Moreover, an increase of the dosage of somatostatin analogs seems to have a better control both of the disease progression and the chronic refractory diarrhea [24]. Somatostatin MK-8931 order analogues and interferon The combination of SSAs and interferon (IFN) has been used in an effort to enhance the antiproliferative effect of interferon therapy, to add the positive effect of SSAs on hypersecretory syndromes, and to reduce the dose of IFN and thus the number of IFN-related side-effects. Whether somatostatin analogues and IFN show a synergistic effect on tumour growth and in carcinoid syndrome symptom management is matter of debate. The combination therapy with somatostatin

analogues and IFN is MLN2238 mouse in BI2536 fact limited by the small number of trials, with variable results. This combination seems of benefit in patients where the usual octreotide treatment failed to achieve a biochemical and symptomatic control [93]. This combination therapy leaded to a significantly lower risk of progressive disease compared with somatostatin analogues alone, and had a higher median survival (51 vs 35 months) [94]. An anti-proliferative effect of the addition of α-interferon to octreotide was showed in a subgroup of patients with advanced metastatic disease unresponsive to octreotide monotherapy,

and prolonged survival was reported in the responder group [95]. However, most published data do not support a major effect of interferons over and above that of somatostatin analogues. In a prospective multicenter study on the effect of combination therapy, Faiss et al showed no advantage on either biochemical or antiproliferative results, while the number of side-effects increased [96]. Novel somatostatin analogues Recently the universal or “”pan-receptor”" somatostatin ligand pasireotide (SOM230) has been developed, which possess high affinity binding to SSTs 2, 3 and 5, moderate affinity for SSTR 1. Its receptor binding profile

is 30- Thalidomide to 40-times higher for SSTR 1 and SSTR 5 than octreotide. In a multicentre study on metastatic carcinoid tumours patients whose symptoms (diarrhoea and flushing) were refractory to octreotide-LAR, pasireotide at dosages between 450 μg and 1200 μg twice a day effectively controlled symptoms in 33% of these patients [97]. These results support the hypothesis that pasireotide may have potential in the treatment of these tumours. Subtypes of somatostatin and dopamine receptors may form homo- and hetero-dimers at the membrane level, and this receptor “”association”" may be induced by addition of either dopamine or somatostatin. Recently, subtype selective analogues and antagonists, as well as bi-specific and hybrid somatostatin/dopamine compounds, binding to SSTR 2, SSTR 5 and dopamine 2 receptors have been developed [98].