Management of carcinoid syndrome: a systematic review and meta-analysis

Abstract

Carcinoid syndrome (CS) is a debilitating disease caused by functional neuroendocrine tumors. Several treatment options are available to alleviate the hormonal symptoms, but their relative efficacy is unknown. Online databases were searched for publications on the treatment of CS symptoms. Independent reviewers assessed relevant publications for study quality and outcome. Meta-analysis of the outcomes of the intervention on CS-related symptoms was stratified by the type of treatment. We found 3682 therapeutic interventions on CS-specific outcomes were collected from 93 studies. Overall, the study qualities were poor with only six randomized controlled clinical trials. The somatostatin analogs octreotide and lanreotide induced symptomatic improvement in 65–72% and biochemical response in 45–46% of patients. An increase in dose or frequency or interclass switch led to a reduction of flushes and/or diarrhea in 72–84% of cases. Retrospective, institutional series showed that liver-directed therapy can improve symptoms in 82% of CS patients with a liver-dominant disease. The serotonin synthesis inhibitor telotristat ethyl reduced bowel movements in 40% of patients with diarrhea refractory to somatostatin analogs. Interferon-alpha controlled CS symptoms in 45–63% of cases. Favorable response has been noted after radionuclide therapy in subgroup analyses of studies not specifically involving CS patients. Chemotherapy and everolimus did not induce a significant response in the CS. We conclude that several treatment lines can be offered to patients suffering from the carcinoid syndrome. Initiation of randomized controlled trials with a primary outcome on carcinoid syndrome symptoms is strongly recommended.

Update on Pathophysiology, Treatment, and Complications of Carcinoid Syndrome

“…Limited data exist concerning the role of PRRT in patients with refractory carcinoid syndrome without evidence of radiologically progressive disease. e aforementioned meta-analysis shows 64-74% of symptom improvement based on 4 small-phase II studies [61]. Two small studies with 11 and 14 NEN patients with carcinoid syndrome report a good effect of ondansetron in reducing diarrhoea [70,71].…”

“…A recent meta-analysis shows symptom improvement in 65-72% of patients and biochemical response in around 45% of patients on somatostatin analogues. Increasing the dose or frequency or switching the drug type led to a reduction of symptoms in 72-84% of patients [61]. e CLARINET study randomized the GEP-NEN patients and patients with unknown primary tumour between Lanreotide autogel 120 mg and placebo and showed significantly prolonged the progression-free survival in the Lanreotide group (median not reached versus 18 months for the placebo group) [62].…”

Carcinoid Syndrome

“…Carcinoid crisis can occur spontaneously, but it is commonly precipitated by stressful procedures such as anesthesia, surgery, and tumor manipulation or following tumor cytoreductive procedures and radiologic interventions due to tumor lysis. Although prophylactic measures are available, carcinoid crisis is not entirely preventable; thus, it requires prompt recognition and aggressive treatment (Ito et al 2018;Loughrey et al 2018;Hofland et al 2019).…”

“…These liverdirected therapies are usually highly effective and well-tolerated, with low mortality rates. A postembolization syndrome characterized by fever and fatigue may occur in some patients; other less common complications include bile duct injury, liver fibrosis, radiation gastritis, bowel or liver ischemia with liver abscess, and hepatorenal failure or sepsis (Rubin de Celis Ferrari et al 2018;Ito et al 2018;Loughrey et al 2018;Hofland et al 2019).…”

Atypical Carcinoid Syndrome

“…Carcinoid crisis can occur spontaneously, but it is commonly precipitated by stressful procedures such as anesthesia, surgery, and tumor manipulation or following tumor cytoreductive procedures and radiologic interventions due to tumor lysis. Although prophylactic measures are available, carcinoid crisis is not entirely preventable; thus, it requires prompt recognition and aggressive treatment (Tomassetti et al 2001;Hofland et al 2019).…”