Research article

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

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

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

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

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

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

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

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

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

author email corresponding author email

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

Published:	3 November 2009

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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

NCT00953394