Annals of Oncology Advance Access published online on June 23, 2006
Annals of Oncology, doi:10.1093/annonc/mdl144
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1 Department of Medicine, European Institute of Oncology, Milan
* To whom correspondence should be addressed. In most cases gastro-enteropancreatic neuroendocrine tumors grow slowly. Interferon-
Received March 26, 2006
Revised May 15, 2006
Accepted May 16, 2006
review
Interferon-
N. Fazio 1 *,
F. de Braud 1,
G. Delle Fave 2,
and
K. Öberg 3
and somatostatin analog in patients with gastroenteropancreatic neuroendocrine carcinoma: single agent or combination?
2 Department of Digestive and Liver Disease, ‘La Sapienza’ University, Rome, Italy
3 Department of Internal Medicine, Uppsala University, Uppsala, Sweden
N. Fazio, E-mail: nicola.fazio{at}ieo.it
Abstract 
and somatostatin analogs have shown symptomatic, biochemical, and, in a minority of cases, antiproliferative activity. Generally, they are proposed as single-agent therapy. However, based on in vitro and in vivo evidence, the combined use of these drugs was proposed in several non-randomized trials, indicating that there is an additive effect of the combination. Nevertheless, the three randomized trials published so far did not show a statistically significant survival benefit for the combination compared to the same agents alone, even though an advantage for the combination came out in all three studies. On the other hand, data from non-randomized trials would justify the sequential use of the two drugs or the combination after progression on single agent therapy. Therefore, at present the up-front combined use of interferon- and somatostatin analog is not justified, whereas it could be indicated after progression to single-agent therapy. Further larger, international, prospective, randomized, multicentric clinical trials studying homogeneous populations would be necessary to give a final answer, but the rarity and heterogeneity of this malignancy does not assure that it will be possible.
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