There is little experience with the use of adjuvant chemotherapy following surgical resection. The small number of patients treated, the relatively indolent nature of these tumors, and the short follow-up times are insufficient to recommend adjuvant chemotherapy outside of clinical trials. However, it may be appropriate to consider adjuvant chemotherapy in selected patients felt to be at high risk of subsequent recurrence, understanding that there is little data to show benefit with this approach.

The activity of chemotherapy in patients with metastatic gastrinomas is difficult to determine since most published series have studied chemotherapy for all histologic types of pancreatic endocrine tumors grouped together. In addition, the growth rate of metastatic gastrinoma varies markedly [78], further complicating assessment of response to therapy. Streptozotocin appears to be the most active single agent in patients with metastatic gastrinoma, with objective response rates reported in up to 50% of patients [79-83]. There is no evidence that the addition of 5-FU with or without doxorubicin improves the outcome compared to streptozotocin alone [81, 84]. Differences in the doses used, the schedules of administration, and the criteria used to assess tumor responses, make firm management recommendations difficult. Octreotide, either alone or combined with interferon, appears to have a role in management of these patients. The development of a long-acting somatostatin analogue (lanreotide) has greatly facilitated management, and is effective in reducing symptoms in 38-64% of patients [85]. A known side effect is the development of gallstones. In a small study of 21 pancreatic neuroendocrine tumor patients from Marburg, Germany, 14 patients responded to combined octreotide and alpha-interferon, primarily with disease stabilization [86]. Of note, 16 of the patients failed to respond to octreotide alone.

Overall response rates to systemic therapy remain disappointing. A multi-center clinical trial randomized 80 patients with metastatic neuroendocrine tumors to lanreotide, interferon alpha, or both. There was no significant difference between the treatment arms, with partial remission rates of 4.0 to 7.1%, disease stabilization rates from 28-17.9% and progression of disease from 56-50% [87]. Another smaller study of 15 patients with progressive hepatic metastases showed slightly better results with long-acting octreotide, with partial response rates of 6% (one patient), and stabilization in 47% [88].

A study of 16 patients with disseminated neuroendocrine tumors examined the efficacy of high activity (111) In-pentetreotide. There was minimal toxicity, and at six months there were two complete responses, and three partial responses. Disease progression was 30% at six months, and 69% at eighteen months [89].