chris ; Alekar, Shilpa ; Mergen, Noemi ; Einsele, Hermann ; Hoelzer, Dieter ; Bargou, Ralf C.

Purpose : Patients with relapsed or refractory acute lymphoblastic leukemia (ALL) have a dismal prognosis. CD19 is homogenously expressed in B-precursor ALL and can be targeted by the investigational bispecific T cell–engager antibody blinatumomab. A phase II trial was performed to determine clinical activity in this patient cohort. Patients and Methods : Thirty-six patients with relapsed or refractory B-precursor ALL were treated with blinatumomab in cycles of 4-week continuous infusion [...]

Mené sur 637 patients atteints d'un cancer du poumon à petites cellules, cet essai randomisé de phase III compare l'efficacité, du point de vue de la survie globale, et la toxicité de l'amrubicine et du topotecan en traitement de deuxième ligne

Randomized Phase III Trial of Amrubicin Versus Topotecan As Second-Line Treatment for Patients With Small-Cell Lung Cancer

von Pawel, Joachim ; Jotte, Robert ; Spigel, David R. ; O'Brien, Mary E.R. ; Socinski, Mark A. ; Mezger, Jörg ; Steins, Martin ; Bosquée, Léon ; Bubis, Jeffrey ; Nackaerts, Kristiaan ; Trigo, José M. ; Clingan, Philip ; Schütte, Wolfgang ; Lorigan, Paul ; Reck, Martin ; Dómine, Manuel ; Shepherd, Frances A. ; Li, Shaoyi ; Renschler, Markus F.

Purpose : Amrubicin, a third-generation anthracycline and potent topoisomerase II inhibitor, showed promising activity in small-cell lung cancer (SCLC) in phase II trials. This phase III trial compared the safety and efficacy of amrubicin versus topotecan as second-line treatment for SCLC. Patients and Methods : A total of 637 patients with refractory or sensitive SCLC were randomly assigned at a ratio of 2:1 to 21-day cycles of amrubicin 40 mg/m2 intravenously (IV) on days 1 to 3 or topotecan [...]

Mené sur 140 patients atteints d'un cancer du poumon non à petites cellules de stade avancé ou métastatique, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout de ramucirumab à un traitement combinant pemetrexed et sels de platine (carboplatine ou cisplatine)

Phase 2, randomized, open-label study of ramucirumab in combination with first-line pemetrexed and platinum chemotherapy in patients with nonsquamous, advanced/metastatic non–small cell lung cancer

Doebele, Robert C. ; Spigel, David ; Tehfe, Mustapha ; Thomas, Sachdev ; Reck, Martin ; Verma, Sunil ; Eakle, Janice ; Bustin, Frederique ; Goldschmidt, Jerome ; Cao, Dachuang ; Alexandris, Ekaterine ; Yurasov, Sergey ; Camidge, D. Ross ; Bonomi, Philip

BACKGROUND : Vascular endothelial growth factor (VEGF)–mediated angiogenesis plays an important role in non–small cell lung cancer (NSCLC). Ramucirumab is a human immunoglobulin G1 monoclonal antibody that inhibits VEGF receptor 2. This phase 2 study investigated ramucirumab in combination with first-line pemetrexed and platinum chemotherapy in advanced/metastatic NSCLC. METHODS : Eligible stage IV nonsquamous NSCLC patients with no prior chemotherapy for metastatic disease were randomized 1:1 [...]

Menée sur 30 patients présentant des métastases hépatiques diagnostiquées entre 1993 et 2010 et ayant pour origine un carcinome rhinopharyngé traité avec succès par radiothérapie radicale en combinaison ou non avec une chimiothérapie adjuvante, cette étude chinoise évalue, en termes de survie et par rapport à une chimio-embolisation transartérielle, le bénéfice d'une hépatectomie partielle

Partial hepatectomy for liver metastases from nasopharyngeal carcinoma: a comparative study and review of the literature

Huang, Jun ; Li, Qijiong ; Zheng, Yun ; Shen, Jingxian ; Li, Binkui ; Zou, Ruhai ; Wang, Jianping ; Yuan, Yunfei

Background : The management of liver metastases from nasopharyngeal carcinoma (NPC) has not been extensively investigated. This study aimed to compare the long-term outcome of patients with liver metastases from NPC who were treated by a partial hepatectomy or transcatheter hepatic artery chemoembolization (TACE). Methods : Between January 1993 and December 2010, 830 patients were diagnosed with liver metastases from NPC and exhibited a complete response to the primary cancer of the nasopharynx [...]

Mené sur 48 patients atteints d'un cancer du poumon non à petites cellules de stade III (durée médiane de suivi : 54 mois), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse, et la toxicité d'un traitement comportant une chimiothérapie par cisplatine-S-1 (tégafur, giméracil et otéracil potassium) en combinaison avec une radiothérapie thoracique concomitante

A phase II study of cisplatin plus S-1 with concurrent thoracic radiotherapy for locally advanced non-small-cell lung cancer: the Okayama Lung Cancer Study Group Trial 0501

Nogami, Naoyuki ; Takigawa, Nagio ; Hotta, Katsuyuki ; Segawa, Yoshihiko ; Kato, Yuka ; Kozuki, Toshiyuki ; Oze, Isao ; Kishino, Daizo ; Aoe, Keisuke ; Ueoka, Hiroshi ; Kuyama, Shoichi ; Harita, Shingo ; Okada, Toshiaki ; Hosokawa, Shinobu ; Inoue, Koji ; Gemba, Kenichi ; Shibayama, Takuo ; Tabata, Masahiro ; Takemoto, Mitsuhiro ; Kanazawa, Susumu ; Tanimoto, Mitsune ; Kiura, Katsuyuki

Background : Although cisplatin-based chemotherapy combined with thoracic irradiation (TRT) is a standard treatment for unresectable, locally advanced non-small cell lung cancer (NSCLC), this treatment outcome has remained unsatisfactory. We had previously conducted a phase I trial of cisplatin plus S-1, an oral 5-fluorouracil derivative, and TRT, which were safe and effective. Methods : In this phase II trial, 48 patients with stage III NSCLC received cisplatin (40 mg/m2 on days 1, 8, 29 and [...]

Menée à partir de données portant sur 2 115 patients traités par résection et chimiothérapie pour un cancer du poumon non à petites cellules avec envahissement ganglionnaire (stade pN2) diagnostiqué entre 2004 et 2006, cette étude évalue, du point de vue de la survie globale, l'intérêt d'une radiothérapie post-opératoire

Post-Operative Radiotherapy (PORT) is Associated with Better Survival in Non-Small Cell Lung Cancer with Involved N2 Lymph Nodes: Results of an Analysis of the National Cancer Data Base

Mikell, John L. ; Gillespie, Theresa W. ; Hall, William A. ; Nickleach, Dana C. ; Liu, Yuan ; Lipscomb, Joseph ; Ramalingam, Suresh S. ; Rajpara, Raj S. ; Force, Seth D. ; Fernandez, Felix G. ; Owonikoko, Taofeek K. ; Pillai, Rathi N. ; Khuri, Fadlo R. ; Curran, Walter J. ; Higgins, Kristin A.

Introduction : Use of post-operative radiotherapy (PORT) in non-small cell lung cancer (NSCLC) remains controversial. Limited data indicate that PORT may benefit patients with involved N2 nodes. This study evaluates this hypothesis in a large retrospective cohort treated with chemotherapy and contemporary radiation techniques. Methods : The National Cancer Data Base (NCDB) was queried for patients diagnosed 2004-2006 with resected NSCLC and pathologically involved N2 (pN2) nodes also treated [...]

Mené sur 78 patients atteints d'un cancer du poumon non à petites cellules de stade III, non résécable et de pronostic défavorable (âge médian : 68 ans), cet essai de phase II évalue, du point de vue du taux de réponse globale, du taux de contrôle de la maladie et du taux de survie globale à 1 an, l'efficacité d'un traitement comportant une chimiothérapie d'induction par carboplatine-nab-paclitaxel puis une radiothérapie thoracique en combinaison avec l'erlotinib

A phase II study of induction chemotherapy followed by thoracic radiotherapy and erlotinib in poor risk stage III non-small cell lung cancer: Results of CALGB 30605 (Alliance)/RTOG 0972 (NRG)

Lilenbaum, Rogerio ; Samuels, Michael ; Wang, Xiaofei ; Kong, Feng Ming ; Jänne, Pasi A. ; Masters, Gregory ; Katragadda, Sreedhar ; Hodgson, Lydia ; Bogart, Jeffrey ; Bradley, Jeffrey ; Vokes, Everett

Introduction : Patients with stage III non-small cell lung cancer (NSCLC) and poor performance status (PS) and/or weight loss (WL) do not seem to benefit from standard therapy. Based on the pre-clinical interaction between epidermal growth factor receptor (EGFR) inhibitors and radiation, we designed a trial of induction chemotherapy followed by thoracic radiotherapy (TRT) and concurrent erlotinib. Methods : Patients with poor risk unresectable stage III NSCLC received 2 cycles of carboplatin at [...]

Mené sur 104 patients atteints d'un cancer rectal de stade localement avancé (âge médian : 57 ans), cet essai de phase II compare, du point de vue notamment du taux de survie sans maladie et du taux de survie globale à 4 ans, l'efficacité d'un protocole thérapeutique comportant une radiothérapie pré-opératoire en combinaison avec une chimiothérapie concomitante par capécitabine-irinotécan ou capécitabine-oxaliplatine, puis une chimiothérapie adjuvante par oxaliplatine-leucovorine-fluorouracile

Efficacy Endpoints of Radiation Therapy Group Protocol 0247: A Randomized, Phase 2 Study of Neoadjuvant Radiation Therapy Plus Concurrent Capecitabine and Irinotecan or Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

Wong, Stuart J. ; Moughan, Jennifer ; Meropol, Neal J. ; Anne, Pramila Rani ; Kachnic, Lisa A. ; Rashid, Asif ; Watson, James C. ; Mitchell, Edith P. ; Pollock, Jondavid ; Lee, R. Jeffrey ; Haddock, Michael ; Erickson, Beth A. ; Willett, Christopher G.

Purpose : To report secondary efficacy endpoints of Radiation Therapy Oncology Group protocol 0247, primary endpoint analysis of which demonstrated that preoperative radiation therapy (RT) with capecitabine plus oxaliplatin achieved a pathologic complete remission prespecified threshold (21%) to merit further study, whereas RT with capecitabine plus irinotecan did not (10%). Methods and Materials : A randomized, phase 2 trial evaluated preoperative RT (50.4 Gy in 1.8-Gy fractions) with 2 [...]

Menée en Allemagne à partir de données portant sur 658 patients atteints d'un cancer rectal entre 1993 et 2010, cette étude montre que l'introduction des traitements multimodaux au cours de la dernière décennie a réduit le taux de récidive locale et amélioré la survie des patients

Multimodal therapy in treatment of rectal cancer is associated with improved survival and reduced local recurrence - a retrospective analysis over two decades

Wiegering, Armin ; Isbert, Christoph ; Dietz, Ulrich ; Kunzmann, Volker ; Ackermann, Sabine ; Kerscher, Alexander ; Maeder, Uwe ; Flentje, Michael ; Schlegel, Nicolas ; Reibetanz, Joachim ; Germer, Christoph-Thomas ; Klein, Ingo

Background : The management of rectal cancer (RC) has substantially changed over the last decades with the implementation of neoadjuvant chemoradiotherapy, adjuvant therapy and improved surgery such as total mesorectal excision (TME). It remains unclear in which way these approaches overall influenced the rate of local recurrence and overall survival. Methods : Clinical, histological and survival data of 658 out of 662 consecutive patients with RC were analyzed for treatment and prognostic [...]

Menée sur 87 patients atteints d'un myélome multiple récidivant ou réfractaire aux traitements, cette étude identifie des critères de substitution à la survie sans progression et à la survie globale pour évaluer, dans les essais cliniques de phase I, l'efficacité de nouveaux agents thérapeutiques

Predictors of survival outcomes in phase 1 relapsed or refractory multiple myeloma patients

Barbee, Meagan S. ; Nooka, Ajay ; Kaufman, Jonathan L. ; Kim, Sungjin ; Chen, Zhengjia ; Heffner, Leonard T. ; Lonial, Sagar ; Harvey, R. Donald

BACKGROUND : The categories of the International Myeloma Working Group (IMWG) response criteria for multiple myeloma are based on the magnitude of the change in paraprotein and the normalization of the free light chain ratio (rFLC). However, the relationship between the response by these biomarkers and clinical outcomes has not been validated with novel compounds in the phase 1 setting. Early response predictors may have prognostic value and speed development plans for new agents. METHODS : The [...]

A partir de données portant sur un total de 16 762 patients atteints d'un cancer colorectal métastatique et ayant été inclus dans un essai clinique d'un traitement de première ligne entre 1997 et 2006, cette étude évalue la corrélation entre le critère de survie sans progression et la survie globale

Individual Patient Data Analysis of Progression-Free Survival Versus Overall Survival As a First-Line End Point for Metastatic Colorectal Cancer in Modern Randomized Trials: Findings From the Analysis and Research in Cancers of the Digestive System Database

Shi, Qian ; de Gramont, Aimery ; Grothey, Axel ; Zalcberg, John ; Chibaudel, Benoist ; Schmoll, Hans-Joachim ; Seymour, Matthew T. ; Adams, Richard ; Saltz, Leonard ; Goldberg, Richard M. ; Punt, Cornelis J.A. ; Douillard, Jean-Yves ; Hoff, Paulo M. ; Hecht, Joel Randolph ; Hurwitz, Herbert ; Díaz-Rubio, Eduardo ; Porschen, Rainer ; Tebbutt, Niall C. ; Fuchs, Charles ; Souglakos, John ; Falcone, Alfredo ; Tournigand, Christophe ; Kabbinavar, Fairooz F. ; Heinemann, Volker ; Van Cutsem, Eric ; Bokemeyer, Carsten ; Buyse, Marc ; Sargent, Daniel J.

Purpose : Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods : Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti–epidermal growth factor receptor [...]