Chemotherapy for advanced non-pancreatic well-differentiated neuroendocrine tumours of the gastrointestinal tract, a systematic review and meta-analysis: a lost cause?

Publication date: Available online 25 January 2016
Source:Cancer Treatment Reviews
Author(s): Angela Lamarca, Emma Elliott, Jorge Barriuso, Alison Backen, Mairéad G. McNamara, Richard Hubner, Juan W. Valle
BackgroundChemotherapy is well-established in the treatment of patients with well-differentiated neuroendocrine tumours (NETs) arising from the pancreas (pNETs); however, its role in patients with gastrointestinal non-pancreatic NETs (non-pNETs) is uncertain. This systematic review assesses the evidence for the role of chemotherapy in well-differentiated non-pNET patients.MethodsEligible studies (identified using MEDLINE) were those reporting response and/or survival data for patients with well-differentiated non-pNETs receiving systemic chemotherapy. The primary end-point was overall-response (OR) rate; secondary end-points were progression-free survival (PFS), overall survival (OS), disease-stabilisation (DS) and disease-control (DC) rates.ResultsOf 6,434 studies screened, 20 were eligible: one randomised phase III trial, 2 randomised phase II studies, 10 single-arm phase II trials and 7 retrospective analyses including a total of 264 patients (median of 11 patients per study, range 6-49); and employing multiple chemotherapy schedules. The mean "median PFS" and "median OS" were 16.9 months (95%-confidence interval (CI) 3.8-30.04) and 32.2 months (95%-CI 10.4-54.2), respectively. The non-weighted mean OR, DS and DC rates were 11.5% (95%-CI 5.8-17.2), 56.5% (95%-CI 38.1-74.9) and 70.7% (95%-CI 54.9-86.5), respectively. In studies including both pNETs and non-pNET patients, meta-analysis showed a lower OR-rate in the non-pNET patients when compared to pNETs [odds ratio (OR) 0.35 (95% CI 0.18-0.66); however significance was lost when high-risk bias studies were excluded in a sensitivity analysis [OR 0.45 (95% CI 0.19-1.07); p-value 0.07].ConclusionStudies were of evidence level-C with heterogeneous populations and treatments; and small patient numbers. Well-designed, prospective studies are needed to adequately evaluate the role of chemotherapy in this setting.

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