Chemotherapy in the treatment of neuroendocrine malignant tumors

The efficacy of chemotherapy in digestive neuroendocrine tumors (NET) depends on primary site and histological differentiation. Many reports have suggested a superior activity of chemotherapy for pancreatic NET than for metastatic carcinoid tumors with response rates ranging from 40 to 60% compared to 20%. The standard chemotherapy for pancreatic NET is a combination of adriamycin and streptozocin and to a lesser extent a combination of 5FU and streptozocin. In contrast, there is no clear standard chemotherapy for carcinoid tumors and if most oncologists use a combination of 5FU and streptozocin in the case of advanced, progressive and nonresectable carcinoid tumors, the results are mostly poor and the benefit seldom counterbalances its toxicity. In these carcinoid tumors the combination of hepatic artery ischemia alternating with chemotherapy has given impressive results in one study, which, however, have never been confirmed. Tumor cell differentiation is a major prognostic factor and some reports have suggested a higher chemosensitivity for undifferentiated or poorly differentiated NET with tumor response rates ranging from 41 to 69% when a VP16-CDDP combination is used. This chemosensitivity is, unfortunately, as in small cell lung carcinomas, of short duration. Related to this special problem and the number of other active treatments in NET, the place of chemotherapy always has to be discussed in a multidisciplinary fashion. Surgical excision, chemoembolization, interferons and somatostatin analogues have to be emphasized and eventually combined with chemotherapy, especially in slowly growing tumors. New active chemotherapy regimens have to be tested clearly in this orphan group of tumors which does not hold much interest to the pharmaceutical companies.