SummaryObjective This prospective randomized study evaluated the efficacy and safety of octreotide LAR vs. surgery in newly diagnosed acromegalic patients.Methods Totally 104 male and female patients were enrolled in a 50‐week, exploratory, open‐label and randomized study. Eligible patients were randomized to receive either octreotide LAR 20 mg every 28 days or to undergo surgery. Efficacy was assessed by changes in mean GH and IGF‐I serum concentrations, at weeks 12, 24 and 48. Tumour volume was assessed by contrast‐enhanced MRI. In both groups, treatment adjustment was performed for patients uncontrolled at week 12 or 24. Octreotide LAR patients received a dose increased to 30 mg or, if already receiving this dose, investigator and patients could decide to cross‐over to surgery. Patients uncontrolled after surgery received octreotide LAR 20 mg, increased to 30 mg if acromegaly was still uncontrolled.Results Overall success rates at weeks 24 and 48 were 25% and 28% for the octreotide LAR group and 49% and 39% for the surgery group. Only the difference observed at week 24 was statistically significant (P = 0·047). Both groups had a significant (> 20%) tumour shrinkage: 73% of patients in the octreotide LAR group and 95% in the surgery group. Major differences between octreotide LAR and surgery group in the occurrence of adverse events were gastrointestinal (71%vs. 27%), hepatobiliary (41%vs. 8%) and respiratory (5%vs. 28%).Conclusion This first randomized study in unselected patients indicates that the 48‐week treatment outcome of octreotide LAR as first‐line treatment of acromegaly does not significantly differ from surgery. As a complete response to surgery in GH‐secreting macro‐adenomas can be difficult, first‐line therapy with octreotide LAR can be considered as a viable alternative for most patients with acromegaly, due to its low complication rate.

Objective To evaluate the efficacy, safety and tolerability of octreotide LAR((R)) (long-acting repeatable octreotide) in the primary therapy of acromegaly.Design and patients Ninety-eight previously untreated acromegalics were recruited into this prospective multicentre study. A total of 68 patients successfully completed 48 weeks of the study period, received 12 doses of octreotide LAR 10-30 mg every 4 weeks, and constituted the population used for this analysis.Measurements and results A clinically relevant reduction (i.e. to <= 5 mu g/l) in mean GH (mGH) was recorded in 72% of patients after 24 weeks of treatment, and 42% reached a 'safe' GH value (<= 2.5 mu g/l). At week 48, 16 more patients were considered partial GH responders (GH > 2.5 mu g/l and <= 5 mu g/l) and 44% had reached a GH level <= 2.5 mu g/l. IGF-1 levels normalized in 38% and 34% of patients after 24 and 48 weeks of treatment, respectively. At study completion, 10 patients (14.7%) who had not normalized their IGF-1 levels had achieved at least a 50% decrement in this marker. In eight microadenoma patients, tumour volume decreased from a mean baseline level of 298 +/- 145 mm(3) to 139 +/- 94 mm(3) after 24 weeks and to 99 +/- 70 mm(3) after 48 weeks of therapy. In 60 patients with macroadenoma, the corresponding values were 3885 +/- 5077 mm(3) at baseline and 2723 +/- 3435 and 2406 +/- 3207 mm(3) after 24 and 48 weeks, respectively. At weeks 24 and 48, a significant (> 20%) tumour volume reduction was reported in 63% and 75% of patients, respectively. A reduction in the severity of symptoms of acromegaly was observed early in treatment and was maintained throughout the study period.Conclusion Octreotide LAR represents a viable alternative to surgery for primary treatment of acromegaly leading to a progressive regression of tumour volume, a sustained control of biochemical abnormalities and an adequate relief of symptoms of the disease.

To assess whether the prognostic significance of cardiovascular (CV) biomarkers, is affected by renal dysfunction (RD) in systolic heart failure (HF).It is unknown, whether the prognostic significance of CV biomarkers, such as N-terminal-pro-brain-natriuretic-peptide (NT-proBNP), high-sensitive troponin T (hsTNT), pro-atrial natriuretic peptide (proANP), copeptin and pro-adrenomedullin (proADM), is affected by renal function in HF.Clinical data and laboratory tests from 424 patients with systolic HF were collected prospectively. The patients were followed for 4.5 years (interquartile range: 2–7.7 years). CV biomarkers were analyzed on frozen plasma, and renal function was estimated by the Modification of Diet in Renal Disease (MDRD) formula. Cox proportional hazard models for mortality risk were constructed and tests for interaction between each CV biomarker and RD were performed.Median age was 73 years (51–83), 29% were female, LVEF was 30% (13–45), 74% were NYHA classes I–II and estimated glomerular filtration rate (eGFR) was 68 ml/min/1.73 m2 (18–157). A total of 252 patients died. All five biomarkers – log(NT-proBNP) (HR: 2.13, 95% CI: 1.57–2.87:, P < 0.001), hsTNT (HR: 3.07, 95% CI: 1.90–4.96 P < 0.001), proANP (HR: 1.02, 95% CI: 1.01–1.03, P < 0.001), copeptin (HR: 1.02, 95% CI: 1.01–1.03, P = 0.008) and proADM (HR: 2.37, 95% CI: 1.66–3.38, P < 0.001) – were associated with mortality risk, but not affected by RD (P > 0.05 for all interactions).Established and new CV biomarkers are closely associated with renal function in HF. However, their prognostic significance is not affected by RD, and all CV biomarkers can be used for risk stratification independently of renal function.

Introduction: For (GH) producing adenomas, transphenoidal surgical resection is the treatment of first choice. However, patients with invasively growing macroadenomas, especially those with extrasellar extension, have a poorer prognosis: surgical cure can generally be achieved in fewer than 50% of patients. To assess the efficacy and safety of primary therapy with octreotide LAR versus surgery in previously untreated acromegalic patients, a prospective, randomized, multicentre, clinical study was performed. Methods: A total of 104 male or female patients, with untreated acromegaly, were enrolled in this 50-week, randomized study. Patients were treated with either octreotide LAR 20mg every 4 weeks, or surgery. Mean GH and IGF-I serum concentrations at weeks 12, 24 and 48, were used to evaluate the biochemical response to treatment. Tumor volume (centrally evaluated by MRI) was assessed at weeks 24 and 48. Dose adjustment and cross-over was allowed according to treatment response at weeks 12 and/or 24. Results: In contrast to the surgery group, patients randomized to octreotide LAR had at baseline a lower mean age, and approximately twice higher mean serum GH concentration and tumor volume.

Background: Somatostatin analogues are the standard medical therapy for acromegaly. There is significant interest in how the use of different treatment regimens (e.g. surgery, medical therapy) impacts the clinical course of disease. This study has been designed to better understand clinical decision making in the context of various treatment options.

14097 Background: Because of their efficacy and safety profile, somatostatin analogues have become the preferred medical therapy for symptom control in functioning GEP tumors. There is significant medical interest on how the use of different treatment regimens in GEP tumor patients may impact the clinical course of the disease. The objectives of this study are to describe the clinical decision making in context of a medical treatment with a chosen dose of Sandostatin LAR, and to identify optimal dosing regimens which may lead to improved patient outcomes. Methods: GEPTOSIS (Neuroendocrine GEP Tumors: An Observational Study on the Impact of Sandostatin LAR) is an open label, multicenter, non-comparative, longitudinal, observational study in recently diagnosed, previously medically untreated, functionally active GEP neuroendocrine tumors (NET) such as carcinoid, insulinoma or glucagonoma. Observations will include the efficacy on biochemical parameters (Chromogranin A, 5-HIAA) and symptoms (flush and diarrhea), effect on tumor volume, safety and tolerability. Data are entered via a Palm based device and transferred to a central study database accessible by the study centers via a web-based study portal. Data from each patient will be collected under (conditions of) normal clinical practice in quarterly intervals over a period of 18 months. This study is planned to recruit up to 1500 patients and will involve about 300 sites world-wide. Results: At time of abstract submission, 133 sites have committed to enroll 495 patients and further sites are being recruited to meet the targeted 1500 patients. Results of a first interim analysis will be presented. Conclusions: With increasing enrollment into the GEPTOSIS study, more data on prescribing and dosing patterns in recently diagnosed GEP NET patients are expected to be available throughout 2006. [Table: see text]

Introduction: In this open-label, prospective multicenter study, the safety, efficacy, and tolerability of octreotide LAR as primary therapy of acromegaly was investigated. Methods: A total of 98 out of 110 screened patients entered treatment. Patients were treated for 48 weeks, and 68 patients (8 microadenoma, 60 macroadenoma) entered the final analysis, regardless of response to treatment. A dose adjustment based on mean GH and IGF-1 was performed after 4 doses of octreotide LAR 20mg, and patients were then treated with doses of 10, 20 or 30mg for an additional 32 weeks (8 doses). Results: The following table shows mean 2-hour GH and IGF-1 levels at baseline and after 48 weeks of therapy.

Single-dose pharmacokinetic (PK) profiles and multiple-dose PK modeling were compared for long-acting octreotide (20 or 60 mg) and prolonged-release lanreotide (90 or 120 mg) over 91 days; steady-state profiles were simulated. All treatments were well tolerated. Octreotide 20-mg profile showed increased concentration on clay 1, lag from days 2 to 6, then prolonged plateau phase (days 11-41); 60-mg PK was dose proportionol. Lonreotide 90-mg profile showed C-max on day 1 then elimination (apparent t(1/2) 25.5 days); 120-mg profile was underproportional. Steady-state PK of octreotide 20 mg/28 d suggested a C-mean of 1216 pg/mL (range, 1065-1585) with low fluctuation index (43%). Steady-state PK of lanreotide 90 mgl 28 d suggested a C-mean of 4455 pglmL (range, 2499-9279) with high fluctuation index (152%). Long-acting octreotide had more predictable PK than prolonged-release lanreotide. Simulated steady-state profiles suggest long-acting octreotide could be optimized to meet individual patient needs. In contrast, proloned-release lanreotide requires exposure canstantly above the therapeutic target to enable monthly long-term therapy.