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Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

Maria P Brizzi1, Alfredo Berruti1, Anna Ferrero1, Enrica Milanesi3, Marco Volante2, Federico Castiglione4, Nadia Birocco3, Sebastiano Bombaci5, Davide Perroni6, Benedetta Ferretti7, Oscar Alabiso8, Libero Ciuffreda3, Oscar Bertetto3, Mauro Papotti2 and Luigi Dogliotti1*

Author Affiliations

1 Oncologia Medica, Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Azienda Ospedaliera San Luigi, Regione Gonzole, 10, 10043 Orbassano (TO), Italy

2 Anatomia Patologica, Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Azienda Ospedaliera San Luigi, Regione Gonzole, 10, 10043 Orbassano (TO), Italy

3 Centro Oncologico Ematologico Subalpino, Azienda Ospedaliera Molinette, Corso Bramante, 88, 10126 Torino, Italy

4 Oncologia Medica, Ospedale San Lazzaro, Via Pierino Belli, 26, 12051 Alba (CN), Italy

5 Oncologia Medica, Ospedale di Ivrea, P. Della Credenza, 2, 10015 Ivrea (TO), Italy

6 Oncologia Medica, Ospedale Civile di Saluzzo, Via Spielberg, 58, 12037 Saluzzo (CN), Italy

7 Oncologia Medica, Ospedale "B. Eustacchio", Via Del Glorioso, 8, 62027 San Severino Marche (MC), Italy

8 Oncologia Medica, Azienda Ospedaliera "Maggiore della Carità", Corso Mazzini, 18, 28100 Novara, Italy

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BMC Cancer 2009, 9:388  doi:10.1186/1471-2407-9-388

Published: 3 November 2009



Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion plus long-acting release (LAR) octreotide in patients with neuroendocrine carcinoma.


Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m2 daily) plus LAR octreotide (20 mg monthly). Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival.


Assessment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria showed partial response in 7 (24.1%), stable disease in 20 (69.0%), and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A) response was observed in 12/25 assessable patients (48.0%); symptom relief was obtained in 9/15 symptomatic patients (60.0%). There was non significant decrease in circulating vascular epithelial growth factor (VEGF) over time. Median time to progression was 22.6 months (range, 2.7-68.5); median overall survival was not reached yet. Toxicity was mild and manageable.


Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future.

Trial registration