Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): An intergroup, open-label, randomised phase 3 trial
Sternberg C.N.,San Camillo and Forlanini Hospitals |
Skoneczna I.,Maria Sklodowska Curie Memorial Cancer Center |
Kerst J.M.,Netherlands Cancer Institute |
Albers P.,Klinikum Kassel |
And 28 more authors.
The Lancet Oncology | Year: 2015
Background: Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder. Methods: This intergroup, open-label, randomised, phase 3 trial recruited patients from hospitals across Europe and Canada. Eligible patients had histologically proven urothelial carcinoma of the bladder, pT3-pT4 disease or node positive (pN1-3) M0 disease after radical cystectomy and bilateral lymphadenectomy, with no evidence of any microscopic residual disease. Within 90 days of cystectomy, patients were centrally randomly assigned (1:1) by minimisation to either immediate adjuvant chemotherapy (four cycles of gemcitabine plus cisplatin, high-dose methotrexate, vinblastine, doxorubicin, and cisplatin [high-dose MVAC], or MVAC) or six cycles of deferred chemotherapy at relapse, with stratification for institution, pT category, and lymph node status according to the number of nodes dissected. Neither patients nor investigators were masked. Overall survival was the primary endpoint; all analyses were by intention to treat. The trial was closed after recruitment of 284 of the planned 660 patients. This trial is registered with ClinicalTrials.gov, number NCT00028756. Findings: From April 29, 2002, to Aug 14, 2008, 284 patients were randomly assigned (141 to immediate treatment and 143 to deferred treatment), and followed up until the data cutoff of Aug 21, 2013. After a median follow-up of 7·0 years (IQR 5·2-8·7), 66 (47%) of 141 patients in the immediate treatment group had died compared with 82 (57%) of 143 in the deferred treatment group. No significant improvement in overall survival was noted with immediate treatment when compared with deferred treatment (adjusted HR 0·78, 95% CI 0·56-1·08; p=0·13). Immediate treatment significantly prolonged progression-free survival compared with deferred treatment (HR 0·54, 95% CI 0·4-0·73, p<0·0001), with 5-year progression-free survival of 47·6% (95% CI 38·8-55·9) in the immediate treatment group and 31·8% (24·2-39·6) in the deferred treatment group. Grade 3-4 myelosuppression was reported in 33 (26%) of 128 patients who received treatment in the immediate chemotherapy group versus 24 (35%) of 68 patients who received treatment in the deferred chemotherapy group, neutropenia occurred in 49 (38%) versus 36 (53%) patients, respectively, and thrombocytopenia in 36 (28%) versus 26 (38%). Two patients died due to toxicity, one in each group. Interpretation: Our data did not show a significant improvement in overall survival with immediate versus deferred chemotherapy after radical cystectomy and bilateral lymphadenectomy for patients with muscle-invasive urothelial carcinoma. However, the trial is limited in power, and it is possible that some subgroups of patients might still benefit from immediate chemotherapy. An updated individual patient data meta-analysis and biomarker research are needed to further elucidate the potential for survival benefit in subgroups of patients. © 2015 Elsevier Ltd.
PubMed | Center dEtudes du Polymorphisme Humain, Center Paul Strauss, Center Doncologie Et Of Radiotherapie Du Parc, Center Leon Berard and 24 more.
Type: Journal Article | Journal: Oncotarget | Year: 2016
Genetic polymorphisms are associated with breast cancer risk. Clinical and epidemiological observations suggest that clinical characteristics of breast cancer, such as estrogen receptor or HER2 status, are also influenced by hereditary factors. To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098). Strong association between the FGFR2 locus and ER status of breast cancer patients was observed (ER-positive n=6211, ER-negative n=2516; rs3135718 OR=1.34 p=5.4610-12). This association was limited to patients with HER2-negative tumors (ER-positive n=4267, ER-negative n=1185; rs3135724 OR=1.85 p=1.1610-11). The FGFR2 locus is known to be associated with breast cancer risk. This study provides sound evidence for an association between variants in the FGFR2 locus and ER status among breast cancer patients, particularly among patients with HER2-negative disease. This refinement of the association between FGFR2 variants and ER-status to HER2-negative disease provides novel insight to potential biological and clinical influence of genetic polymorphisms on breast tumors.
Pazopanib plus best supportive care versus best supportive care alone in advanced gastrointestinal stromal tumours resistant to imatinib and sunitinib (PAZOGIST): a randomised, multicentre, open-label phase 2 trial
PubMed | Direction of Clinical Research and Innovation, Institute Paoli Calmettes, Institute Bergonie, Institute Of Cancerologie Of Lorraine Alexis Vautrin and 8 more.
Type: Journal Article | Journal: The Lancet. Oncology | Year: 2016
Gastrointestinal stromal tumours (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract. Imatinib followed by sunitinib and regorafenib is the standard sequence of treatment for advanced disease. Pazopanib is effective in soft tissue sarcomas but has never been assessed in advanced GIST in a randomised trial. We aimed to assess the efficacy and safety of pazopanib in patients with previously treated advanced GIST.In this randomised, open-label phase 2 study, we enrolled adults (aged 18 years) with advanced GIST resistant to imatinib and sunitinib from 12 comprehensive cancer centres or university hospitals in France and randomly assigned them 1:1 using an interactive web-based centralised platform to 800 mg oral pazopanib once daily in 4-week cycles plus best supportive care or best supportive care alone. Randomisation was stratified by the number of previous treatment regimens (2 vs 3); no-one was masked to treatment group allocation. Upon disease progression, patients in the best supportive care group were allowed to switch to pazopanib as compassionate treatment. The primary endpoint was investigator-assessed progression-free survival, analysed by intention-to-treat. All randomised participants who received at least one dose of pazopanib were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01323400.Between April 12, 2011, and Dec 9, 2013, 81 patients were enrolled and randomly assigned to pazopanib plus best supportive care (n=40) or best supportive care alone (n=41). The median follow-up was 264 months (IQR 220-378) in the pazopanib plus best supportive care group and 289 months (220-352) in the best supportive care group. 4-month investigator-assessed progression-free survival was 452% (95% CI 291-600) in the pazopanib plus best supportive care group versus 176% (78-308) in the best supportive care group (hazard ratio [HR] 059, 95% CI 037-096; p=0029). Median progression-free survival was 34 months (95% CI 24-56) with pazopanib plus best supportive care and 23 months (21-33) with best supportive care alone (HR 059 [037-096], p=003). 36 (88%) of the patients originally assigned to the best supportive care group switched to pazopanib following investigator-assessed disease progression; these patients had a median progression-free survival from pazopanib initiation of 35 months (95% CI 22-52). 55 (72%) of the 76 pazopanib-treated patients had pazopanib-related grade 3 or worse adverse events, the most common of which was hypertension (15 [38%] in the pazopanib plus best supportive care group and 13 [36%] in the best supportive care group). 20 (26%) patients had pazopanib-related serious adverse events (14 [35%] in the pazopanib plus best supportive care group and six [17%] in the best supportive care group), including pulmonary embolism in eight (9%) patients (five [13%] in the pazopanib plus best supportive care group and three [7%] in the best supportive care group). Three pazopanib-related deaths occurred (two pulmonary embolisms [one in each group] and one hepatic cytolysis [in the best supportive care group]). Three adverse event-related but not pazopanib-related deaths occurred in the best supportive care group after switch to pazopanib; these deaths were from hyperammonaemic encephalopathy, pneumopathy, and respiratory failure.Pazopanib plus best supportive care improves progression-free survival compared with best supportive care alone in patients with advanced GIST resistant to imatinib and sunitinib, with a toxicity profile similar to that reported for other sarcomas. This trial provides reference outcome data for future studies of targeted inhibitors in the third-line setting for these patients.GlaxoSmithKline, French National Cancer Institute, EuroSARC (FP7-278742), Centre Lon Brard.
PubMed | Institute Of Cancerologie Of Lorraine Alexis Vautrin, University Claude Bernard Lyon 1 and Institute Of Cancerologie Of Louest
Type: | Journal: Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique | Year: 2016
Recent technological developments led to develop the concept of focused liver radiation therapy. We must distinguish primary and secondary tumors as the indications are restricted and must be discussed as an alternative to surgical or medical treatments. For hepatocellular carcinoma 5to 10cm (or more), a conformational radiation with or without intensity modulation is performed. Stereotactic body radiotherapy (SBRT) is being evaluated and is increasingly proposed as an alternative to radiofrequency ablative treatment for primary or secondary tumors (typically less than 5cm). Tumor (and liver) movements induced by respiratory motions must be taken into account. Strict dosimetric criteria must be met with particular attention to the dose-volume histograms to liver and the hollow organs, including cases of SBRT.
PubMed | Institute Of Cancerologie Of Lorraine Alexis Vautrin, University of Bordeaux 1, University Claude Bernard Lyon 1, Institute Bergonie and 10 more.
Type: | Journal: European journal of cancer (Oxford, England : 1990) | Year: 2016
Imatinib has dramatically improved the prognosis of advanced gastrointestinal stromal tumours (GISTs). Clinical trial data showed that patients with trough imatinib plasma concentrations (Cmin) below 1100 ng/ml (quartile 1) had shorter time to progression, but no threshold has been defined. The main objective of this study was to investigate in advanced GIST whether a Cmin threshold value associated with a longer progression-free survival (PFS) could be specified. This would be the first step leading to therapeutic drug monitoring of imatinib in GIST.Advanced GIST patients (n=96) treated with imatinib 400 mg/d (41 stomach, 34 small bowel, and 21 other primary site localisations) were prospectively included in this real-life setting study. Routine plasma level testing imatinib (Cmin) and clinical data of were recorded prospectively.Small bowel localisation was associated with an increased relative risk of progression of 3.09 versus stomach localisation (p=0.0255). Mean Cmin (standard deviation) was 868 (536) ng/ml with 75% inter-individual and 26% intra-patient variability. A Cmin threshold of 760 ng/ml defined by log-rank test was associated with longer PFS for the whole population (p=0.0256) and for both stomach (p=0.043) and small bowel (p=0.049) localisations when analysed separately. Multivariate Cox regression analysis found that Cmin above 760 ng/ml was associated with 65% reduction risk of progression (p=0.0271) in the whole population independently of the anatomical localisation.Concentration of imatinib significantly influences duration of tumour control treatment in GIST patients with a Cmin threshold of 760 ng/ml associated with prolonged PFS in real-life setting.
PubMed | Institute Of Cancerologie Of Lorraine Alexis Vautrin, Center Georges Francois Leclerc, Center Leon Berard, Center Regional Of Lutte Contre Le Cancer Eugene Marquis and 2 more.
Type: | Journal: Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique | Year: 2016
Prostate brachytherapy techniques are described, concerning both Iodine125high dose rate brachytherapy. The following parts are presented: brachytherapy indications, technical description, immediate postoperative management and post-treatment evaluation, and 4to 6weeks as well as long-term follow-up.
PubMed | Institute Of Cancerologie Of Lorraine Alexis Vautrin, Hopitaux Universitaires Of Strasbourg, University of Bordeaux 1, Laboratoire Hospira France and Lyon Sud Hospital
Type: | Journal: OncoTargets and therapy | Year: 2016
Chemotherapy-induced anemia (CIA) is a frequent complication among cancer patients, with elderly patients more likely to suffer severe effects. Biosimilar erythropoiesis-stimulating agents lower costs of supportive cancer treatment, and thus are particularly relevant in the elderly cancer population, which is growing rapidly worldwide. The goal of this subanalysis was to compare the tolerability and effectiveness of an epoetin biosimilar for treating CIA in patients <70 years old vs patients 70 years old.The ORHEO observational trial enrolled patients with CIA (hemoglobin [Hb] <11 g/dL) in association with chemotherapy for solid tumors, lymphoma, or myeloma. Patients received an epoetin biosimilar and were evaluated at 3 and 6 months for response, defined as achieving target Hb without blood transfusions during the 3 weeks preceding measurement, Hb 10 g/dL, or Hb increase 1 g/dL since study enrollment. Secondary end points included changes in Hb level, treatment interruptions, transfusion rates, and adverse events.Among the 2,310 original patients, 1,301 <70 years old were compared to 1,009 70 years old. Almost all patients (99.9%) received the biosimilar epoetin zeta (Retacrit). Patients in both groups responded well to treatment with biosimilar epoetin, with 79.8% and 84% responding at 3 months and 86.3% and 86.8% at 6 months among younger and elderly cohorts, respectively. Biosimilar epoetin therapy was well tolerated, with adverse events reported in only 17.6% and 16.4% of younger and elderly patients, respectively. A greater number of thromboembolic events and a lesser rate of infections were reported in the elderly, but were still lower than reported in clinical registration trials. No treatment fatalities occurred in either group.Biosimilar epoetin was an effective and well-tolerated treatment for managing CIA in elderly cancer patients.
PubMed | Institute Of Cancerologie Of Lorraine Alexis Vautrin, Center Oscar Lambret, The Surgical Center and Institute Claudius Regaud
Type: Journal Article | Journal: Journal of surgical oncology | Year: 2016
The French Sentimag feasibility trial evaluated a new method for the localization of breast cancer sentinel lymph node (SLN) using Sienna+, superparamagnetic iron oxide particles, and Sentimag detection in comparison to the standard technique (isotopes blue dye).We conducted a prospective multicentric paired comparison trial on 115 patients. SLN localization was performed using both the magnetic technique and the standard method. Detection rate and concordance between magnetic and standard tracers were calculated. Post-operative complications were assessed after 30 days.Results are based on 108 patients. SLN identification rate was 98.1% [93.5-99.8] for both methods, 97.2% [92.1-99.4] for Sienna+ and 95.4% [89.5-98.5] for standard technique. A mean of 2.1 SLNs per patient was removed. The concordance rate was 99.0% [94.7-100.0%] per patient and 97.4% [94.1-99.2] per node. Forty-six patients (43.4%) had nodal involvement. Among involved SLNs, concordance rate was 97.7% [88.0-99.9] per patient and 98.1% [90.1-100.0] per node.This new magnetic tracer is a feasible method and a promising alternative to the isotope. It could offer benefits for ambulatory surgery or sites without nuclear medicine departments. J. Surg. Oncol. 2016;113:501-507. 2016 Wiley Periodicals, Inc.
Peiffert D.,The Saints |
Peiffert D.,Institute Of Cancerologie Of Lorraine Alexis Vautrin |
Hannoun-Levi J.-M.,Center Antoine Lacassagne
Cancer/Radiotherapie | Year: 2013
During the last decade, the organization of brachytherapy in France moved to 62 units in 173 radiotherapy centres in 2009. More than 7500 patients were treated in 2009, quite exclusively with curative intent, for 80% in public or associated hospitals. The techniques improved to high tech 3D dosimetry and optimization of the dose distribution. Brachytherapy, despite representing only 5% of the treatments by irradiation, is a reference treatment for several tumors. © 2013.