TGCT patients that are on medications for their TGCT may side effects. While these medications help shrink TGCT and reduce symptoms associated with TGCT, there are some common side effects to be aware of. The most common side effects are facial swelling (especially around the eyes), rash, itching, loss of energy or tiredness, nausea, headaches, and diarrhea. Some specific TGCT medications have unique side effects such as change in skin and hair pigment (observed in patients receiving pexidartinib). In order to cope with side effects, doctors may interrupt your treatment (i.e., recommend a break), prescribe or recommend other drugs to be given in combination with your treatment, or discontinue treatment entirely. Consult with your care team for a proactive plan to prevent several side effects such as nausea and itching.
Information regarding common side effects and management are below:
Some patients experience nausea while taking TGCT medications. Antiemetics are a drug class of medications that prevent vomiting and nausea. These drugs treat motion sickness, drug side effects, post-surgery nausea, and in some cases, nausea associated with pregnancy. Often times these drugs can be taken through a dissolvable tablet, a capsule, or a skin patch. The two most commonly prescribed antiemetic are ondansetron (Zofran) and promethazine (Phenergan). These medications work differently to combat nausea. For instance, 1) ondansetron works by blocking a signaling molecule called serotonin in your brain. This disrupts the signal between your brain and your gut, reducing the signal creating the nausea; 2) phenergan works by blocking another molecule called histamine in your brain. This allows your brain to signal to your gut to relax. Other anti-histamines, such as Benadryl, can block histamine signaling and lead to decreased nausea.
There are two main classes of medications used to treat constipation. These drugs can be taken orally or through suppositories. They can be broken down into Laxatives and Surfactants:
Laxatives: Laxatives work by stimulating bowel movement. This simulation can help speed up movement through the gastrointestinal tract. Some laxatives work by increasing the water and bulk of the stool, allowing stool to move through the gastrointestinal tract undigested. The other type of laxative increases bowel movement frequency by causing the colon to retain water.
Surfactants: Surfactants, also known as stool softeners, work by increasing the amount of water absorbed in stool. This allows more moisture to be absorbed, leading to softened stool that can move through the gastrointestinal tract easier. The most commonly prescribed surfactants is docusate (Colace, Doculax).
Swelling, often in the face and around the eyes, is caused by excessive fluid trapped in your body's tissue. Commonly, the swelling is observed either in the limbs or face and can be a side effect of these TGCT medications. It is not entirely understood why fluid retention is a side effect of these medications; however, scientists think the swelling is due to impaired draining of fluid. Inflammatory/immune cells are part of the fluid drainage system in your body which these TGCT medications inhibit. Therefore, it's possible that fluid isn't draining as fast, causing puffiness. To combat this, it is important to drink more water than usual. Often times when you're dehydrated, your body holds onto water. Therefore it's important you consume around 3.7 liters (men) and 2.7 liters (women), also calculated as half your body weight (lbs) in ounces (5). However, if significant swelling has occurred, a medication called a diuretic may be used. One of the most commonly prescribed diuretic is furosemide (Lasix). Your body's water retention is regulated by systemic sodium concentrations. Most of these medications that reduce swelling help rid your body of water through releasing more sodium in your urine. While the sodium leaves your body, it brings water from the blood along with it. This can also reduce blood pressure.
Many CSF1 inhibitors result in itching, also called pruritus. Reduction in CSF1 in cells may stimulate itch-sensitive nerves, this is common with many drugs that stimulate cells that also release histamines, a chemical in your body that's known for its role in causing allergy symptoms. Thus, the treatment for drug-induced itching is often anti-histamines like benadryl (diphenhydramine) or zyrtec (cetirizine).
A rash is the change in appearance or feel of the skin often characterized by redness, raised appearance, itching, or swelling. CSF1 inhibitors may lead to rash as CSF1 plays a critical role in the immune system in skin inflammation. Many patients on CSF1 inhibitors for TGCT may develop a rash at some point in their treatment. If so, these rashes are commonly monitored and may never require treatment. If treatment is needed because the rash is large, uncomfortable, or spreading, corticosteroid ointment or topical treatment are often prescribed. Dose interruptions or modification can also be used to reduce the extent or frequency of rashes.
Lab abnormalities
Many CSF1 inhibitors can cause changes in certain lab values, including AST, ALT, bilirubin, creatinine phosphokinase (also called creatinine kinase), and LDH. These changes are usually asymptomatic, meaning patients don’t feel any different, but they are monitored closely because they can signal organ stress or injury. In particular, AST, ALT, and bilirubin are used to check liver function. A single abnormal value on its own may not mean much, but when changes occur together, they can help doctors decide if a dose adjustment or treatment break is needed. The exact lab tests and frequency of monitoring depend on the specific medication you are taking, so it’s important to discuss with your doctor which tests you need and how to understand the results.
References
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