Bevacizumab combined with 5-FU/streptozocin in patients with progressive metastatic well-differentiated pancreatic endocrine tumours (BETTER trial)--a phase II non-randomised trial.

AIM OF THE STUDY: Neuroendocrine tumours are highly vascular neoplasms known to overexpress vascular endothelial growth factor (VEGF) and its receptor. Bevacizumab, an inhibitor of VEGF, was assessed in combination with chemotherapy in pancreatic neuroendocrine tumour (P-NET). PATIENTS AND METHODS: BETTER was a multicentre, open-label, non-randomised, two-group phase II trial. Patients with progressive metastatic, well-differentiated P-NET received a minimum of 6 month treatment of bevacizumab at 7.5 mg/kg IV on d1 q3w with 5-FU at 400 mg/m2/day and streptozocin at 500 mg/m2/day IV from d1 to d5 every 42 days. The primary end-point was progression-free survival (PFS); secondary end-points were overall survival (OS), overall response rate, safety and quality of life. RESULTS: A total of 34 patients were included. Median age was 55 years, 65% of patients were men, 97% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and 97% had a Ki-67 proliferative index of <15%. After a maximum of 24 month follow-up per patient, the median PFS assessed by investigators was 23.7 months [95% confidence interval (CI): 13.1; not reached], 19 (56%) patients had a partial response and 15 (44%) had stable disease as best response. OS rate at 24 months was 88%. The most frequently reported grade 3-4 adverse events were hypertension (21% patients), abdominal pain (12%) and thromboembolic events (9%). CONCLUSION: Bevacizumab with 5-FU/streptozocin in the treatment of pancreatic NETs seems to be feasible with a PFS of 23.7 months, which deserves further attention. No unexpected toxicity was observed.

Anaemia management with C.E.R.A. in routine clinical practice: OCEANE (Cohorte Mircera patients non-dialyses), a national, multicenter, longitudinal, observational prospective study, in patients with chronic kidney disease not on dialysis.

OBJECTIVE: The aim of this study was to describe the management of anaemia with a continuous erythropoietin receptor activator (C.E.R.A., methoxy polyethylene glycol epoetin-ß), in patients with chronic kidney disease (CKD) not on dialysis, naïve or non-naïve to treatment with erythropoiesis-stimulating agents (ESAs) at inclusion. DESIGN: National, multicentre, longitudinal, observational prospective study. SETTING: 133 nephrologists practicing in France selected patients during their routine follow-up visits. The study was non-interventional. PARTICIPANTS: They were adult CKD patients not on dialysis or kidney transplant patients, naïve or not to ESA treatment: 524 patients not on dialysis (48% ESA-naïve) and 92 kidney transplant patients (24% ESA-naïve) were included and followed up every 3 months during 1 year. OUTCOME MEASURES: The two main endpoints were the percentage of patients who achieved target haemoglobin (Hb) levels as per European Medicines Agency guidelines (10-12 g/dl) around 6 months of treatment and modalities of treatment. RESULTS: Approximately one in two patients had an Hb level within 10-12 g/dl at baseline, and around 6 and 12 months of treatment. Ninety per cent of ESA-naïve patients achieved at least +1 g/dl increase over baseline Hb levels or had Hb within 10-12 g/dl around 6 and 12 months. The Hb level remained at approximately 11.5 g/dl during the 12 months of follow-up. Around 6 months: almost all patients were receiving a once-monthly subcutaneous dose of C.E.R.A. (patients not on dialysis: 95±54 µg; kidney transplant patients: 121±70 µg); approximately half the patients did not require a change in C.E.R.A. dose. Adverse effects related to C.E.R.A. were observed in less than 5% of patients and led to modification or discontinuation of treatment in 2%. CONCLUSIONS: The efficacy and safety of C.E.R.A. in CKD patients not on dialysis, with or without kidney transplantation, were confirmed in routine clinical practice.

[Anemia management in French hemodialysis patients: DiaNE study results at 3 years (DiaNE2)]. / Prise en charge de l'anémie des patients hémodialysés en France : résultats de l'étude DiaNE à trois ans (DiaNE 2).

The observational study DiaNE provides a current state of anemia management with Epoetine bêta in hemodialysis patients regarding European recommendations over a 3-year period in France. Patients still treated with Epoetine bêta twelve months after their inclusion in DiaNE were eligible for a 24-month extension phase entitled DiaNE 2. Data regarding 439 patients followed during three years, from M0 to M36, were analyzed. Hemoglobin (Hb) level of the cohort remained over the target value of 11g/dL during the study (M0: 11.3±1.2g/dL; M36: 11.8±1.3g/dL). The anemia management had evolved with European recommendations updates and was in accordance with the last recommended target range (11-12g/dL) in a third of patients. During the follow-up, the majority of patients (97%) had at least one modification of treatment with Epoetine bêta (change in frequency of injections, adjustment of doses) mainly justified by excursion of Hb level out of the target range. However, the median dose of Epoetine bêta was relatively stable. The number of patients with iron treatment remained stable (60%). In spite of undertaken efforts, anemia management of hemodialysed patients in France still needs optimization for maintaining Hb level in the recommended target range.

[Is the management of anemia in hemodialysis patients improving in France? Results of the DiaNE study]. / La prise en charge de l'anémie du patient hémodialysé en France s'améliore-t-elle? Résultats de l'étude DiaNE.

French and international clinical practice guidelines recommend a minimum hemoglobin level of 11 g/dl in patients with chronic kidney disease. Previous studies implemented between 1996 and 2003 showed that only 35 to 55% the patients reach this target. Dialysis NeoRecormon Epidemiology (DiaNE) is a one-year French multicentric observational study designed to follow a cohort of 1200 patients with ESRD treated with epoetin beta to assess the management of anemia in routine nephrologic practice. From December 2003 to September 2004, 1241 hemodialysis patients were recruited by 229 centers. At baseline, 64.4% of patients had hemoglobin levels greater than 11 g/dl. The proportion of patients with hemoglobin levels greater than 11 g/dl at the end of the study was 71.6%. These results could be partly explained by iron deficiency: 46% of patients had a serum ferritin between 200 and 500 microg/l and about one third of patients had a transferrin-iron saturation percentage greater or equal to 30% at baseline and at the end of the study. Epoetin beta was administrated by subcutaneous route in 65.5% of patients with similar efficacy and with less mean doses than intravenous route (114.6+/-81.5 IU/kg versus 146.5+/-124.3 IU/kg at the end of the study). In conclusion, the management of anemia in hemodialysis patients is not optimal but is slightly better than the management observed between 1996 and 2003. Iron and inflammatory status should be taken into account to improve the efficacy of anemia therapy using erythropoietin-stimulating agents.