Center Gf Leclerc

Dijon, France

Center Gf Leclerc

Dijon, France
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Bottomley A.,European Organization for Research and Treatment of Cancer | Bottomley A.,University of Verona | Tridello G.,European Organization for Research and Treatment of Cancer | Coens C.,European Organization for Research and Treatment of Cancer | And 10 more authors.
Cancer | Year: 2014

Background The European Organization for Research and Treatment of Cancer (EORTC) 24954 phase 3 randomized clinical trial compared 2 schemes of combined chemotherapy for patients with resectable cancers of the hypopharynx and larynx: sequential induction chemotherapy and radiotherapy versus alternating chemoradiotherapy. The current study reports detailed effects of both treatment arms on health-related quality of life (HRQOL) and symptoms. Methods A total of 450 patients aged 35 years to 76 years (World Health Organization performance status (WHO PS) ≤ 2) with untreated, resectable advanced squamous cell carcinoma of the larynx (tumor classification of T3-T4) or hypopharynx (tumor classification of T2-T3-T4) with regional lymph nodes in the neck classified as N0 to N2 with no metastases were randomized in this prospective phase 3 trial into either the sequential arm (control) or the alternating arm (experimental). QOL assessment was performed at randomization; at baseline; at 42 days; and at 6, 12, 24, 36, and 48 months. Results There were no observed differences with regard to the primary endpoint of Fatigue and secondary endpoint of Dyspnea. Significant differences were found in the secondary endpoints of Swallowing and Speech problems at 42 days after randomization in favor of patients in the sequential arm. Explanatory and sensitivity analysis revealed that the primary analysis favored the sequential arm, but the majority of differences in HRQOL did not exist at the end of treatment, and returned to baseline levels. Conclusions In the current study, a trend toward worse scores was noted in the patients treated on the alternating chemoradiotherapy arm but very few differences reached the level of statistical significance. The HRQOL scores of the majority of patients returned to baseline after therapy. © 2013 American Cancer Society.


Flechon A.,Center Leon Berard | Pouessel D.,Center Val dAurelle | Ferlay C.,Center Leon Berard | Perol D.,Center Leon Berard | And 9 more authors.
Annals of Oncology | Year: 2011

Background: In the evolution of metastatic castration-resistant prostate cancer (mCRPC), patients present visceral metastases with or without neuroendocrine differentiation in 20% of cases. Patients and methods: We assessed the efficacy and toxicity of a platinum-based chemotherapy regimen in mCRPC patients with either neuroendocrine differentiation defined by high serum levels of chromogranin A (CgA) and neuron-specific enolase (NSE) or visceral metastases. Patients received the combination of carboplatin and etoposide every 3 weeks. Efficacy end points included prostate-specific antigen (PSA) and neuroendocrine marker response, objective response and toxicity. Results: Of the 60 patients included from April 2005 to January 2008, 78.6% had bone metastases, 46.4% had lymph node involvement and 57.1% had liver and/or lung localizations. The objective response rate was 8.9% in the 46 patients with measurable disease. A neuroendocrine response was observed in 31% of cases for NSE and 7% for CgA. The PSA response rate was 8%. The most common grade 3-4 treatment-related toxic effects were neutropenia (65.5%), thrombocytopenia (32.7%) and anemia (27.3%). There was 7.2% febrile neutropenia, with one toxicity-related death. The median follow-up was 9.3 months [95% confidence interval (CI) 0.2-27.1] and the median overall survival 9.6 months (95% CI 8.7-12.7). Conclusion: The benefit-risk ratio of this regimen seems unfavorable due to poor response and high toxicity. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Groheux D.,Paris West University Nanterre La Défense | Groheux D.,University Paris Diderot | Mankoff D.,University of Pennsylvania | Lemarignier C.,Paris West University Nanterre La Défense | And 8 more authors.
Medecine Nucleaire | Year: 2016

Over the past few years, several studies have focused attention on the impact of breast cancer (BC) histological subtype or BC phenotype, as defined by hormone receptors (HR) and HER2 status, on the results of FDG-PET/CT at staging, or during neoadjuvant chemotherapy (NAC). At staging, sclerotic bone metastases from invasive lobular carcinoma (ILC) demonstrated low or no FDG uptake in comparison to metastases from invasive ductal carcinoma (IDC). The CT component of PET/CT imaging should be carefully analyzed in the staging of ILC. In patients with triple negative or HER2-positive tumors, the proportion of extraskeletal metastases is high; this must be taken into account in the diagnostic strategy. Staging based on PET/CT findings offers higher prognostic stratification value than that defined by conventional imaging workup. The yield and prognostic information are high in patients with clinical stage IIB or higher. Moreover, the intensity of tumor FDG uptake at baseline may have prognostic value for recurrence, with stronger evidence in HR-positive/HER2-negative phenotype. In the assessment of tumor response to NAC, the metabolic response, generally based on the change in SUVmax (δSUVmax), depends on the BC subtypes. In triple negative BC, a good metabolic response early during NAC has been shown to be predictive of pCR, and the predictive value was reinforced by combining δSUVmax and EGFR status. In 171 patients, no correlation was found between some recently developed PET-derived parameters, i.e. tumor heterogeneity or textural analysis, and BC subtypes. Whether these parameters offer any advantage compared to SUV measurements remains to be demonstrated. © 2015 Elsevier Masson SAS.


Humbert O.,Center Gf Leclerc | Humbert O.,Center Hospitalo University Le Bocage | Humbert O.,University of Burgundy | Cochet A.,Center Gf Leclerc | And 8 more authors.
Oncologist | Year: 2015

This review considers the potential utility of positron emission tomography (PET) tracers in the setting of response monitoring in breast cancer, with a special emphasis on glucose metabolic changes assessed with 18F-fluorodeoxyglucose (FDG). In the neoadjuvant setting of breast cancer, the metabolic response can predict the final complete pathologic response after the first cycles of chemotherapy. Because tumor metabolic behavior highly depends on cancer subtype, studies are ongoing to define the optimal metabolic criteria of tumor response in each subtype.The recent multicentric randomized AVATAXHER trial has suggested, in the human epidermal growth factor 2-positive subtype, a clinical benefit of early tailoring the neoadjuvant treatment in women with poor metabolic response after the first course of treatment. In the bone-dominant metastatic setting, there is increasing clinical evidence that FDG-PET/computed tomography (CT) is the most accurate imaging modality for assessment of the tumor response to treatment when both metabolic information and morphologic information are considered. Nevertheless, there is a need to define standardized metabolic criteria of response, including the heterogeneity of response among metastases, and to evaluate the costs and health outcome of FDG-PET/CT compared with conventional imaging. New non-FDG radiotracers highlighting specific molecular hallmarks of breast cancer cells have recently emerged in preclinical and clinical studies. These biomarkers can take into account the heterogeneity of tumor biology in metastatic lesions. They may provide valuable clinical information for physicians to select and monitor the effectiveness of novel therapeutics targeting the same molecular pathways of breast tumor. © AlphaMed Press 2015.


Kanoun S.,Center Gf Leclerc | Rossi C.,Hematologie Clinique | Berriolo-Riedinger A.,Center Gf Leclerc | Dygai-Cochet I.,Center Gf Leclerc | And 7 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2014

Purpose: The presence of a bulky tumour at staging in Hodgkin lymphoma (HL) is a predictor of a poor outcome. The total metabolic tumour volume at baseline (TMTV0) computed on PET may improve the evaluation of tumour burden. To explore the clinical usefulness of TMTV0, we compared the prognostic value of TMTV0, tumour bulk and interim PET response in a retrospective single-centre study. Methods: From 2007 to 2010, 59 consecutive patients with a first diagnosis of HL were treated in our institution. PET was done at baseline (PET0) and after two cycles of chemotherapy (PET2), and treatment was not modified according to the PET2 result. TMTV0 was measured with a semiautomatic method using a 41 % SUVmax threshold. SUVmax reduction between PET0 and PET2 (ΔSUVmaxPET0-2) was also computed. Based on ROC analysis, patients with a ΔSUVmaxPET0-2 >71 % were considered good responders and a TMTV0 >225 ml was considered to represent hypermetabolic bulky disease. Results: Median TMTV0 was 117 ml and 17 patients (29 %) had a TMTV0 >225 ml. TMTV0 (>225 ml vs. ≤225 ml) and tumour bulk (<10 cm vs. ≥10 cm) were predictive of 4-year PFS: 42 % vs. 85 % (p=0.001) and 44 % vs. 79 % (p < 0.03), respectively. In multivariate analysis, using ΔSUVmaxPET0-2, TMTV0 and bulky tumour as covariates, only ΔSUVmaxPET0-2 (p=0.0005, RR 6.3) and TMTV0 (p < 0.006, RR 4.4) remained independent predictors of PFS. Three prognosis groups were thus identified: ΔSUVmaxPET0-2 >71 % and TMTV0 ≤225 ml (n=37, 63 %), ΔSUVmaxPET0-2=<71 % or TMTV0 >225 ml (n=17, 29 %), and ΔSUVmaxPET0-2=<71 % and TMTV0 >225 ml (n=5, 8 %). In these three groups the 4-year PFS rates were 92 %, 49 %, and 20 % (p < 0.0001), respectively. Conclusion: TMTV0 is more relevant than tumour bulk for predicting the outcome in patients with HL, and adds a significant prognostic insight to interim PET response assessment. The combination of TMTV0 and ΔSUVmaxPET0-2 made it possible to identify three subsets of HL patients with different outcomes. This may guide clinicians in their choice of therapeutic strategy. © 2014 Springer-Verlag.


Tourani J.M.,University of Poitiers | Mourey L.,Institute Claudius Regaud | Servent V.,Center Oscar Lambret | Nguyen T.,Besancon University Hospital Center | And 5 more authors.
Journal of Geriatric Oncology | Year: 2012

Objective: Vinflunine (VFL) is a novel microtubule inhibitor indicated in the treatment of advanced or metastatic urothelial transitional cell cancer after failure of a prior platinum-containing regimen at the recommended dose of 320. mg/m 2 q3 weeks. This trial was designed to assess the pharmacokinetic (PK) behavior and tolerance of VFL in elderly patients (pts), and to propose dose-adjustments if necessary. Material and methods: Three groups of cancer pts over 70. years old (y) were open to recruitment: 70-75. y, 75-80. y and ≥ 80 y. Each group of pts received intravenous VFL, respectively at 320, 280 and 250. mg/m 2 on cycle 1. Pharmacokinetics and safety data were collected at cycle 1 and were compared to reference values from younger pts < 70. y. Results: 46 pts were treated. For pts 70-75y and 75-80y, there was no statistically age-related change for VFL PK. For pts ≥80y, VFL blood total clearance (Cl tot) was significantly decreased by 18%. The most common adverse events observed in this elderly population were not different from those seen in younger pts. No toxic death was recorded. Main toxicities were neutropenia (Grade 3/4: 73% of pts), constipation (all grade: 63%) and asthenia (all grade: 56%), without any relationship between the observed incidence and the ageing of pts. Conclusion: Based on PK and safety data, a dose reduction at 280. mg/m 2 and 250. mg/m 2 is recommended in pts 75-80. y and ≥ 80. y respectively. © 2011 Elsevier Inc.


Humbert O.,Center Gf Leclerc | Berriolo-Riedinger A.,Center Gf Leclerc | Riedinger J.M.,Center Gf Leclerc | Coudert B.,Center Gf Leclerc | And 8 more authors.
Annals of Oncology | Year: 2012

Background: The aim of this study is to evaluate the impact of the different breast cancer subtypes on the tumor. 18F-FDG uptake at baseline and on its changes after the first course of neoadjuvant chemotherapy (NAC). Patients and Methods: One hundred and fifteen women with newly diagnosed, large or locally advanced breast cancer undergoing NAC were included. Estrogen receptor (ER), progesterone receptor (PR) and HER2 status were used to define three major tumor subtypes: triple negative (TN) (ER-/PR-/HER2-), luminal (ER+ and/or PR+; HER2-) and HER2 positive (HER2+). Using Fluorine-18 fluorodeoxyglucose positron emission tomography, the tumoral standard uptake value (SUV) maximal index was measured at baseline and just before the second course of NAC. Results: TN tumors presented the highest baseline SUV (11.3 ± 8.5; P < 0.0001). The decrease of SUV after the first course of NAC (ΔSUV) was significantly higher in TN and HER2-positive subtypes (-45% ± 25% and -57% ± 30%, respectively) than in luminal one (-19% ± 35%; P < 0.0001). ΔSUV was a predictive factor of the pathological complete response only in HER2-positive tumors (cut-off = -75%; P < 0.03) with an accuracy of 76%. Conclusion: The baseline. 18F-FDG tumoral uptake but also its early response to NAC is different according to the immunohistological subtypes of breast cancer. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Isambert N.,Center Gf Leclerc | Delord J.P.,Institute Claudius Regaud | Tourani J.M.,Chu de Poitiers | Fumoleau P.,Center Gf Leclerc | And 5 more authors.
British Journal of Clinical Pharmacology | Year: 2014

Aims Vinflunine (VFL) ditartrate, a novel tubulin-targeted inhibitor, is registered for the treatment of patients with advanced or metastatic urothelial transitional cell carcinoma. This phase I study assessed the effect of renal impairment on the pharmacokinetics and tolerability of VFL. Methods VFL was infused in patients with advanced/metastatic solid tumours once every 3 weeks with anticipated dose reduction on the first cycle stratified according to the creatinine clearance (CLcr) values. Pharmacokinetic data were collected on the first two cycles in renally impaired patients (CLcr ≤ 60 ml min-1) and were compared with a control cohort of patients (CLcr > 60 ml min-1). Results Thirty-three patients (46-86 years) were treated, 13 in group 1 (40 ml min-1 ≤ CL cr ≤ 60 ml min-1) and 20 in group 2 (20 ml min -1 ≤ CLcr < 40 ml min-1). The renal dysfunction induced a mean decrease in VFL clearance of 12% in group 1 and 28% in group 2, compared with the control group. The anticipated dose reduction given in renally impaired patients (i.e. 280 mg m-2 and 250 mg m -2 in groups 1 and 2, respectively) yielded similar drug exposure to control patients. The tolerance profile of VFL in patients with renal dysfunction was similar to that observed in patients with CLcr > 60 ml min-1. Conclusion In conclusion, the recommended doses of intravenous VFL administered once every 3 weeks in cancer patients with renal impairment are 280 mg m-2 when CLcr is between 40 and 60 ml min-1 and 250 mg m-2 when CLcr is between 20 and <40 ml min-1. © 2013 The British Pharmacological Society.


Rossi C.,Hematologie CliniqueRene Olivier Casasnovas | Kanoun S.,Center Gf Leclerc | Berriolo-Riedinger A.,Center Gf Leclerc | Dygai-Cochet I.,Center Gf Leclerc | And 6 more authors.
Journal of Nuclear Medicine | Year: 2014

PET performed after 2 cycles of chemotherapy (PET2) allows prediction of outcome in most patients with Hodgkin lymphoma (HL). Visual analysis using a 5-point scale was proposed to assess PET response, but a semiquantitative approach using maximum standardized uptake value (SUVmax) reduction between baseline and interim PET was shown to be superior to the 5-point scale in patients with diffuse large B-cell lymphoma and may also improve the accuracy of interim PET interpretation in HL. To compare the clinical usefulness of both methods in HL patients, we analyzed PET2 according to visual and δSUVmax criteria in a retrospective singlecenter study. Methods: From 2007 to 2010, 59 consecutive patients with a first diagnosis of HL were treated with 4-8 cycles of anthracycline- based chemotherapy. Radiotherapy was performed in 19 responding patients with localized disease. PET was done at baseline (PET0) and after 2 cycles of chemotherapy, and treatment was not modified according to the PET2 result. PET2 was interpreted using the 5-point scale (positivity for score 4 or 5). The SUVmax reduction between PET0 and PET2 (δSUVmax) was computed for all patients, and patients with a δSUVmax greater than 71% were considered good responders. Results: When the 5-point scale was used, 46 patients (78%) achieved a negative PET2 result, 7 of whom failed treatment (negative predictive value, 85%). Forty-nine patients (83%) had a δSUVmax greater than 71%, 6 of whom failed treatment (negative predictive value, 88%). The PET2 positive predictive value was significantly better for δSUVmax (70%) than for the 5-point scale (46%). When δSUVmax was used, 6 (46%) of the 13 PET2- positive patients could be reclassified as good responders. Although visual PET2 positivity was related to a lower 4-y progression-free survival (45%) compared with PET2 negativity (81%, P > 0.002), DSUVmax (<71 vs ≥71%) was more accurate for identifying patients with different 4-y progression-free survivals (82% vs. 30%; P , 0.0001). In multivariate analysis using the international prognosis score and DSUVmax as covariates, DSUVmax remained the unique independent predictor for progression-free survival (P > 0.0001; relative risk, 8.1). Conclusion: Semiquantitative analysis was more accurate than visual analysis based on the 5-point scale to interpret PET2 and predict the outcome of HL patients. These encouraging results warrant further confirmation in larger and prospective series. © 2014 SNMMI; all rights reserved.


PubMed | Center Gf Leclerc
Type: Clinical Trial, Phase I | Journal: British journal of clinical pharmacology | Year: 2014

Vinflunine (VFL) ditartrate, a novel tubulin-targeted inhibitor, is registered for the treatment of patients with advanced or metastatic urothelial transitional cell carcinoma. This phase I study assessed the effect of renal impairment on the pharmacokinetics and tolerability of VFL.VFL was infused in patients with advanced/metastatic solid tumours once every 3 weeks with anticipated dose reduction on the first cycle stratified according to the creatinine clearance (CLcr ) values. Pharmacokinetic data were collected on the first two cycles in renally impaired patients (CLcr 60mlmin(-1) ) and were compared with a control cohort of patients (CLcr > 60mlmin(-1) ).Thirty-three patients (46-86 years) were treated, 13 in group 1 (40mlmin(-1) CLcr 60mlmin(-1) ) and 20 in group 2 (20mlmin(-1) CLcr < 40mlmin(-1) ). The renal dysfunction induced a mean decrease in VFL clearance of 12% in group 1 and 28% in group 2, compared with the control group. The anticipated dose reduction given in renally impaired patients (i.e. 280mgm(-2) and 250mgm(-2) in groups 1 and 2, respectively) yielded similar drug exposure to control patients. The tolerance profile of VFL in patients with renal dysfunction was similar to that observed in patients with CLcr > 60mlmin(-1) .In conclusion, the recommended doses of intravenous VFL administered once every 3 weeks in cancer patients with renal impairment are 280mgm(-2) when CLcr is between 40 and 60mlmin(-1) and 250mgm(-2) when CLcr is between 20 and <40mlmin(-1) .

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