An high-dose treatment with lanreotide (up to 12 mg/day) GSK2245840 purchase produced tumour size reduction in 5% and stabilisation in 70% of the 19 patients. In responding patients was observed an induction of apoptosis in the tumours, a phenomenon not seen with regular

doses of somatostatin analogs, but often produced by chemotherapeutic agents [62]. Subcutaneously injections of 5 mg lanreotide three times a day for a period of 1 year produced one complete and one partial remission in 30 patients with functional midgut NETs; stable disease in 11 patients (36%) and progression of the disease after 3-12 months of treatment in 11 patients [63]. The treatment with high-dose somatostatin analogues induced apoptosis in neuroendocrine tumours, while this was not found during treatment with low-dose somatostatin, in a study where biopsy specimens were taken before and during somatostatin analogue treatment [61]. In a highly select group of patients with progressive disease, 47% of the patients demonstrated at least stable disease when treated with

a high dose of lanreotide (3-5 g/day) [77]. High-dose formula of octreotide has Rabusertib solubility dmso been recently reported to stabilize hormone production and tumour growth in 75% of patients with advanced midgut carcinoid tumours and progressive disease with stabilisation for 6-24 months, [78]. These effects may be attributable to SSTR 2 which is the most frequently expressed subtype and/or SSTR 5, 1 and 3 which are also expressed [90, 91]. Data from a study with Y-27632 in vitro ultra-high dose octreotide pamoate (Onco-LAR; Novartis) at 160 mg intramuscularly every 2 weeks for 2 months followed by the same dose once monthly, appear to show some promise. Ceramide glucosyltransferase Tumour size stabilisation was obtained in 12 patients, a biochemical responses in 9 patients and/or stability in 11. No significant tumour reduction was noted. At 6 months, the median plasma concentrations

of octreotide were 25-100 times higher than those obtained by using octreotide LAR at regular doses. A significant inhibition of angiogenesis was also showed through the down-regulation of proliferative factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor [12]. The highest response rates were reported using octreotide in doses greater than 30 mg/day or lanreotide in doses greater than 5 mg/day (and up to 15 mg/day) [63]. Tomassetti et al. have reported that after one-year therapy, the tumour completely disappeared in three patients suffering from gastric carcinoid, two of whom were treated with lanreotide 30 mg i.m. every 10 days [92].