Carcinoid Syndrome & VIPomas

Targeted Treatments

Targeted treatments for carcinoid syndrome address the underlying causes of the symptoms. Such treatments include:

• Surgical Debulking
• Hepatic Artery Embolization, Chemoembolization, or Ligation
• Medical Therapy
  • Octreotide Acetate
  • Interferon
  • Chemotherapy
• Radiotherapy

Surgical Debulking

For patients with carcinoid syndrome, surgical debulking of tumors can decrease the amount of hormones being produced by tumor cells. For some patients, this may provide some relief of symptoms. However, since surgeons are unable to remove all metastatic tumor presence, signs and symptoms of carcinoid syndrome may remain, or may return as the remaining tumor grows. Cryosurgery may sometimes be used to destroy carcinoid tumor cells in the liver when it is not possible to remove them surgically.

Surgery can also be used to relieve intestinal obstructions caused by tumors, which may relieve abdominal pain, bleeding, or other symptoms. Some patients with cardiac disease may have surgery for valve replacement.

Hepatic Artery Embolization, Chemoembolization, or Ligation

Another means of debulking tumor presence in the liver is to cut off the supply of blood and oxygen required for tumor growth. The rationale behind this approach is that the portal vein provides 75% to 80% of the blood supply to normal liver cells, while the hepatic artery only provides 20% to 25% of the normal blood supply (1). In contrast, the hypervascularity of hepatic neoplasms results in their deriving almost all of their blood supply from the hepatic artery. Thus, occluding a hepatic artery will cause tumor necrosis while preserving most of the normal liver cells. In practice, this may be accomplished by injecting a hepatic artery with embolic material (which obstructs the vessel with a clot or foreign substance) or by surgical ligation of a hepatic artery. However, in time new blood vessels develop, which restores circulation to the remaining tumor cells.

In some cases, hepatic artery embolization is accompanied by the administration of chemotherapy agents. The chemotherapy acts directly to destroy tumor cells in the liver. And, by administration into a hepatic artery, chemotherapy agents are present in reduced quantities in other areas of the body and, therefore, cause a reduced incidence of toxic effects.

Medical Therapy

Octreotide Acetate

Octreotide acetate therapies such as Sandostatin LAR® Depot (octreotide acetate for injectable suspension) block the release of bioactive substances from carcinoid tumors. Also, like somatostatin, Sandostatin LAR® Depot exerts direct effects on the gastrointestinal tract itself; it prolongs intestinal transit time (2). By doing so, it can significantly reduce symptoms (notably, diarrhea and flushing) that are associated with excess quantities of these bioactive substances.

Despite the established efficacy of octreotide acetate and its advantages over native somatostatin, the inconvenience of multiple daily subcutaneous injections to maintain therapeutic drug levels has remained a practical deterrent to both patients and physicians. A long-acting release formulation, Sandostatin LAR® Depot, was developed to address the limitations of the immediate release Sandostatin® Injection formulation. (3, 4):

• Sandostatin LAR® Depot incorporates octreotide into microspheres of the biodegradable glucose star polymer, D,L-lactic and glycolic acids < copolymer (3).
• Slow drug release accompanies the biodegradation of the polymer ester bond through hydrolysis (5).
• The short-acting formulation can be used for additional control of symptom flare ups.

Interferon

Interferon has been shown to reduce hormone production from carcinoid tumors. In about half to two thirds of patients in clinical trials, this has been accompanied by reduction in symptoms (6). In a few patients, interferon has also reduced tumor size. (In several small trials, response rates ranged from 0% to 20% (7).)

Interferon is usually administered 3 times a week, in doses of approximately 3 to 9 million units given by subcutaneous or intramuscular injection (7). Most patients experience flu-like symptoms (fever, fatigue, muscle pain) for a few days after administration. Other side effects, including loss of appetite, weight loss, and anemia have also been noted.

Chemotherapy

During the 1970s and 1980s, chemotherapy was frequently used to try to reduce the growth of primary and metastatic carcinoid tumors. However, since chemotherapy typically produced poor results (with partial responses in no more than 20% to 30% of patients) and was associated with significant toxicity, chemotherapy now has a greatly reduced role (8).

Some chemotherapy regimens that have been used for the treatment of carcinoid tumors and VIPomas include:

• 5-fluorouracil and leukovorin
• cyclophosphamide, doxorubicin, and cisplatin
• dacarbazine and 5-fluorouracil
• etoposide and cisplatin

Radiotherapy

Radiation therapy may be used to address specific symptoms (e.g., pain resulting from bone metastasis) that may be present in certain patients with carcinoid syndrome. However, it is not useful in treating metastases in the liver or other nonskeletal tissues.