European experience of 6-thioguanine for azathioprine intolerance in Crohn’s disease

Current treatment for midgut carcinoid includes radical surgery of the primary tumour, resection of lymph node metastases and resection of liver metastases. In the presence of disseminated disease however, cure is unusual. Palliative liver resection and hepatic artery embolisation are also recognised to decrease hormone secretion and reduce tumour volume. Somatostatin analogues reduce the synthesis and secretion of neuropeptides so reducing hormonal symptoms in up to 80% of patients. Alpha interferon has been previously shown to reduce urinary 5HIAA levels in carcinoid patients. In a previous Norwegian study a survival advantage was shown for patients treated with alpha interferon in combination with hepatic arterial embolisation. This present study was therefore carried out to identify the effect of alpha interferon added to a somatostatin analogue on survival and tumour progression after initial tumour reduction by surgery and embolisation for disseminated mid gut carcinoids. Sixty eight patients were treated with maximum tumour reduction and underwent hepatic artery embolisation followed by randomisation to either treatment with octreotide or a combination of octreotide and alpha interferon. All patients had liver metastases. The overall five year survival rate was 66%. Although there was no significant difference in survival between patients treated with octreotide alone (five year survival rate 37%) and those given octreotide in combination with alpha interferon (five year survival rate 57%), patients treated with alpha interferon had a significantly reduced risk of tumour progression during follow up (p = 0.008). This was a relatively small but very important study which demonstrates that alpha interferon may have a role in inhibiting tumour growth in patients with disseminated midgut carcinoid who have undergone debulking surgery and hepatic embolisation. Hopefully further larger studies with quality of life assessments included will be forthcoming.