Standard treatments for patients with gastrointestinal (GI) carcinoid tumors include the following:
- Somatostatin analogues.
- Treatment of hepatic metastases.
- Management of carcinoid-related fibrosis.
- Symptomatic therapy.
Treatments being tested in clinical trials include the following:
- Molecular-targeted therapies.
- Therapies for symptomatic relief.
- Antifibrotic therapies.
The only potential curative therapy for GI carcinoids, which may be possible in as many as 20% of patients, is resection of the primary tumor and local lymph nodes.[2,3,4] Endoscopic surgery may be suitable for some tumors depending on the location, number, size, and degree of malignancy. Resection of nonhepatic tumor primaries is associated with increased median survival ranging from 69 to 139 months.[5,6] However, the extent of resection depends on the site of origin of a given tumor, the involvement of surrounding structures, and the extent of metastases.
The development of long-acting and depot formulations of somatostatin analogues has been important in the amelioration of symptoms of carcinoid syndrome. The result has been a substantial improvement in quality of life with relatively mild adverse effects.[1,7] The inhibitory effects of somatostatin on neurotransmission, motor and cognitive functions, smooth muscle contractility, glandular and exocrine secretions, intestinal motility, and absorption of nutrients and ions are mediated by cyclic adenosine monophosphate inhibition.[8,9] Experimentally, somatostatin has been shown to have a cytostatic effect on tumor cells. This effect involves hyperphosphorylation of the retinoblastoma gene product and G1 cell cycle arrest, in addition to somatostatin receptor (SSTR) subtype 3 [sst(3)]-mediated (and to a lesser extent, SSTR subtype [sst(2)]-mediated) apoptosis.[10,11,12] Somatostatin also appears to have some antiangiogenic properties. However, only a small number of patients treated with somatostatin analogue therapy experience partial tumor regression.[1,4]
Currently available somatostatin analogues display high affinity for sst(2) and SSTR subtype 5, low affinity for SSTR subtype 1 and SSTR subtype 4, and medium affinity for sst(3). (Refer to the Somatostatin Receptor Scintigraphy section in the General Information About Gastrointestinal Carcinoid Tumors section of this summary for more information.) Octreotide, a short-acting somatostatin analogue and the first biotherapeutic agent used in the management of carcinoid tumors, exhibits beneficial effects that are limited to symptom relief, with about 70% of patients experiencing resolution of diarrhea or flushing. [1,4]
In the treatment of carcinoids, lanreotide, a long-acting somatostatin analogue administered every 10 to 14 days, has an efficacy similar to that of octreotide and an agreeable formulation for patient use. The effects of lanreotide on symptom relief are comparable to those of octreotide, with 75% to 80% of patients reporting decreased diarrhea and flushing; however, there appears to be little improvement in tumor responses over shorter-acting octreotide. Depot formulations include long-acting repeatable (LAR) octreotide and a slow-release depot preparation of lanreotide. One study comparing subcutaneous short-acting octreotide with monthly LAR octreotide reported an increased median survival from the time of metastatic disease diagnosis (143 months vs. 229 months in favor of the LAR form), representing a 66% lower risk for death among patients treated with the LAR formulation. A randomized controlled study in metastatic midgut neuroendocrine tumors showed improved time to tumor progression with monthly LAR octreotide compared to placebo. (Refer to the Jejunal and Ileal carcinoids section in the Treatment Option Overview section of this summary.)