Gastrointestinal neuroendocrine tumors treated with high dose octreotide-LAR: A systematic literature review

Table 1 Description of included studies

Ref. (OCEBM)	Country, timeframe	Study design	Study subjects	Doses of SLAR administered (number of patients or number of doses)	Reasons for high dose SLAR2	Relevant outcomes reported
Strosberg et al[2] 2013 (5)	United States	Modified delphi process	404 patient scenarios of patients with unresectable metastatic well-differentiated carcinoid tumors	Subset of patient scenarios treated with SLAR (frequency: every 2 wk, 3 wk, 4 wk; dosing 30 mg, 40 mg, 60 mg, 90 mg, 120 mg)	NA/NR	Expert clinical opinion
Colao et al[8] 2010 (5)	Italy	Literature review	Pituitary tumors and NETs	NA/NR	NA/NR	Expert clinical opinion
Oberg et al[9] 2004 (5)	Europe, United States	Literature review	Relating to pts. with GEPNETs	NA/NR	NA/NR	Expert clinical opinion
Yao et al[10] 2008 (5)	United States	Letter to editor	Relating to pts. with NETs	NA/NR	NA/NR	Expert clinical opinion
Anthony et al[11] 2011 (3b)	United States, 2000-2006	Retrospective multicenter medical chart review	392 pts. with functioning NETs (with or without CS), treated with SLAR ≥ 4 mo	10 mg (22 doses), 20 mg (224), 30 mg (316), 40 mg (78), 50 mg (16), 60 mg (42)	Lack of efficacy	Efficacy, safety
Chadha et al[12] 2009 (2b)	United States, 2002-2007	Retrospective single-center medical chart review	54 pts. with GEPNETs treated with SLAR 20-30 mg	Median high dose of SLAR 40 mg, ranging 40-90 mg/mo (30 pts.)	Control of symptoms, treatment of tumor	Efficacy, safety, Expert clinical opinion
Costa et al[13] 20061 (4)	2005	Retrospective case series	9 pts. with progressive metastatic NETs treated with SLAR 20 mg/mo	20 mg/mo (9 pts.); 30 mg/mo, 40 mg/mo (3 pts.)	Treatment of tumor	Efficacy, Expert clinical opinion
Ferolla et al[14] 2012 (2b)	Italy	Multicenter open-label non-randomized prospective clinical trial	28 pts. with well-differentiated NETs, progressing at standard dose SLAR ≥ 6 mo	30 mg/28 d initially for 6-32 mo (28 pts.); 30 mg/21 d (28 pts.) for 4-48 mo	Control of symptoms, treatment of tumor, other	Efficacy, safety
Koumarianou et al[15] 20101(4)	2008-2009	Retrospective case series	13 pts. with pretreated progressive metastatic GEPNETs	30 mg/3 wk (12 pts.)	Treatment of tumor	Efficacy, safety
Markovich et al[16] 20121 (4)		Retrospective clinical trial	31 pts. with pretreated progressing disseminated NETs	20 mg/mo initially (29 pts.); 30 mg/mo (18); 40 mg/mo (13) long acting octreotide	Control of symptoms, treatment of tumor, other	Efficacy, safety
Valle et al[17] 20011 (4)		Retrospective single-center case series	8 pts. with metastatic carcinoid syndrome	Initially 20 mg/mo (5 pts), 15 mg/mo, 60/mo, 20/2 wk (all 1); escalated to 20 mg/3 wk, 30 mg/3 wk, 50 mg/4 wk, 120 mg/4 wk (4 pts.)	Control of symptoms	Efficacy, safety
Weber et al[18] 20121 (4)	United States, 2000-2010	Retrospective single-center medical chart review	337 pts. with metastatic small-bowel carcinoid tumors, treated with SLAR	27% (99 pts.) with increased high dose; common max doses were 40 mg/4 wk (37 pts.), 60 mg/mo (34), 30 mg/3 wk (17)	Control of symptoms, tumor progression, other	Efficacy
Wolin et al[19] 20131 (2b)		Multicenter randomized phase III clinical trial	110 pts. with unresponsive NET symptoms to standard dose SLAR	40 mg/28 d (57 pts.)	Control of symptoms	Efficacy, safety
Woltering et al[20] 2006 (3)	United States	Non-randomized prospective clinical trial	40 pts. with carcinoid syndrome on stable doses of SLAR for ≥ 3 mo	20 mg (8 pts.), 30 mg (19), 60 mg (13) SLAR/mo	Control of symptoms	Efficacy
Ludlam et al[21] 2011 (3a)	1965-2010	Systematic literature review	Relating to pts. with NETs	NA/NR	Control of symptoms	Safety
Strosberg et al[22] 20131 (2b)	United States, 2004-2010	Retrospective multicenter medical chart review	271 pts. with carcinoid and pancreatic NETs, treated with octreotide-LAR	40% (n = 82) of carcinoid pts had high dose: common max doses of 40 mg/mo (39%), 40 mg/3 wk (18%), 30 mg/2 wk (17%); and 23% (15) of pNET pts: 40 mg/mo (33%), 30 mg/2 wk (27%), 60 mg/mo (27%)	Control of symptoms, treatment of tumor, other	Expert clinical opinion
Xu et al[23] 20121 (3b)	United States, 1999-2007	Retrospective analysis of SEER-Medicare claims	355 pts. with NETs	26 pts. (7.3%) with ≤ 10 mg initially, of which 3.9% increased to > 40 mg; 91 (25.6%) with 11-20 mg initially, 5.5% increased to 31-40 mg and 4.4% to > 40 mg; 147 (41.4%) with 21-30 mg initially, 11.6% increased to 31-40 mg and 10.9% to > 40 mg; 65 (18.3%) with 31-40 mg initially, 86.2% increased to 31-40 mg and 13.9% to > 40 mg; 26 (7.3%) with > 40 mg initially, 100% increased to > 40 mg; 134 pts. (37.7%) escalated to > 30 mg/mo during 1st year of therapy	NA/NR	Expert clinical opinion

¹Conference abstract;

²Control of symptoms (flushing, diarrhea, and etc.); treatment of tumor (tumor progression); other (biochemical markers). NA/NR: Not applicable/not reported; OCEBM: Oxford’s Centre for Evidence-Based Medicine Levels Of Evidence; CS: Carcinoid syndrome; NETs: Neuroendocrine tumors; GEPNETs: Gastroenteropancreatic neuroendocrine tumors; SLAR: Octreotide long-acting repeatable; pts.: Patients.