by Monica Davey

Oral therapies have enabled many types of cancer to be considered treatable chronic diseases. Oral chemotherapy is effective only if you adhere to its administration schedule. Side effects may prevent some people from taking their medication as prescribed. Knowing potential side effects and interventions may minimize their ill effects.

Currently there are two approved oral therapies for the management of GIST – imatinib mesylate (Gleevec©) and sunitinib malate (Sutent©).

Frequently seen Gleevec side effects include:

  • Superficial edema (the most common)

  • Diarrhea
  • Nausea/vomiting
  • Abdominal pain
  • Fatigue
  • Muscle cramps
  • Rash

Frequently seen Sutent side effects include:

  • Fatigue (the most common)
  • Rash/dermatitis and discoloration of skin
  • Hypertension, headache
  • Arthralgias, edema
  • Nausea/vomiting, diarrhea, altered taste
  • Dyspepsia, stomatitis
  • Anemia, neutropenia, thrombocytopenia
  • Hypothyroidism

How do we manage these potential side effects??

Fluid retention (edema) is swelling caused by the abnormal buildup of fluid in the body. Fluid collects under the skin within the tissues that are outside of the circulatory system. Superficial edema is most common in the feet and legs, but can also occur in the hands, arms, and face (periorbital or under the eyes). It is suggested that you weigh yourself twice a week and notify your health care provi

der if you gain more than five pounds above your normal weight. Management of edema may be accomplished by a low salt diet and if your physician feels it to be necessary, a mild diuretic may be prescribed.

Gastrointestinal side effects may include nausea, vomiting, or diarrhea. To avoid this Gleevec (and Sutent?) should be taken with food and a large glass of water. Remain upright for about an hour. If nausea is persistent, your physician may prescribe antinausea medicine. Antidiarrheal medicine may be used for persistent diarrhea. Grapefruit juice/grapefruit products may increase plasma concentration of Gleevec and should be avoided. Stool softeners may be used for constipation. When taking Sutent, some foods may cause your mouth to feel sensitive, altering your taste. Diet modification may be necessary, such as avoidance of spicy food. Good oral hygiene is recommended along with avoidance of products with alcohol as an ingredient. Stomatitis is inflammation of the mucous lining of any of the structures in the mouth. It is managed symptomatically. Dyspepsia, commonly known as indigestion or reflux, is characterized by chronic or recurrent pain or discomfort in the upper abdomen. This also includes feeling full earlier than expected when eating. This reflux can be managed symptomatically with antacids, proton pump inhibitors or H-2 inhibitors. Your healthcare provider will assist you in making the decision of which is best for you to use. Previous surgery in the stomach/GI tract may make you prone to reflux or diarrhea. Flatulence (gas) may occur and many describe relief from simethicone use.

Fatigue may occur and may be self limiting. It may also be a sign of anemia, or low red cell count in your blood. If you feel tired, rest if you can.

Hypertension or high blood pressure may be defined as blood pressure of 140/90 or above. This often occurs when taking Sutent. You are encouraged to monitor your blood pressure and being aware of subtle symptoms like headache, which may indicate your blood pressure is elevated. Notify your healthcare provider who may prescribe an antihypertensive medicine. If you are currently receiving an

tihypertensive medicine, it may be increased or additional medicine may also be prescribed. In cases of severe hypertension, temporary suspension of Sutent may be recommended until your blood pressure is controlled. A low salt diet is recommended.

Myalgias (muscle cramps) may occur in the hands, feet and/or legs. They are usually occasional in nature and may increase with prolonged therapy. They may be mitigated by increasing oral fluid intake on a regular basis. Arthralgias (joint pain) may be exacerbated especially when taking Sutent. Regular use of nonsteroidal anti-inflammatory (NSAIDs) medications may provide relief.

Skin rash or other dermatologic side effects may also be seen when taking Sutent and Gleevec. The majority of rashes consist of red, scaly bumps on the face, arms or trunk which may become itchy. A higher risk of developing a rash may be associated with higher Gleevec doses, advanced age, and female gender. Rash usually resolves with the use of topical or oral diphenhydramine hydrochloride (Benadryl ©). In some cases steroids may be used. Your health care provider may elect to interrupt your therapy if your rash is severe. Sutent may cause a hand foot skin reaction which is thick, scaly areas in the palms and soles of the feet. It may look and feel like calluses or warts and it may be painful. It is suggested that you keep your skin well moisturized. Skin and/or hair discoloration may also occur with Sutent. Skin may become pale and yellow while the hair may become gray/white.

Low blood counts may also temporarily occur while taking oral chemotherapy. White and red blood cells and platelets may temporarily decrease which would put you at risk for infection, anemia and or bleeding. Low red blood cell counts (anemia) may cause you to feel tired (fatigue).

Thyroid dysfunction (mostly hypothyroidism) is a disorder in which your thyroid gland cannot produce an adequate amount of certain important hormones. Thyroid function will be monitored by blood tests. Your physician may consider thyroid supplementation if necessary.

Rare but potentially serious side effects:

Hepatic impairment is an abnormal reduction in liver function. Liver function will be monitored by blood testing. It is recommended that Acetaminophen containing products be taken according to the package insert. In addition, alcohol consumption should be minimized.

Renal impairment i

s characterized by the kidney’s inability to filter wastes from the blood. Close monitoring of renal function by blood testing is recommended.

Heart problems including left ventricular dysfunction is a condition in which the left ventricle (a chamber of the heart) does not pump effectively. This may lead to congestive heart failure, heart attack or other cardiovascular complications. Your physician may order an echocardiogram which is a test that measures the left ventricular ejection fraction (the amount of blood pumped) as well as the level of motion of the left ventricular wall.

Conclusion

You may experience other side effects that have not been described here. Please discuss any side effects you may be experiencing with your health care provider. While these medications are generally well tolerated, the majority of patients will experience mild to moderate side effects at some time. More severe side effects are rare. Many side effects are reversible upon discontinuation of therapy.

Potential drug interactions may occur. Review your list of medications with your health care provider and/or your pharmacist. Drug-food interactions may also occur.

In order to ensure the drug’s effectiveness, take your medication as directed and avoid missing any doses. Be mindful that no

t all pharmacies stock these drugs, and it may take a few days to get them. Discuss this with your pharmacy to ensure no doses are missed during the waiting period.

Best of luck and remember to keep open communication with your health care providers and pharmacists.

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Monica Davey

Clinical Research Nurse Coordinator
Fox Chase Cancer Center
Philadelphia, Pennsylvania

Monica P. Davey, RN, BSN, M.Ed, MBA, is a clinical research coordinator at the Fox Chase Cancer Center and administrative supervisor at Aria Health (Frankford Hospital)-Torresdale Division in Philadelphia, Pennsylvania. Prior to her current positions, she served as head nurse in the Emergency Department and staff development critical care/trauma educator at Aria Health (Frankford Hospital)-Torresdale Division. Ms. Davey earned her diploma in nursing from Abington Memorial Hospital School of Nursing, a bachelor of science in nursing at Gwynedd-Mercy College, a master of education in major health education at Pennsylvania State University and a master of business administration in management and a postgraduate certificate in clinical research operations at LaSalle University.

Ms. Davey is a member of the Society of Clinical Research Associates, the Oncology Nursing Society and the Eastern Cooperative Oncology Group. She has coordinated and taught numerous continuing medical education programs and has given presentations at the educational incentives for Patient Management and Compliance Issues with New Oral Oncology Therapies, Novel Cancer Therapies Grand Rounds, and gave a presentation entitled Management of Imatinib Mesylate (Gleevec) Complications, at a GIST Symposium. She has authored, or co-authored articles appearing in journals such as Clinical Cancer Research, Sarcoma, Clinical Journal of Oncology Nursing, and Cancer Research.