Table 1.
Management of refractory carcinoid syndrome: available studies.
| Reference | Patients | Definition of RCSy | Intervention | Study design | Results (symptomatic response) | Drawbacks |
|---|---|---|---|---|---|---|
| Strosberg et al. [2014] |
n = 239; n with RCSy = 148 |
CSy symtoms uncontrolled while on octreotide LAR 10–30 mg | Octreotide LAR dose escalation to 40 or 60 mg every 28 days | Multicenter retrospective | 81% improved flushing and 79% improved diarrhea | Duration and magnitude of symptom control not reported |
| Al-Efraij et al. [2015] |
n = 37; n with RCSy = 27 |
Patients that remain symptomatic in spite of standard doses of octreotide LAR 30 mg | Octreotide LAR dose escalation to 40 or 60 mg every 28 days | Retrospective | 91% improved flushing and 62% improved diarrhea; reduction of 5-HIAA levels in 23% | Duration and magnitude of symptom control not reported; variable intervals for measuring tumor markers |
| Ferolla et al. [2012] |
n = 28; n with RCSy = 19 |
CSy symtomns while on octreotide LAR 30 mg every 28 days | Octreotide LAR 30 mg every 21 days | Phase II | Complete and partial control of symptoms in 30% and 70% of cases, respectively. | Small sample, duration of symptom control not reported |
| Chadha et al. [2009] |
n = 54; n with RCSy = 20 |
Objective symptom progression or development of new CSy symptoms while on octreotide LAR 20−30 mg |
Octreotide LAR 40– 60 mg every 28 days | Retrospective | 45% of cases presented symptoms improvement | High dose of SSA was not the same for all patients; duration and magnitude of response not reported |
| Ricci et al. [2000] |
n = 15; n with RCSy = 10 |
Any CSy symptom after treatment with lanreotide 30 mg every 14 days | Octreotide LAR 20 mg every 28 days | Phase II | The overall symptomatic response rate was 82%. The median duration of response for diarrhea, abdominal pain, or both was 6.5 months (range 3−12+ months). | Small sample, severity of symptoms not reported |
| Pavel et al. [2006] |
n = 17; n with RCSy = 10 |
CSy symptoms while on octreotide LAR 30 mg every 28 days | Pegylated interferon | Phase II | 70% symptom improvement | Small sample, uncontrolled |
| Taal et al. [1996] |
n total = 30; n with CSy = 20 |
Uncontrolled CSy by conventional treatment | I-131MIBG | Phase II | Symptomatic relief in 60% of patients with CSy (14/20), with a median duration of 8 months. | Mixed patients with RCSy and treatment naïve, small sample, magnitude of response not reported |
| Pathirana et al. [2001] |
n = 12; n with RCSy = 5 |
Uncontrolled CSy by octreotide LAR 30 mg | I-131MIBG | Retrospective | 80% (4/5) of patients with RCSy had some symptomatic response | Small sample, magnitude of response not reported |
| Bainbridge et al. [2015] |
n total = 15; n with RCSy = 10 |
Worsening in symptoms despite SSA labeled dose | Everolimus added to SSA | Retrospective | 70% had improvement in symptoms | Small sample, magnitude of response not reported |
| Kvols et al. [2012] | n = 45 | Diarrhea/flushing were inadequately controlled by octreotide LAR | Pasireotide 600-900 μg SC BID | Phase II | Controlled diarrhea and flushing in 27% | Duration control not reported |
| Wolin et al. [2015] | n = 110 | Daily mean of at least four BMs or flushing episodes of 14 or more for 2 weeks | Pasireotide LAR 60 mg or octreotide LAR 40 mg | Phase III | Symptom control in 20.9% (Pasireotide) versus 26.7% (octreotide), p = 0.53 | Interim analysis results (stopped for futility) |
| Kulke et al. [2014] | n = 23 | ⩾4 BMs/day while on stable-dose octreotide LAR (30 mg every 28 days until 60 mg every 21 days) for at least 3 months |
Placebo (n = 5) versus telotristat etiprate (n = 18) with dosage escalated from 150 mg TID to 500 mg TID. | Randomized phase II |
Five (28%) of 18 patients treated with telotristat etiprate and no patients treated with placebo achieved a clinical response (⩾30% reduction from baseline in the daily mean number of BMs/week for 2 or more of the 4 weeks on trial) | Small sample |
| Pavel et al. [2015] | n = 15 | At least four BMs per day | Telotristat etiprate with dosage escalated from 150 mg TID to 500 mg TID. | Phase II | All patients experienced reductions in BMs per day (mean decrease, 43.5%); number of flushing episodes presented a reduction of 27%. | Small sample, uncontrolled |
| Kulke et al. [2015] | n = 135 | At least four BMs per day | Telotristat etiprate 250 mg or 500 mg orally TID versus placebo | Phase III | 35% and 29% patients reduced the mean daily frequency of BM with telotristat 500 and 250 mg, respectively, versus 17% on placebo | Quality-of-life data not reported (unpublished trial) |
MIBG, meta-iodobenzylguanidine; RCSy, refractory carcinoid syndrome; CSy, carcinoid syndrome; SSA, somatostatin analog; 5-HIAA, 5-hydroxiindolacetic acid; SC, subcutaneous; BID, twice daily; TID, three times a day; BM, bowel movements.