Other Drugs for Pancreatic Neuroendocrine Tumors

Somatostatin analogs

Somatostatin analogs are compounds similar to somatostatin, a natural hormone in the body. They can help slow the growth of neuroendocrine tumor cells. They can be very helpful for patients with pancreatic NETs that have somatostatin receptors. When somatostatin analogs bind to the somatostatin receptors on cancer cells, they may stop the cancer cells from releasing hormones into the bloodstream, which can often relieve symptoms and help patients feel better. These analogs also seem to help slow the growth of some tumors, but cannot cure them.

These drugs can help reduce side effects, such as diarrhea in patients with VIPomas and help the skin rash of glucagonomas. They, however, may not be as effective in treating low blood sugar in patients with insulinomas or treating increased stomach acid production in patients with gastrinomas.

They are very useful in people who have carcinoid syndrome (facial flushing, diarrhea, wheezing, rapid heart rate), although this syndrome is not as common with NETs in the pancreas as it is with NETs found in other places.

• Octreotide (Sandostatin): One version of octreotide is short-acting and is injected 2 to 4 times a day under the skin. There is also a long-acting form of the drug (called Sandostatin LAR Depot) that only needs to be given once a month, by injection into a muscle. Depending on the severity of symptoms, some people are given injections every day when first starting treatment. Once symptoms are controlled, the longer-acting monthly injection may then be used. Other times, the long-acting drug may be started from the beginning.
• Lanreotide (Somatuline Depot): This is a long-acting somatostatin analog. It is given once a month, by injection under the skin.

Either drug may be given by your doctor or nurse, or you may learn how to give the injection at home.

Possible side effects of somatostatin analogs

The main side effects of these drugs are pain at the site of the injection, and rarely, stomach cramps, nausea, vomiting, headaches, dizziness, and fatigue. These drugs can also cause sludge to build up in the gallbladder, which can lead to gallstones that usually do not cause symptoms. They can also make the body resistant to the action of insulin, which can raise blood sugar levels and make pre-existing diabetes harder to control.

Pembrolizumab (Keytruda)

Pembrolizumab is a type of immunotherapy drug known as an immune checkpoint inhibitor. It works on PD-1, a protein on immune cells called T cells that normally helps keep them from attacking other cells in the body (including cancer cells). By blocking PD-1, pembrolizumab boosts the immune response against cancer cells. This can shrink some tumors or slow their growth.

This drug might be an option to treat some advanced cancers, typically after other treatments have been tried or when no other good treatment options are available, if the cancer cells have any of the following:

•     A high level of microsatellite instability (MSI-H) or a defect in a mismatch repair gene (dMMR)
•     A high tumor mutational burden (TMB-H), meaning the cancer cells have many gene mutations

This drug is an intravenous (IV) infusion, typically given every 3 or 6 weeks.

Other approved uses of this drug: Pembrolizumab can also be used to treat people with many other specific types of cancer, such as lung cancer and melanoma skin cancer.

Possible side effects of pembrolizumab

Common side effects include fatigue, muscle and joint pain, cough, rash, fever, nausea, abdominal (belly) pain, constipation, poor appetite, shortness of breath, low thyroid hormone levels, and diarrhea.

Infusion reactions: Some people might have an infusion reaction while getting this drug. This is like a serious allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting a pembrolizumab infusion.

Autoimmune reactions: This drug basically removes one of the safeguards on the body’s immune system. Sometimes this causes the immune system to attack other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, skin, or other organs.

It’s very important to report any new side effects to your health care team right away. If you do have a serious side effect, treatment may need to be stopped and you may be given high doses of corticosteroids to suppress your immune system.

Other drugs used for specific pancreatic NETs

Other drugs may be used to treat specific symptoms or problems that are caused by the excess hormone being produced by pancreatic NETs. .

Proton pump inhibitors

Gastrinomas make too much gastrin, which increases stomach acid levels, and can lead to stomach ulcers. Proton pump inhibitors, for example omeprazole (Prilosec), esomeprazole (Nexium), or lansoprazole (Prevacid), block stomach acid production and may be given to decrease the chance of ulcers forming.  

Diazoxide   

Insulinomas make too much insulin which causes very low blood glucose (sugar) levels. Diazoxide, a drug that keeps insulin from being released into the bloodstream, or diet changes (higher carbohydrate intake or more frequent meals) may be started to raise glucose levels.

Diabetes drugs

Glucagonomas make too much glucagon, a hormone that increases blood glucose (sugar) levels. It works the opposite of insulin. These cancers may be treated with medicines for diabetes if somatostatin analogs alone are not enough to control the high glucose levels.

IV fluids 

VIPomas make too much vasoactive intestinal peptide (VIP), a hormone that regulates water and mineral (such as potassium and magnesium) levels in the gut. Treatment may involve giving intravenous (IV) fluids to treat the dehydration from diarrhea as well as replace certain minerals that are low.