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
Highlights
Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties
The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future
Study population Eligibility criteria included histological diagnosis of welldifferentiated neuroendocrine carcinoma according to the World Health Organization (WHO) classification [1], locally advanced or metastatic disease not amenable to surgery with radical intent, at least one measurable target lesion, radiological documentation of progressive disease, somatostatin receptor scintigraphy, Eastern Cooperative Oncology Group (ECOG) performance status grade ≤ 2, life expectancy ≥ 12 weeks, adequate bone marrow reserve (WBC count ≥ 3.5 × 109/L, platelets ≥ 100 × 109/L, hemoglobin ≥ 10 g/dL), adequate hepatic and renal function
Summary
Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. Somatostatin analogues effectively reduce hormonal hypersecretion, but tumor shrinkage is only rarely seen (0%-6% of patients) [5,6]. Because of their low proliferative activity, conventional chemotherapy for these tumors is not recommended [79]. Since welldifferentiated neuroendocrine carcinomas are highly vascular [14,15], there is a rationale for testing metronomic chemotherapy in this clinical setting [16]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
