The typical duration of treatment with somatostatin analogues is approximately 12 months because of the development of tachyphylaxis (reported less frequently with long-acting formulations) and/or disease progression.[15,16,17] In the management of carcinoid crises, intravenous somatostatin analogues are effective; crises are usually precipitated by anesthesia, surgical interventions, or radiologic interventions. Adverse effects of somatostatin analogue administration include:[19,20]
- Loose stools.
- Cardiac conduction abnormalities and arrhythmias.
- Endocrine disturbances (e.g., hypothyroidism, hypoglycemia, or, more commonly, hyperglycemia).
- Gastric atony (rarely).
Biliary sludge and cholelithiasis occur in as many as 50% of the patients, but few patients (1%–3%) develop acute symptoms requiring cholecystectomy.
The most researched interferon in the treatment of carcinoid disease is interferon-alpha (IFN-alpha); comparable to somatostatin analogues, the most pronounced effects of IFN-alpha are inhibition of disease progression and symptom relief, with approximately 75% of patients reporting the resolution of diarrhea or flushing. IFN-alpha, similar to other IFNs studied in the treatment of carcinoids (e.g., IFN-gamma and human leukocyte interferon), has substantial adverse effects, including alopecia, anorexia, fatigue, weight loss, fever, a flu-like syndrome, and myelosuppression; however, IFN-alpha may show greater antitumor activity than somatostatin analogues. Both single-agent and multiagent chemotherapeutics appear to have little role in the management of these essentially chemoresistant tumors; no protocol has shown objective tumor response rates greater than 15%.
Treatment of Hepatic Metastases
The management of hepatic metastases may include surgical resection; hepatic artery embolization; cryoablation and radiofrequency ablation (RFA); and orthotopic liver transplantation. In one large review of 120 carcinoid patients, a biochemical response rate of 96% and a 5-year survival rate of 61% were reported for patients whose hepatic metastases were resected surgically. The 5-year survival rate without surgical therapy is approximately 30%. For hepatic artery embolization, the most frequently used single agent is gelatin powder; and, in more than 60 patients with carcinoid tumors, the use of gelatin powder resulted in 34% and 42% of patients achieving biochemical and tumor-diminution responses, respectively.[23,24,25] Trials using transcatheter arterial occlusion with chemoembolization have also been performed, with the most thoroughly researched combination involving hepatic artery ligation with gelatin foam and doxorubicin (4 trials and 66 patients), resulting in biochemical responses in 71% of patients and tumor regression in approximately 50% of patients. However, the duration of response can be short lived after embolization, and embolization may be associated with adverse effects that range from transient symptoms (e.g., pain, nausea, fever, and fatigue), which occur in 30% to 70% of patients, to liver enzyme abnormalities, which occur in as many as 100% of patients (i.e., transaminitis and postembolization syndrome), to florid and potentially lethal carcinoid crisis with massive release of vasoactive substances.