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

Abstract

BackgroundWell-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.MethodsTwenty-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.ResultsAssessment 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.ConclusionContinuous/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 registrationNCT00953394

Peptide receptor radionuclide therapy for neuroendocrine tumours: standardized and randomized, or personalized?

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Frequency and characterization of gastro–entero–pancreatic neuroendocrine tumor patients with high-grade of uptake at somatostatin receptor scintigraphy

“…By contrast, patients with tumors displaying high proliferative capacity could be considered as best candidates for chemotherapy (Brizzi et al 2009, Turner et al 2010. Our study confirms the results of previous more limited studies that have reported, in 48-88 patients, correlations between SRS uptake and different NEN characteristics, such as good performance status (Krenning et al 1994), presence of a functioning NEN (Taal et al 1996, Stokkel et al 2011, high level of CgA (Kalkner et al 1995, Asnacios et al 2008, Namwongprom et al 2008, Stokkel et al 2011, or low proliferative index (Adams et al 1998, Ezziddin et al 2006.…”

ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, Pancreatic, Bronchial Neuroendocrine Neoplasms (NEN) and NEN of Unknown Primary Site

“…Metronomic chemotherapy may be an option using temozolomide and/or capecitabine +/- SSA in G2 NET or in SSTR-negative NET, or capecitabine + bevacizumab after failure of other treatments (such as locoregional therapies, IFN-alpha or everolimus) [69,70,71,72]. Given the limited treatment options in bronchial carcinoids, temozolomide is a therapeutic option based on data from small studies [73,74].…”