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Louis de Mestier, Clarisse Dromain, Gaspard d'Assignies, Jean-Yves Scoazec, Nathalie Lassau, Rachida Lebtahi, Hedia Brixi, Emmanuel Mitry, Rosine Guimbaud, Frédéric Courbon, Michèle d'Herbomez and Guillaume Cadiot

Well-differentiated neuroendocrine tumors (NETs) are a group of heterogeneous rare tumors. They are often slow-growing and patients can have very long survival, even at the metastatic stage. The evaluation of tumor progression and therapeutic responses is currently based on Response Evaluation Criteria In Solid Tumors v1.1 (RECIST) criteria. As for other malignancies, RECIST criteria are being reexamined for NETs in the era of targeted therapies because tumor response to targeted therapies is rarely associated with shrinkage, as opposed to prolonged progression-free survival. Therefore, size-based criteria no longer seem to be suitable to the assessment of NET progression and therapeutic responses, especially considering targeted therapies. New imaging criteria, combining morphological and functional techniques, have proven relevant for other malignancies treated with targeted therapies. To date, such studies have rarely been conducted on NETs. Moreover, optimizing the management of NET patients also requires considering clinical, biological, and pathological aspects of tumor evolution. Our objectives herein were to comprehensively review current knowledge on the assessment of tumor progression and early prediction of therapeutic responses and to broaden the outlook on well-differentiated NETs, in the era of targeted therapies.

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Laetitia Dahan, Frank Bonnetain, Philippe Rougier, Jean-Luc Raoul, Eric Gamelin, Pierre-Luc Etienne, Guillaume Cadiot, Emmanuel Mitry, Denis Smith, Frédérique Cvitkovic, Bruno Coudert, Floriane Ricard, Laurent Bedenne, Jean-François Seitz and for the Fédération Francophone de Cancérologie Digestive (FFCD) and the Digestive Tumors Group of the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC)

The aim of this randomized multicenter phase III trial was to compare chemotherapy and interferon (IFN) in patients with metastatic carcinoid tumors. Patients with documented progressive, unresectable, metastatic carcinoid tumors were randomized between 5-fluorouracil plus streptozotocin (day 1–5) and recombinant IFN-α-2a (3 MU×3 per week). Primary endpoint was progression-free survival (PFS). From February 1998 to June 2004, 64 patients were included. The two arms were well matched for median age, sex ratio, PS 0–1, previous chemotherapy, surgery, or radiotherapy. The median PFS for chemotherapy was 5.5 months versus 14.1 for IFN (hazard ratio=0.75 (0.41–1.36)). Overall survival (OS), tolerance, and effects on carcinoid symptoms were not significantly different. Despite a trend in favor of IFN, there was no difference in PFS and OS in advanced metastatic carcinoid tumors and therapeutic effect of both treatments was mild.