Trabectedin (Yondelis®)

Trabectedin damages cancer cells through a process called alkylation. Alkylation damages the DNA of cells, which prevents them from dividing, and causes them to die. Since cancer cells, in general, divide faster, and with less error-correcting than healthy cells, they are more sensitive to this damage.

How to Take Trabectedin

Trabectedin is administered intravenously (IV, into a vein), preferably through a central line catheter. Prior to each treatment with this medication, you will be given a steroid medication, called dexamethasone, to help prevent a reaction. The dose you receive is based on your weight, your lab values, and the intensity of side effects you are experiencing. Your dose may be reduced or discontinued depending upon the severity of the side effects. It may also be adjusted based on your lab values such as absolute neutrophil count, platelets, and liver and heart function tests.

The blood levels of this medication can be affected by certain foods and medications, so they should be avoided. These include grapefruit, grapefruit juice, verapamil, ketoconazole, rifampin, phenytoin, St. John’s wort, and modafinil. Be sure to tell your healthcare provider about all medications and supplements you take.

Even when carefully and correctly administered by trained personnel, this drug may cause a feeling of burning and pain. There is a risk that this drug may leak out of the vein at the injection site, resulting in tissue damage that can be severe. If the area of injection becomes red, swollen, or painful at any time during or after the injection, notify your doctor or nurse immediately. Do not apply anything to the site unless instructed by your doctor or nurse.

Possible Side Effects of Trabectedin

There are a number of things you can do to manage the side effects of trabectedin. Talk to your care team about these recommendations. They can help you decide what will work best for you. These are some of the most common or important side effects:

Low Red Blood Cell Count (Anemia)

Your red blood cells are responsible for carrying oxygen to the tissues in your body. When the red cell count is low, you may feel tired or weak. You should let your oncology care team know if you experience any shortness of breath, difficulty breathing, or pain in your chest. If the count gets too low, you may receive a blood transfusion.

Liver Toxicity

This medication can cause liver toxicity, which your doctor may monitor for using blood tests called liver function tests. Notify your healthcare provider if you notice yellowing of the skin or eyes, your urine appears dark or brown or pain in your abdomen, as these can be signs of liver toxicity.

Low White Blood Cell Count (Leukopenia or Neutropenia)

White blood cells (WBC) are important for fighting infection. While receiving treatment, your WBC count can drop, putting you at a higher risk of getting an infection. You should let your doctor or nurse know right away if you have a fever (temperature greater than 100.4 °F or 38°C), sore throat or cold, shortness of breath, cough, burning with urination, or a sore that doesn't heal.

Tips to preventing infection:

• Washing hands, both yours and your visitors, is the best way to prevent the spread of infection.
• Avoid large crowds and people who are sick (i.e.: those who have a cold, fever, or cough or live with someone with these symptoms).
• When working in your yard, wear protective clothing including long pants and gloves.
• Do not handle pet waste.
• Keep all cuts or scratches clean.
• Shower or bathe daily and perform frequent mouth care.
• Do not cut cuticles or ingrown nails. You may wear nail polish, but not fake nails.
• Ask your oncology care team before scheduling dental appointments or procedures.
• Ask your oncology care team before you, or someone you live with has any vaccinations.

Low Platelet Count (Thrombocytopenia)

Platelets help your blood clot, so when the count is low you are at a higher risk of bleeding. Let your oncology care team know if you have any excess bruising or bleeding, including nose bleeds, bleeding gums, or blood in your urine or stool. If the platelet count becomes too low, you may receive a transfusion of platelets.

• Do not use a razor (an electric razor is fine).
• Avoid contact sports and activities that can result in injury or bleeding.
• Do not take aspirin (salicylic acid), non-steroidal, anti-inflammatory medications (NSAIDs) such as Motrin/Advil (ibuprofen), Aleve (naproxen), Celebrex (celecoxib), etc. as these can all increase the risk of bleeding. Please consult with your healthcare team regarding the use of these agents and all over-the-counter medications/supplements while on therapy.
• Do not floss or use toothpicks and use a soft-bristle toothbrush to brush your teeth.

Nausea and/or Vomiting

Talk to your oncology care team so they can prescribe medications to help you manage nausea and vomiting. In addition, dietary changes may help. Avoid things that may worsen the symptoms, such as heavy or greasy/fatty, spicy or acidic foods (lemons, tomatoes, oranges). Try antacids, (e.g. milk of magnesia, calcium tablets such as Tums), saltines, or ginger ale to lessen symptoms.

Call your oncology care team if you are unable to keep fluids down for more than 12 hours or if you feel lightheaded or dizzy at any time.

Fatigue

Fatigue is very common during cancer treatment and is an overwhelming feeling of exhaustion that is not usually relieved by rest. While on cancer treatment, and for a period after, you may need to adjust your schedule to manage fatigue. Plan times to rest during the day and conserve energy for more important activities. Exercise can help combat fatigue; a simple daily walk with a friend can help. Talk to your healthcare team for helpful tips on dealing with this side effect.

Kidney Problems

This medication can cause kidney problems, including an increased creatinine level, which your oncology care team may monitor for using blood tests. Notify your healthcare provider if you notice decreased urine output, blood in the urine, swelling in the ankles, or loss of appetite.

Decrease in Appetite

Nutrition is an important part of your care. Cancer treatment can affect your appetite and, in some cases, the side effects of treatment can make eating difficult. Ask your oncology care team about nutritional counseling services at your treatment center to help with food choices.

• Try to eat five or six small meals or snacks throughout the day, instead of 3 larger meals.
• If you are not eating enough, nutritional supplements may help.
• You may experience a metallic taste or find that food has no taste at all. You may dislike foods or beverages that you liked before receiving cancer treatment. These symptoms can last for several months or longer after treatment ends.
• Avoid any food that you think smells or tastes bad. If red meat is a problem, eat chicken, turkey, eggs, dairy products, and fish without a strong smell. Sometimes cold food has less of an odor.
• Add extra flavor to meat or fish by marinating it in sweet juices, sweet and sour sauce, or dressings. Use seasonings like basil, oregano, or rosemary to add flavor. Bacon, ham, and onion can add flavor to vegetables.

Constipation

There are several things you can do to prevent or relieve constipation. Include fiber in your diet (fruits and vegetables), drink 8-10 glasses of non-alcoholic fluids a day, and keep active. A stool softener once or twice a day may prevent constipation. If you do not have a bowel movement for 2-3 days, you should contact your healthcare team for suggestions to relieve the constipation.

Diarrhea

Your oncology team can recommend medications to relieve diarrhea. Also, try eating low-fiber, bland foods, such as white rice and boiled or baked chicken. Avoid raw fruits, vegetables, whole-grain breads, cereals, and seeds. Soluble fiber is found in some foods and absorbs fluid, which can help relieve diarrhea. Foods high in soluble fiber include applesauce, bananas (ripe), canned fruit, orange sections, boiled potatoes, white rice, products made with white flour, oatmeal, cream of rice, cream of wheat, and farina. Drink 8-10 glasses of non-alcoholic, un-caffeinated fluid a day to prevent dehydration.

Rhabdomyolysis

Rhabdomyolysis is a condition in which muscle damage occurs and breaks down, releasing cells into the bloodstream. This quick breakdown of muscle cells can become severe and lead to kidney damage and even death. Notify your provider if you develop muscle pain or weakness, confusion, vomiting, and dark or brown-colored urine.

Peripheral Edema

Peripheral edema is swelling of the extremities caused by the retention of fluid. It can cause swelling of the hands, arms, legs, ankles, and feet. The swelling can become uncomfortable. Notify your oncology care team if you are experiencing any new or worsening swelling.

Headache

Your doctor or nurse can recommend medication and other strategies to relieve pain.

Shortness of breath

Trabectedin may cause shortness of breath, which can happen on its own or due to a low red blood cell count or infection. No matter the cause, it is important to call your provider immediately with any signs of shortness of breath. These include chest tightness, wheezing, a new or worsening cough, shallow breathing, or congestion. If you can’t seem to catch your breath or if you have chest pain, call 911.

Important but Less Common Side Effects

• Allergic Reactions: In some cases, patients can have an allergic reaction to this medication. Signs of a reaction can include shortness of breath or difficulty breathing, chest pain, swelling of the lips, rash, flushing or itching, or a decrease in blood pressure. If you notice any changes in how you feel during the infusion, let your nurse know immediately. The infusion will be slowed or stopped if this occurs. Depending on the severity of your reaction, you may still be able to receive the medication with a pre-medication to prevent a reaction, or if the medication is given at a slower rate.
• Heart Problems: This medication can cause or worsen pre-existing heart problems including congestive heart failure, restrictive cardiomyopathy, and decreased heart function. Your provider will order a test to check your heart function before starting this medication. Notify your healthcare provider if you have sudden weight gain or swelling in the ankles or legs. If you develop chest pain, shortness of breath, palpitations, lower extremity swelling, or fatigue, notify your provider or call 911.
• Capillary Leak Syndrome: Capillary leak syndrome is a condition in which blood, and components of blood, leak out of vessels and into body cavities and muscles. The movement of this fluid out of the vessels can cause hypotension (low blood pressure) and organ failure. Signs and symptoms of capillary leak syndrome include a sudden drop in blood pressure, weakness, fatigue, sudden swelling of the arms, legs, or other parts of the body, nausea, and lightheadedness. If you are having any of these symptoms notify your healthcare provider immediately.

Reproductive Concerns

Exposure of an unborn child to this medication could cause birth defects, so you should not become pregnant or father a child while on this medication. Effective birth control is necessary during treatment and for at least 2 months after treatment for women, and for at least 5 months after treatment for men. Even if your menstrual cycle stops or you believe you are not producing sperm, you could still be fertile and conceive. You should consult with your healthcare team before breastfeeding while receiving this medication.