Treatment Options for Carcinoid Tumors

Management of Symptoms of Carcinoid Tumors

Management of symptoms related to carcinoid tumor, most notably carcinoid syndrome related to tumors of the GI tract and lung, may be achieved by using two different types of agents, biological agents and chemotherapy. The objective is to increase the quality of life by reducing the symptoms such as flushing, diarrhea, etc. The agents work by decreasing hormone levels by destroying cancer cells.

Symptoms related to lung carcinoid tumors may differ slightly in that they are caused by more histamine production and these are controlled through the use of histamine receptor antagonists.

Biologic Agents

Biologic agents have been shown to significantly improve quality of life and survival in patients with midgut carcinoids. Estimates of their effectiveness in improving clinical symptoms range from 50-70% and approximately 40-60% of patients experience reduction of hormone levels in the blood. Biologic agents are not curative although they have been shown in some cases to actually reduce tumor size and in up to 80% of patients. The disease is stabilized over a period ranging from 2-5 years.

Examples of biological agents that may be used in the management of patients with carcinoid tumors include:

• Somatostatin Analogs
• Interferon-alpha

Somatostatin Analogs

The initial management of symptoms should be the control of excessive hormonal secretion. A long acting synthetic analog of somatostatin (octreotide; Sandostatin LAR) is currently approved for the treatment of Carcinoid Syndrome.

Side effects of somatostatin analogs are not common but may include:

• Gallstone formation
• Nausea
• Diarrhea
• Abdominal pain
• Malabsorption of fats

Interferon-alpha

Interferon-alpha is a biological agent that is used to raise the level of the natural immune activity of the cells. It is often used in combination with either somatostatin analogs or with chemotherapy for greatest efficacy. Interferon-alpha exerts an antitumor activity which slows various processes of the tumor such as proliferation of the tumor cells and angiogenesis (formation of a rich blood supply for the tumor). It appears to be most effective with midgut tumors, even when given alone. Tumor regression is estimated to occur in up to 15% of patients. Combining treatment with both somatostatin analogues and interferon alpha can lead to measurable decreases in metastatic tumor cells in up to one-third of patients.

Side effects of interferon-alpha therapy may include:

• Flu-like symptoms (usually temporary)
• Fatigue
• Mild depression

More recently, a newer formulation of interferon-alpha has become available called pegylated interferon. Pegylated interferon is a slightly different preparation of interferon-alpha that is associated with fewer side effects and may have a stronger antitumor effect.

Chemotherapy

Chemotherapy is not particularly effective against carcinoid tumors and is used mostly in cases where the metastatic activity is high as measured by the Ki-67 antigen (a protein expressed by some cancer cells that is a "marker" of cell proliferation). Chemotherapy appears to be most effective for bronchial and thymic carcinoid tumors. Response to chemotherapy is of short duration and indications of prolonged survival are not clear. Also, some people (estimates range between 20% to 75%) react strongly to the side effects of chemotherapy and their quality of life is compromised. In general, chemotherapy is reserved for more aggressive tumors.

Chemotherapeutic drugs used for the treatment of carcinoid tumors include:

• 5-fluorouracl (5-FU)
• Streptozotocin
• Adriamycin

Biologic therapy and chemotherapy may be used alone or in combination.

Under certain circumstances, various procedures may be utilized to debulk (shrink) the size of the tumor. These debulking procedures may include surgery, arterial embolization, cryosurgery, or radiofrequency ablation. Debulking the tumor also reduces the number of cells expressing the substances or hormones related to the symptoms.

Depending upon the specific clinical complications of the disease, additional surgery may be required to relieve complications such bowel obstruction or, if the heart valves are damaged, valve replacement surgery may be necessary.