Tartour E.,Hopital Europeen Georges Pompidou |
Tartour E.,University of Paris Descartes |
Zitvogel L.,French Institute of Health and Medical Research |
Zitvogel L.,University Paris - Sud
The Lancet Respiratory Medicine | Year: 2013
Lung cancer is the most common cause of cancer-related mortality worldwide and a therapeutic challenge. Recent success with antibodies blocking immune checkpoints in non-small-cell lung cancers (NSCLC) highlights the potential of immunotherapy for lung cancer treatment, and the need for trials of combination regimens of immunotherapy plus chemotherapy that lead to immunogenic cell death. Here, we review the development of immunogenic cytotoxic compounds, vaccines, and antibodies in NSCLC, in view of their integration into personalised oncology. © 2013 Elsevier Ltd.
Albiges L.,Institute Gustave Roussy |
Chamming's F.,Hopital Europeen Georges Pompidou |
Duclos B.,University of Strasbourg |
Stern M.,Hopital Foch |
And 3 more authors.
Annals of Oncology | Year: 2012
The administration of mammalian target of rapamycin (mTOR) inhibitors can give rise to a potentially life-threatening adverse event, often referred to as 'non-infectious pneumonitis' (NIP), which is characterized by non-infectious, non-malignant, and non-specific inflammatory infiltrates. Patients usually present with cough and/or dyspnoea. We provide a brief description of the mechanism of action of mTOR inhibitors and their overall safety in patients with metastatic renal cell carcinoma (mRCC) and review the literature on mTOR inhibitor-associated NIP in patients with solid tumours. The review was used to derive questions on the diagnosis, management, and monitoring of mRCC patients with NIP, and to develop a decision tree for use in routine clinical practise. A key recommendation was the subdivision of grade 2 NIP into grades 2a and 2b, where grade 2a is closer to grade 1 and grade 2b to grade 3. This subdivision is important because it takes into account the nature and severity of clinical symptoms potentially related to NIP, either the onset of new symptoms or the worsening of existing symptoms, and thus determines the type and frequency of follow-up. It also helps to identify a subgroup of patients in whom treatment, if effective, may be continued without dose adjustment. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Le Heuzey J.-Y.,Hopital Europeen Georges Pompidou |
De Ferrari G.M.,Fondazione IRCCS Policlinico San Matteo |
Radzik D.,Sanofi S.A. |
Santini M.,Ospedale San Filippo Neri |
And 2 more authors.
Journal of Cardiovascular Electrophysiology | Year: 2010
Dronedarone versus Amiodarone in Patients with AF. Introduction: We compared the efficacy and safety of amiodarone and dronedarone in patients with persistent atrial fibrillation (AF). Methods: Five hundred and four amiodarone-naïve patients were randomized to receive dronedarone 400 mg bid (n = 249) or amiodarone 600 mg qd for 28 days then 200 mg qd (n = 255) for at least 6 months. Primary composite endpoint was recurrence of AF (including unsuccessful electrical cardioversion, no spontaneous conversion and no electrical cardioversion) or premature study discontinuation. Main safety endpoint (MSE) was occurrence of thyroid-, hepatic-, pulmonary-, neurologic-, skin-, eye-, or gastrointestinal-specific events, or premature study drug discontinuation following an adverse event. Results: Median treatment duration was 7 months. The primary composite endpoint was 75.1 and 58.8% with dronedarone and amiodarone, respectively, at 12 months (hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.28-1.98; P < 0.0001), mainly driven by AF recurrence with dronedarone compared with amiodarone (63.5 vs 42.0%). AF recurrence after successful cardioversion was 36.5 and 24.3% with dronedarone and amiodarone, respectively. Premature drug discontinuation tended to be less frequent with dronedarone (10.4 vs 13.3%). MSE was 39.3 and 44.5% with dronedarone and amiodarone, respectively, at 12 months (HR = 0.80; 95% CI 0.60-1.07; P = 0.129), and mainly driven by fewer thyroid, neurologic, skin, and ocular events in the dronedarone group. Conclusion: In this short-term study, dronedarone was less effective than amiodarone in decreasing AF recurrence, but had a better safety profile, specifically with regard to thyroid and neurologic events and a lack of interaction with oral anticoagulants. © 2010 Wiley Periodicals, Inc.
Scotte F.,Hopital Europeen Georges Pompidou |
Rey J.B.,Institute Jean Godinot |
Launay-Vacher V.,Service ICAR
Supportive Care in Cancer | Year: 2012
Background Venous thromboembolism (VTE) and renal insufficiency are common in cancer patients. Prompt treatment is necessary to reduce the high rates of VTE-related mortality and morbidity. VTE prophylaxis is underused in cancer patients. We review current recommendations for the treatment and prevention of VTE in cancer patients and discuss low molecular weight heparin (LMWH) use in cases of renal failure. Design This study is a retrospective literature review. Results There are few published recommendations for LMWH use in cancer patients with renal insufficiency. Treatment guidelines largely follow recommendations for other patients with renal failure. Enoxaparin therapy is complicated by the need for regular monitoring of renal function and anti-Xa levels and for dosage adjustment to prevent bleeding. Few data are available to support the systematic use of dalteparin. Tinzaparin is least likely to bioaccumulate in patients with renal failure. Conclusion VTE is the second most common cause of death in cancer patients. Renal insufficiency is present in 50-60 % of cancer patients. Data from renal patients suggest that tinzaparin may be safe and effective for VTE treatment and prevention in cancer patients with renal failure. © Springer-Verlag 2012.
Oudard S.,Hopital Europeen Georges Pompidou |
Beuselinck B.,Hopital Europeen Georges Pompidou |
Decoene J.,Heinrich Heine University Düsseldorf |
Albers P.,Heinrich Heine University Düsseldorf
Cancer Treatment Reviews | Year: 2011
Sunitinib is an orally administered multitargeted tyrosine kinase inhibitor approved multinationally for the first- and second-line treatment of metastatic renal cell carcinoma (mRCC). The recommended dose of sunitinib is 50. mg per day for 4. weeks followed by 2. weeks off-treatment (Schedule 4/2). In a phase III trial in 750 patients with mRCC who had not received prior treatment, sunitinib demonstrated superior efficacy to interferon-α for the first-line treatment of mRCC. Sunitinib doubled progression-free survival compared with interferon-α; furthermore, median OS with sunitinib was greater than 2. years. As a result, sunitinib is now considered a reference standard of care for first-line mRCC treatment in patients at favourable or intermediate prognostic risk and is recommended in treatment guidelines. Additionally, results from an expanded-access programme, in a broad, heterogeneous patient population, confirmed the efficacy of sunitinib. Sunitinib has a distinct and predictable profile of adverse events, most of which are manageable with standard medical interventions. Therapy management strategies, including optimisation of dose and treatment duration and adverse event management can help patients achieve optimal efficacy with sunitinib in clinical practice. To further improve outcomes in patients with mRCC, current trials are evaluating sequencing or combination of targeted agents. The use of sunitinib as adjuvant therapy after nephrectomy and as neoadjuvant therapy is also being assessed. This paper provides an in-depth critical review of sunitinib, with particular focus on the data supporting the use of sunitinib for mRCC. © 2010 Elsevier Ltd.
Chikwe J.,Mount Sinai Medical Center |
Filsoufi F.,Mount Sinai Medical Center |
Carpentier A.F.,Hopital Europeen Georges Pompidou
Nature Reviews Cardiology | Year: 2010
Choosing the optimal aortic valve prosthesis for middle-aged patients (late 40s to early 60s) with aortic stenosis presents a challenge. The available options all have substantial drawbacks that must be considered in the decision-making process. Current data indicate that there is little or no difference in survival between mechanical and bioprosthetic aortic valve replacement in middle-aged patients at 10-15 years after surgery. Patients who receive a mechanical valve replacement have an annual risk of major hemorrhagic or embolic events of 2-4% per year for life compared with about 1% per year for patients who have a bioprosthetic valve. However, bioprostheses are associated with an increasing risk of structural valve degeneration from 10 years postimplantation, and most patients will require reoperation if they survive much longer than a decade. The mortality risk associated with reoperation is similar to that of primary surgery for most patients, and does not seem to impact on the 15-year survival in this patient group. The Ross procedure, in which the aortic valve is replaced with a pulmonary autograft, can provide improved freedom from morbidity, but operative mortality is probably double that of isolated aortic valve replacement and most patients will require reoperation. Informed patient choice is the most important factor in deciding which valve to use, with biological valves increasingly favored over mechanical valves in middle-aged patients. © 2010 Macmillan Publishers Limited. All rights reserved.
I-ADD Study: Assessment of Efficacy and Safety Profile of Irbesartan/Amlodipine Fixed-Dose Combination Therapy Compared With Irbesartan Monotherapy in Hypertensive Patients Uncontrolled With Irbesartan 150 mg Monotherapy: A Multicenter, Phase III, Prospective, Randomized, Open-Label With Blinded-End Point Evaluation Study
Bobrie G.,Hopital Europeen Georges Pompidou
Clinical Therapeutics | Year: 2012
Background: Hypertension guidelines recommend the use of 2 agents with synergistic action when >1 agent is needed to achieve blood pressure goals. Newer antihypertensive treatment combinations include fixed-dose combinations of an angiotensin receptor blocker and a calcium channel blocker. Objective: The I-ADD study aimed to demonstrate whether the antihypertensive efficacy of fixed-dose combination irbesartan 300 mg/amlodipine 5 mg (I300/A5) was superior to that of irbesartan (I300) monotherapy in lowering home systolic blood pressure after 10 weeks' treatment. Methods: The I-ADD study was a 10-week, multicenter, Phase III, prospective, randomized, parallel-group, open-label with blinded-end point study. The main inclusion criterion was essential uncontrolled hypertension (systolic blood pressure ≥145 mm Hg at office after at least 4 weeks of irbesartan 150 mg [I150] monotherapy administered once daily). Patients continued to receive I150 for 7 to 10 days and were randomized to either monotherapy with I150 for 5 weeks then I300 for the next 5 weeks, or to a fixed-dose combination therapy (I150/A5, then I300/A5). Safety profile was assessed by recording adverse events reported by patients or observed by the investigator. Results: Following enrollment, 325 patients were randomized to treatment, and 320 (mean [SD] age, 56.7 [11.4] years; 41% male) were included in the intention-to-treat analysis: 155 patients treated with I150/A5 then I300/A5, and 165 patients treated with I150 then I300. At randomization, mean home systolic blood pressure was similar in both groups: 152.7 (11.8) mm Hg in the I150/A5 group and 150.4 (10.1) mm Hg in the I150 group. At week 10, the adjusted mean difference in home systolic blood pressure between groups was -8.8 (1.1) mm Hg (P < 0.001). The percentage of controlled patients (mean home blood pressure <135 and 85 mm Hg) was nearly 2-fold higher in the I300/A5 group versus the I300 group (P < 0.001). Treatment-emergent adverse events were experienced by 10.5% of I300/A5-treated patients and 6.6% of I300-treated patients during the second 5-week period. Three serious adverse events were reported; 2 with monotherapy (1 with I150 and 1 with I300) and 1 with fixed-dose combination I300/A5. All patients affected by serious adverse events made a full recovery. Conclusions: These 10-week data from this patient population suggest a greater antihypertensive efficacy of the fixed-dose combination I300/A5 over I300 alone in lowering systolic blood pressure. Both treatments were well tolerated throughout the study. ClinicalTrials.gov identifier: NCT00957554. © 2012 Elsevier HS Journals, Inc.
I-COMBINE Study: Assessment of Efficacy and Safety Profile of Irbesartan/Amlodipine Fixed-Dose Combination Therapy Compared With Amlodipine Monotherapy in Hypertensive Patients Uncontrolled With Amlodipine 5 mg Monotherapy: A Multicenter, Phase III, Prospective, Randomized, Open-Label With Blinded-End Point Evaluation Study
Bobrie G.,Hopital Europeen Georges Pompidou
Clinical Therapeutics | Year: 2012
Background: Hypertension guidelines recommend the use of 2 agents with synergistic action when >1 agent is needed to achieve blood pressure goals. Newer antihypertensive treatment combinations include fixed-dose combinations of an angiotensin receptor blocker and a calcium channel blocker. Objective: The I-COMBINE study aimed to determine whether the antihypertensive efficacy of the fixed-dose combination irbesartan 150 mg/amlodipine 5 mg (I150/A5) was superior to that of amlodipine 5 mg (A5) monotherapy in lowering home systolic blood pressure (HSBP) after 5 weeks' treatment. Methods: The I-COMBINE study was a 10-week, multicenter, Phase III, prospective, randomized, parallel-group, open-label with blinded-endpoint study. The main inclusion criterion was essential uncontrolled hypertension (SBP ≥145 mm Hg at office, after at least 4 weeks of A5 monotherapy administered once daily). Patients continued to receive A5 for 7 to 10 days and were randomized to either monotherapy with A5 for 5 weeks then amlodipine 10 mg (A10) for the next 5 weeks or to a fixed-dose combination therapy (I150/A5 then I150/A10). Safety profile was assessed by recording adverse events reported by patients or observed by the investigator. Results: Following enrollment, 290 patients were randomized to treatment, and 287 (mean [SD] age, 57.3 [11.2] years; 48% male) were included in the intention-to-treat analysis: 144 patients treated with I150/A5 then I150/A10, and 143 patients treated with A5 then A10. At randomization, mean HSBP was similar in both groups: 148.5 (10.3) mm Hg in the I150/A5 group and 149.2 (9.7) mm Hg in the A5 group. At week 5, the adjusted mean difference in HSBP between groups was -6.2 (1.0) mm Hg (P < 0.001). The proportion of controlled patients (mean home blood pressure <135 and 85 mm Hg) was significantly higher in the I150/A5 group than in the A5 group (P < 0.001). Treatment-emergent adverse events were experienced by 13.8% of I150/A5-treated patients and 11.9% of A5-treated patients during the first 5-week period, and by 15.8% of I150/A10-treated patients and 17.0% of A10-treated patients during the second 5-week period. Two serious adverse events were reported with the fixed-dose combination; both patients recovered. Conclusions: Data from this adult population with essential hypertension suggest greater efficacy with the fixed-dose combination I150/A5 over A5 monotherapy in lowering SBP after 5 weeks. Both treatment regimens were well tolerated throughout the study. ClinicalTrials.gov identifier: NCT00956644. © 2012 Elsevier HS Journals, Inc.
Housset M.,Hopital Europeen Georges Pompidou
Bulletin du cancer | Year: 2010
Bladder cancer is the second most common urologic tumor after prostate cancer. Radical cystectomy is the standard treatment of localized muscle-invasive tumors. However, urinary diversion (using a conduit or continent diversion) following radical cystectomy can be debilitating. Moreover, delayed metastases appear frequently in spite of radical surgery. So, for selected patients, chemoradiotherapy is a valid therapeutic alternative to cystectomy. Cisplatin or derivatives are administered concurrently to radiation therapy up to 60-65 Gy. Patients undergo control cystoscopy at mid-course in treatment in order to select responders from non responders. This review summarizes the main published series of radiochemotherapy in invasive bladder cancer. Results for local control, survivals, bladder preservation rates and toxicity are presented.
Vargas-Poussou R.,Hopital Europeen Georges Pompidou
Clinical Journal of the American Society of Nephrology | Year: 2012
Background and objectives Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a rare autosomal recessive renal tubular disease. It is caused by mutations in CLDN16 and CLDN19, encoding claudin- 16 and -19, respectively. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is usually complicated by progressive CKD. The objectives of this study were to describe the clinical and genetic features of familial hypomagnesemia with hypercalciuria and nephrocalcinosis and analyze phenotype-genotype associations in patients with CLDN16 or CLDN19 mutations. Design, setting, participants, & measurements Data from 32 genetically confirmed patients (9 patients with CLDN16 and 23 patients with CLDN19 mutations) from 26 unrelated families were retrospectively reviewed. Results Diagnosis was based on clinical criteria at a median age of 9.5 years and confirmed by genetic testing at a median age of 15.5 years. In total, 13 CLDN16 or CLDN19mutationswere identified, including 8 novel mutations. A founder effect was detected for the recurrent CLDN16 p.Ala139Valmutation in North African families and the CLDN19 p.Gly20Asp mutation in Spanish and French families. CKD was more frequently observed in patients with CLDN19 mutations: survival without CKD or ESRD was 56% at 20 years of age in CLDN19 versus 100% in CLDN16 mutations (log rank P,0.01). Ocular abnormalities were observed in 91% of patients with CLDN19 mutations and none of the patients with CLDN16 mutations (P,0.01). Treatments seem to have no effect on hypercalciuria and CKD progression. Conclusions Patients with CLDN19 mutations may display more severe renal impairment than patients with CLDN16 mutations. Ocular abnormalities were observed only in patients with CLDN19 mutations. © 2012 by the American Society of Nephrology.