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Port-Saint-Louis-du-Rhône, France

Hadoux J.,Gustave Roussy | Malka D.,Gustave Roussy | Planchard D.,Gustave Roussy | Scoazec J.Y.,Gustave Roussy | And 16 more authors.
Endocrine-Related Cancer | Year: 2015

There is no standard for second-line chemotherapy in poorly differentiated grade 3 neuroendocrine carcinoma (G3-NEC) patients. We analyzed the antitumor efficacy of 5-fluorouracil and oxaliplatin (FOLFOX) chemotherapy in this population. A single-center retrospective analysis of consecutive G3-NEC patients treated with FOLFOX chemotherapy after failure of a cisplatinum-based regimen between December 2003 and June 2012 was performed. Progression-free survival (PFS), overall survival (OS), response rate, and safety were assessed according to RECIST 1.1 and NCI.CTC v4 criteria. Twenty consecutive patients were included (seven males and 13 females; median age 55; range 23-87 years) with a performance status of 0-1 in 75% of them. Primary location was gastroenteropancreatic in 12, thoracic in four, other in two, and unknown in two patients. There were 12 (65%) large-cell and 7 (30%) small-cell G3-NEC tumors, and 1 (5%) unknown. All patients had distant metastases. Twelve (60%) patients received FOLFOX as second-line treatment and 8 (40%) as third-line treatment or later and the median number of administered cycles was 6 (range 3-14). The median follow-up was 19 months. Median PFS was 4.5 months. Among the 17 evaluable patients, five partial responses (29%), six stable diseases (35%), and six progressive diseases (35%) were observed. Median OS was 9.9 months. Main Grade 3-4 toxicities were neutropenia (35%), thrombopenia (20%), nausea/vomiting (10%), anemia (10%), and elevated liver transaminases (10%). Our results indicate that the FOLFOX regimen could be considered as a second-line option in poorly differentiated G3-NEC patients after cisplatinum-based first-line treatment but warrant further confirmation in future larger prospective studies. © 2015 Society for Endocrinology.

Guedj M.,Ligue Nationale Contre le Cancer | Marisa L.,Ligue Nationale Contre le Cancer | De Reynies A.,Ligue Nationale Contre le Cancer | Orsetti B.,Institute Of Recherche En Cancerologie Of Montpellier | And 30 more authors.
Oncogene | Year: 2012

The current histoclinical breast cancer classification is simple but imprecise. Several molecular classifications of breast cancers based on expression profiling have been proposed as alternatives. However, their reliability and clinical utility have been repeatedly questioned, notably because most of them were derived from relatively small initial patient populations. We analyzed the transcriptomes of 537 breast tumors using three unsupervised classification methods. A core subset of 355 tumors was assigned to six clusters by all three methods. These six subgroups overlapped with previously defined molecular classes of breast cancer, but also showed important differences, notably the absence of an ERBB2 subgroup and the division of the large luminal ER+ group into four subgroups, two of them being highly proliferative. Of the six subgroups, four were ER +PR +AR+, one was ER-/PR-/AR-and one was triple negative (AR-/ER-/PR-). ERBB2-amplified tumors were split between the ER-/PR-/AR+ subgroup and the highly proliferative ER+ LumC subgroup. Importantly, each of these six molecular subgroups showed specific copy-number alterations. Gene expression changes were correlated to specific signaling pathways. Each of these six subgroups showed very significant differences in tumor grade, metastatic sites, relapse-free survival or response to chemotherapy. All these findings were validated on large external datasets including more than 3000 tumors. Our data thus indicate that these six molecular subgroups represent well-defined clinico-biological entities of breast cancer. Their identification should facilitate the detection of novel prognostic factors or therapeutical targets in breast cancer. © 2012 Macmillan Publishers Limited All rights reserved.

Sousa P.,Hopital Saint Louis APHP | Allez M.,Hopital Saint Louis APHP
Current Opinion in Gastroenterology | Year: 2015

Purpose of review: The treatment of inflammatory bowel disease (IBD) in the modern area has improved with more biological agents available. Although the efficacy of these drugs has been demonstrated, concerns about their safety profile have been raised, and new data have emerged in the past year. Recent findings: New data regarding the safety profile of anti-TNF were published over the last year, with a better identification of patients at risk of infection, and specific recommendations for the prevention of infections. There is a mild increase in malignancy in patients receiving anti-TNF, mainly lymphoma and skin cancer, which seems mainly attributable to combination with thiopurines. Specific recommendations for management of pregnancy were published. Summary: Biological treatments are effective and safe in the treatment of IBD, provided that the recommendations for their use and monitoring are followed. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Amiot A.,University Paris Est Creteil | Grimaud J.-C.,Aix - Marseille University | Peyrin-Biroulet L.,University of Lorraine | Filippi J.,University of Nice Sophia Antipolis | And 22 more authors.
Clinical Gastroenterology and Hepatology | Year: 2016

Background & Aims: Phase 3 trials have shown the efficacy of vedolizumab, which binds to integrin α4β7, in patients with Crohn's disease (CD) or ulcerative colitis (UC). We investigated the effectiveness and safety of vedolizumab in patients who failed anti-tumor necrosis factor therapy. Methods: From June through December 2014, there were 173 patients with CD and 121 patients with UC who were included in a multicenter nominative compassionate early access program granted by French regulatory agencies. This program provided patients with access to vedolizumab before it was authorized for marketing. Vedolizumab (300 mg) was administered intravenously at weeks 0, 2, and 6, and then every 8 weeks. Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. We report results obtained after the 14-week induction phase. Results: Among the 294 patients treated with vedolizumab (mean age, 39.5 ± 14.0 y; mean disease duration, 10.8 ± 7.6 y; concomitant steroids, 44% of cases), 276 completed the induction period, however, 18 discontinued vedolizumab because of a lack of response (n = 14), infusion-related reaction (n = 2), or infections (n = 2). At week 14, 31% of patients with CD were in steroid-free clinical remission and 51% had a response; among patients with UC, 36% were in steroid-free clinical remission and 50% had a response. No deaths were reported. Severe adverse events occurred in 24 patients (8.2%), including 15 (5.1%) that led to vedolizumab discontinuation (1 case of pulmonary tuberculosis and 1 rectal adenocarcinoma). Conclusions: In a cohort of patients with CD or UC who failed previous anti-tumor necrosis factor therapy, approximately one third of patients achieved steroid-free clinical remission after 14 weeks of induction therapy with vedolizumab. This agent had an acceptable safety profile in these patients. © 2016 AGA Institute.

Gallien S.,Hopital Saint Louis APHP | Gallien S.,University of Paris Pantheon Sorbonne | Gallien S.,French Institute of Health and Medical Research | Flandre P.,French Institute of Health and Medical Research | And 8 more authors.
Journal of Medical Virology | Year: 2015

Due to the differences between bioavailability of efavirenz (EFV) and tenofovir (TDF), the single-tablet regimen of EFV/emtricitabine (FTC)/TDF is not approved as initial antiretroviral therapy (ART) in Europe by the European Medical Agency. To compare clinical, immunological, and virological outcomes between co-formulated TDF/FTC+EFV and the co-formulated EFV/FTC/TDF single-tablet regimen in patients infected with HIV-1 naive to ART, the data of patients (n=231) who initiated either TDF/FTC+EFV (n=155) or EFV/FTC/TDF (n=76) between January 1, 2007 and June 1, 2010 were analyzed. Changes from baseline to week 48 (TDF/FTC+EFV vs. EFV/FTC/TDF) in HIV plasma load (- 3.25 log vs. -3.32 log) and CD4+ T cell count (+180 vs. +138cells/mm3) were similar in the two groups. Treatment discontinuation was recorded in 50 (22%) patients (40 on TDF/FTC+EFV and 10 on EFV/FTC/TDF, P=0.03) but time to discontinuation did not differ between the two groups. Only patients on TDF/FTC+EFV discontinued treatment because of neurological symptoms. Virological failure occurred in 11 (4.7%) patients (seven on TDF/FTC+EFV and four on EFV/FTC/TDF, P=0.75) with new resistance-associated mutations in five among the six with successful resistance genotype tests. Only baseline resistance-associated mutations was a risk factor for virological failure (P=0.0146). These data show comparable outcomes between TDF/FTC+EFV or EFV/FTC/TDF used in patients infected with HIV-1 and not treated previously, consistent with a low rate of virological failure in the absence of pretreatment resistance. This would suggest that the European Medical Agency should approve co-formulated EFV/FTC/TDF single-tablet regimen for patients naive to ART. J. Med. Virol. 87:187-191, 2015.

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