Histoire naturelle des cancers de prostate de haut grade

Prostate cancer, in men, is the most common cancer after 50 years old and the second cause ofall cancer deaths. Overall survival reaches 77 % at 5 years and it depends on several prognostic factors including Gleason score. Few epidemiological data are available regarding high-grade tumors This study has been conducted in order to describe their natural history. We retrospectively included all patients who had biopsies analyzed in the referent pathology laboratory of the Bergonie institute, and who had developed a prostate cancer with a majority Gleason grade higher or equal to 4, between January 2003 and December 2006. The evolution of the population has been studied until the end of 2009. The characteristics of patients and tumors at diagnosis, the time to relapse and to develop hormone-refractory, the treatment at relapse and the response to chemotherapy have also been analyzed. 119 patients were included, with a mean age at diagnosis of 72,4 years, 55,6 % of diagnosis were made by the systematic screening, 27,6 % of patients had metastases at diagnosis especially at bone sites (93,1 %. The median time to relapse, either biological or metastatic, and development of hormone-refractory were respectively 5,22 and 6,1 years. The response rate to chemotherapy was 40,7 % with a median survival of 1,23 year. These results show that the isolated histological character of high-grade does not seem to worsen the prognosis of these patients and their relapse rate is not different from that of other tumors at high risk. However, they remain aggressive with a high risk of local and metastatic progression. Should we then consider these high-grade tumors as a special group which needs particular investigation of biological characteristics and special treatments protocol ?Chez l'homme le cancer de la prostate est le plus fréquent après 50 ans et il est la 2ème cause de décès par cancer. La survie gllobale est de 77 % à 5 ans mais elle dépend de plusieurs facteurs pronostiques dont le score de Gleason. Peu de données épidémiologiques sont disponibles concernant les tumeurs de haut grade. Nous avons réalisé cette étude pour décrire leur histoire naturelle. Nous avons inclus rétrospectivement tous les patients ayant eu des biopsies analysées au laboratoire d'anatomopathologie référent pour l'institut Bergonié, entre janvier 2003 et décembre 2006, et pour lesquels l'examen a révélé un adénocarcinome prostatique avec un grade de Gleason majoritaire supérieur ou égal à 4. Nous avons étudié l'évolution de cette population jusqu'à la fin de l'année 2009. Nous avons également décrit les caractéristiques des patients et des tumeurs au diagnostic, le délai de rechute et d'hormono-résistance, leur prise en charge à la rechute et la réponse à la chimiothérapie mise en place. Sur 119 patients inclus, avec un âge moyen au diagnostic de 72,4 ans, le dépistage systématique est à l'origine des diagnostics. 27,6 % des patients sont métastatiques au diagnostic avec 93,1 % de localisations osseuses. Les délais médians de survenue de la rechute biologique et/ou métastatique et de l'hormono-résistance sont respectivement de 5,22 ans et de 6,1 ans. Le taux de réponse à la chimiothérapie est de 40,7 % avec une médiane de survie de 1,23 ans. Ces résultats montrent, de façon assez inattendue, que le caractère isolé de haut grade ne semble pas aggraver le pronostic de ces patients et que le taux de rechute n'est pas didférent de celui des tumeurs de haut risque. Cependant elles restent agressives avec un risque élevé d'évolution loco-régionale et métastatique. Faut-il alors considérer ces tumeurs de haut grade comme un groupe à part et rechercher leurs caractéristiques biologiques propres afin de trouver des traitements mieux adaptés à leur prise en charge ?BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Axitinib: A Review of its Safety and Efficacy in the Treatment of Adults with Advanced Renal Cell Carcinoma

Over the last seven years, seven targeted agents have been approved in the treatment of advanced or metastatic renal cell cancer, changing the therapeutic approach and prognosis of the disease dramatically. The latest agent with demonstrated efficacy is axitinib (Inlyta®). This new generation of tyrosine kinase agent differs from previously existing agents by its greater activity potency of inhibition of vascular endothelial growth factor-receptor (VEGFR1-3). This efficacy has been tested in phase II and III clinical trials. Axitinib is the only targeted agent that benefits from recommended titration, with intra-patient dose escalation. The toxicity profile of the drug is tolerable. This paper reviews the mechanism of action of axitinib, its metabolism, and its pharmacokinetic profile. Clinical data of efficacy and safety is also detailed. The agent has been integrated in the international therapeutic guidelines, as a standard in treatment of renal cell cancer patients, previously treated through antiangiogenic therapy

The impact of sarcopenia on the efficacy and safety of immune checkpoint inhibitors in patients with solid tumours

Background : Evidence suggests that sarcopenia is a significant predictive factor of worst outcomes and treatment-associated toxicities in patients with metastatic solid tumours. The aim of this study was to explore the relationship between low muscle mass and clinical outcomes and immune-related severe toxicities (IrST) in patients treated with immune checkpoint inhibitors (ICIs). Methods : A retrospective cohort of 261 consecutive metastatic solid tumour patients treated with ICIs were included in our study. Low muscle mass was defined as skeletal muscle index <41 cm2/m2 for females and <43 cm2/m2 for males if body mass index (BMI) <25 kg/m2 or <53 cm2/m2 if BMI ≥ 25 kg/m2. Severe toxicities (ST), including grade III-IV toxicities and side effects leading to treatment interruption, were recorded. Results : The majority of patients (n = 179; 69%) included in this study had metastatic lung cancer. The prevalence of low muscle mass was 47%. The median progression-free survival (PFS) was 32.2 weeks for low muscle mass patients and 24.3 weeks for non-low muscle mass patients (adjusted HR, 0.80; 95% CI, 0.60–1.055; p = 0.11). For low muscle mass and non-low muscle mass lung cancer patients, median PFS was 24.0 weeks and 18.8 weeks (adjusted HR, 0.70; 95% CI, 0.50–0.98; p = 0.04) and median overall survival was 50.7 weeks and 41.1 weeks (adjusted HR, 0.77; 95% CI, 0.54–1.10, p = 0.15) respectively. Immune-related severe toxicities occurred in 3.3% and 9.4% of low muscle mass and non-low muscle mass patients respectively (adjusted OR, 0.69; 95% CI: 0.31–1.49; p = 0.35). Conclusion : No difference in outcomes and safety was observed for low muscle mass and non-low muscle mass patients treated with ICIs

Early objective response may not be a prognostic factor of survival for patients with metastatic urothelial carcinoma: from a retrospective analysis of a cohort of 113 patients

International audienceBackground: This study aims to better define prognostic factors for patients with metastatic urothelial carcinoma (mUC), and to identify patients who will benefit from first-line cisplatin-based chemotherapy. We test the hypothesis that early objective response (EOR), defined as the occurrence of an objective response following 2 or 3 courses of chemotherapy, could be a prognostic factor for overall survival (OS) and thus be used to guide treatment decisions. Data from 113 patients with evaluable mUC receiving first-line cisplatin-based treatment between January 2004 and December 2006 was collected retrospectively from prospectively-maintained databases across seven French cancer centers. Clinical factors potentially associated with survival and EOR were analyzed in univariate and multivariate analysis. Results: One hundred three patient records were complete and available for inclusion in the multivariate model. Four factors were independently associated with OS: Performance status 1 and 2 (HR 2.3 [95 % CI 1.3–3.9], p = 0.002; HR 3.4 [95 % CI 1.6–7.2], p = 0.001 respectively); presence of visceral metastases (HR 2.2 [95 % CI 1.3–3.9], p = 0.004); abnormal hemoglobin levels (HR 1.7 [95 % CI 1.01–2.8], p = 0.045); disease progression (HR 10.1 [95 % CI 4.2–24.1], p < 0.001)

Aide à la décision de transfert ou non transfert en réanimation d’un patient atteint de cancer

Référentiel inter régional en soins oncologiques de support, AFSOS et Réseau Espace Santé - Cancer Rhône-Alpes (RRCRA), 201