Treatment Option Overview
The four radionuclide conjugates most commonly used in the treatment of carcinoid disease are 131I-MIBG (iodine-131-meta-iodobenzylguanidine), indium-111, yttrium-90, and lutetium-177, with the latter three bound to a variety of somatostatin analogues. However, the median tumor response rate for the patients treated with 131I-MIBG is less than 5%, although the modality appears somewhat more effective in achieving biochemical stability (~50%) or tumor stability (~70%). Although 111In-labeled somatostatin analogues are the most commonly studied radiopeptides to date, largely reflecting their availability, and with therapeutic benefits similar to 131I-MIBG, the most promising advance in radiopeptide therapeutics has been the development of 177Lu-octreotate, which emits both beta and gamma radiation. In the largest patient series treated to date with lutetium-labeled somatostatin analogues (n = 131; 65 with GI carcinoids), remission rates were correlated positively with high pretherapy octreotide scintigraphy uptake and limited hepatic tumor load. In patients with extensive liver involvement, median time to progression was shorter (26 months) compared to patients who had either stable disease or tumor regression (>36 months).
Management of Carcinoid-Related Fibrosis
Bowel obstruction secondary to peritoneal fibrosis is the most common presenting symptom of small intestinal carcinoids. Heart failure secondary to right-sided valvular fibrosis represents a serious extraintestinal manifestation of carcinoid fibrosis and occurs in 20% to 70% of patients with metastatic disease; it accounts for as much as 50% of carcinoid mortality.[28,29] Currently, there is no effective pharmacologic therapy for either clinical problem. In the instance of bowel obstruction, surgical lysis of the adhesions often is technically demanding because of the cocoon-like effects of extensive fibrosis stimulated by the various tumor-derived growth factors. Valvular replacement usually is required to manage carcinoid heart disease.
In addition to the use of long-acting depot formulations of somatostatin analogues as the principal agents in the amelioration of carcinoid symptoms, the nonspecific supportive care of patients includes:
- Advising them to avoid factors that induce flushing or bronchospastic episodes including the following:
- Diarrhea may be treated with conventional antidiarrheal agents such as loperamide or diphenoxylate; more pronounced diarrhea may be treated with the 5-HT receptor subtype 2 antagonist cyproheptadine, which is effective in as many as 50% of patients and may also help alleviate anorexia or cachexia in patients with a malignant carcinoid syndrome.
- Histamine 1 receptor blockade with fexofenadine, loratadine, terfenadine, or diphenhydramine may be of benefit in treating skin rashes, particularly in histamine-secreting gastric carcinoid tumors.
- Bronchospasm can be managed with theophylline or beta-2 adrenergic receptor agonists such as albuterol.