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Dijon, France

Penault-Llorca F.,Center Jean Perrin | Vincent-Salomon A.,University Pierre and Marie Curie | Bellocq J.-P.,Service dAnatomie Pathologique | Matthieu M.-C.,Institute Gustave Roussy | And 24 more authors.
Annales de Pathologie

In Europe, patients who may benefit from an HER2 targeted drug are currently selected by immunohistochemistry (IHC). In situ hybridization (ISH) techniques should be used for complementary assessment of ambiguous 2+ IHC cases and for the calibration of the IHC technique. Eligibility to an HER2 target treatment is defined by an HER2 positive status being IHC test 3+ or 2+ amplified. Reliable detection of HER2 status is essential to the appropriate usage of HER2 targeted drugs because its specificity is limited to tumors overexpressing HER2. It is essential that the IHC evaluation of the HER2 status of a mammary carcinoma is optimized and reliable. This GEFPICS' guidelines look over the different steps of the IHC technique, the controls and, the rules for interpretation. Once acquired, this knowledge must be perpetuated by the observation of rules of good technical practice (internal and external controls, quality assurance programs). © 2010 Elsevier Masson SAS. Source

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

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. Source

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.

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. Source

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

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. Source

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

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. Source

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