Chemotherapy and biotherapy in the treatment of neuroendocrine tumours.

The medical treatment of neuroendocrine GEP tumours must be based on the growth properties of the tumour. Medical treatment includes chemotherapy, somatostatin analogues and alpha interferons. Chemotherapy has been particularly active in patients with high proliferating neuroendocrine tumours such as endocrine pancreatic tumours and lung carcinoids. Streptozotocin-based combinations including 5-flourouracil and doxorubicin have generated partial remissions in 40%-60% of the patients giving a median survival of about two years in patients with advanced disease. Cisplatinum plus etoposide have demonstrated significant antitumour effects in anaplastic endocrine pancreatic tumours and lung carcinoids. However, in low proliferating tumours such as classical midgut carcinoids the response rates with the same combinations of cytotoxic agents have only generated short lasting responses in less than 10% of patients. In these patients, biological treatment has been of benefit. Alpha interferon at doses of 3-9 million units three to seven times per week subcutaneously, has given biochemical response rates of 50% and significant tumour reduction in about 15% of patients with long duration, up to three years. Somatostatin analogues have been widely used in the treatment of neuroendocrine gut and pancreatic tumours. The currently available somatostatin analogues particularly bind somatostatin receptor 2 and 5 and with low affinity also receptor subtype 3. Octreotide is registered in most countries for the treatment of patients with carcinoid syndrome and also VIP and glucagon producing tumours. Regular octreotide at standard doses of 100-300 microg/day gives symptomatic responses in a medium of 60% of patients and biochemical responses in up to 70% of patients. Significant tumour responses are rare, less than 5%. Long-acting formulations of somatostatin analogues have been of significant benefit for the patients with similar response rates as for regular formulations. The quality of life has been significantly improved by using the long-acting formulations.