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Table 1 A summary of currently used therapy modalities (systemic and liver loco-regional) for advanced GEP NETs, indicating reference studies for each one, and frequent side effects

From: Current treatment strategies for patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs)

Drug Study Population (n) Design Primary end-point Main Outcome Major side effects
Octreotide LAR Rinke et al. 2009 [10], PROMID study Intestinal NETs F/NF (85) Randomized phase III PFS 14.3 months vs 6 months with placebo Diarrhea, flatulence, cholelithiasis
Lanreotide autogel Caplin et al. 2014 [11], CLARINET study NF Intestinal/ Pancreatic NETs (204) Randomized phase III PFS Median not reached vs 18 months with placebo Diarrhea, flatulence, cholelithiasis, hyperglycemia
Interferon Oberg et al. 2012 [15] GEP NETs, carcinoid syndrome Review Clinical and biochemical response, tumor effect Symptoms relief up to 70%, biochemical response 50–60%, SD up to 70% Flu-like symptoms, chronic fatigue, liver toxicity, bone marrow suppression, depression, autoimmune-related conditions
Everolimus Yao et al., 2008 [21], RADIANT-1 study PNET (160) Single-arm (± sandostatin) phase II Response rate 8.7% objective response rate; 84.7% stable disease  
  Pavel et al., 2011 [23], RADIANT-2 study Intestinal NETs (420) Randomized phase III PFS 16.4 months vs 11.3 months with placebo Stomatitis, rash, fatigue, diarrhea, nausea, infections, fever, cytopenia, edema, hyperglycemia, dyspnea, pneumonitis
  Yao et al., 2011 [23], RADIANT-3 study PNETs (410) Randomized phase III PFS 11 months vs 4.6 months with placebo
  Yao et al. 2016 [24], RADIANT-4 study Lung/Intestinal NETs (302) Randomized phase III PFS 11 months vs 3.9 months with placebo
Sunitinib Raymond et al. 2011 Pancreatic NETs (171) Randomized phase III PFS 11.4 months vs 5.5 months with placebo Diarrhea, nausea, asthenia, vomiting, fatigue, HTN, neutropenia, stomatitis, palmar-plantar erythrodysesthesia
Telotristat ethyl Pavel et al. 2015 [16], TELESTAR study Carcinoid syndrome (135) Randomized phase III Reduction in daily bowel movements Mean reduction of 1.7–2.1 BM/day (dose dependent) vs 0.9 with placebo Nausea, abdominal pain, vomiting, fatigue, infections, increased LFTs
PRRT Strosberg et al. 2017 [33], NETTER-1 trial Intestinal NETs (229) Randomized phase III PFS PFS at 20 months 65.2% vs 10.8% with SSA alone Nausea, vomiting, renal impairment, marrow toxicity
STZ-5FU Dilz et al. 2015 [40]; Clewemar et al. 2016 [41] pNETs (96) pNETs (133) Retrospective PFS 19.4 months 23 months Nausea, fatigue, kidney toxicity, bone marrow suppression
CAPTEM Strosberg et al. 2011 [45]; Fine et al. 2013 [46] pNETs (30) GEP NETs (18) Retrospective PFS 18 months 14 months Fatigue, nausea, myelosuppression, palmar-plantar erythrodysesthesia
TACE Grozinsky-Glasberg et al. 2018 [54] NETs (57) Retrospective PFS 14 months Fever, leukocytosis, abdominal pain, nausea, elevated liver enzymes (post embolization syndrome), carcinoid crisis, liver failure, cholecystitis, liver abscess
SIRT Kennedy et al. [55] NETs (158) Retrospective Imaging response SD 22.7%, PR 60.5%, CR 2.7%, PD 4.9% Fatigue, nausea, pain, ascites,
  1. F functioning, NF non-functioning, PFS progression free survival, PRRT peptide receptor radionuclide therapy, STZ-5FU streptozotocin + 5-fluorouracil, CAPTEM capecitabin + temozoomide, TACE trans-arterial chemoembolization, SIRT selective interval radiation therapy, HTN hypertension, LFT liver function tests