INTERFERONS ALONE OR IN COMBINATION WITH CHEMOTHERAPY OR OTHER BIOLOGICALS IN THE TREATMENT OF NEUROENDOCRINE GUT AND PANCREATIC TUMORS

The treatment of malignant neuroendocrine gut and pancreatic tumors pr ovides a therapeutic challenge. Surgery as well as medical treatment r arely cure the patient at this stage. Symptoms related to secretory pr oducts from the tumor might be life-threatening or at least reduce the quality of life considerably. Interferons (IFNs) have demonstrated an antitumor effect in multiple tumor diseases and were introduced by ou r group in 1982 for the treatment of carcinoids. Today, more than 300 patients with various neuroendocrine tumors and who receive alpha-IFN have been reported in the literature. Treatment of midgut carcinoid tu mors at doses of 3-9 MU 3-7 times per week subcutaneously has achieved biochemical responses in 44% of the patients with significant tumor r eduction in 11%. Subjective improvement has been obtained in around 65 % of the patients. A median survival from start of treatment in patien ts with carcinoid syndrome of 80+ months has to be compared with 8-12 months on chemotherapy (streptozotocin plus 5-FU). Treatment of endocr ine pancreatic tumors with alpha-IFN at doses of 5-6 MU 3-5 times per week achieved biochemical responses in 51 % of the patients and tumor responses in 12 %. The median duration of response was 20 months (rang e 2-96). Combining alpha-IFN with the somatostatin analogue octreotide in patients with malignant tumors resistant to octreotide alone got b iochemical responses in 77% with 18% complete biochemical remissions. No significant reduction of tumor size was noticed, but stabilization of the disease was obtained for a median of 15 months. Combination of streptozotocin, doxorubicin and alpha-IFN-2a did not present any advan tage over IFN-2a alone. The side effects of this combination were cons iderable. The adverse reactions to alpha-IFN therapy include 'flu-like ' symptoms, fatigue, weight loss, anemia, depression and liver dysfunc tion of various degrees and are dose dependent. Around 15-20% of the p atients might develop autoimmune reactions and patients on recombinant alpha-IFNs may develop neutralizing IFN antibodies, which might abrog ate the antitumor response. In summary, alpha-IFN exerts significant a ntitumor effects in neuroendocrine tumors; this has been registered in several countries. The side effects are manageable and mainly dose de pendent and it is important to titrate the dose individually in each p atient. Future studies will demonstrate the beneficial value of combin ing alpha-IFN with other biological agents such as somatostatin analog ues.