Organ Toxicity
Practically every type of cancer therapy, including radiation, chemotherapy, targeted and biologic agents, could cause organ toxicity. Some types of damage are transient and/or reversible, while other injuries might be delayed and/or permanent. The likelihood of this complications is not high, but they occasionally might be severe and even life-threatening. The primary organs that may be affected are the heart, lungs, liver and kidneys.
Different medications affect our organs in different ways. It will be very confusing to describe all possible problems in one small section. Instead, we will discuss specific medication choices before initiating you treatment and inform you about their potential for organ damage. We will also identify risk factors for developing these complications and, if necessary, either select an alternative drug, or watch you very carefully.
Unfortunately, we are unable to predict who will develop problems, but we will try to identify them early and intervene on time. All persons receiving drugs with a potential for organ damage will be closely monitored through careful physical assessment prior to the start of therapy and at each subsequent visit, lab work and other tests such as MUGA scans (heart) or PFTs (pulmonary function test for the lungs).
Heart
Damage to the heart by chemotherapy or targeted agents is called cardiac toxicity. Cardiac toxicity may present in different ways, including change in the heart rhythm, constriction of the vessels supplying the heart or decreased ability of the heart muscle to pump blood (congestive heart failure). Although relatively rare, some of these effects may be irreversible or permanent and they may occur early in therapy (acute toxicity) or years later. In this section we will discuss the most common drugs which can potentially cause this problem.
The most common chemotherapeutic agents that can cause cardiac toxicity belong to a class of drugs referred to as anthracyclines. This class of drugs includes Doxorubicin, Epirubicin, Daunorubicin, Idarubicin and Mitoxantron. These drugs are used to treat a wide variety of cancers including breast cancers, leukemias and lymphomas. The targeted agent most often associated with cardiac toxicity is Herceptin; it is used in treatment of breast cancer.
There are conflicting results as to how often treatment with anthracyclines and/or Herceptin leads to congestive heart failure and how reversible is this damage.
Risk factors for developing cardiac toxicity include:
ØTotal amount of the drug received over your lifetime. Your doctor and nurse keep track of how much of a particular drug you receive.
ØThe dosing schedule.
ØAge greater than 50 years.
ØPre-existing damage to the heart.
ØReceiving combination chemotherapy where more than one drug in the regimen may have the potential to cause heart damage (i.e. Doxorubicin and Cytoxan).
ØPrevious or current radiation to the mediastinum (chest).
Cardiac Toxicity is monitored a number of ways:
ØPrior to start of your therapy your doctor will order a MUGA scan. This test will give the doctor information about how well your heart muscle works now.
ØEKG – this test measures the rate and regularity of your heart.
ØChest X-ray – this can show us a picture of your heart and allow us to see any obvious damage such as an enlarged heart muscle.
ØYour doctor will always listen to your heart prior to the start of each cycle of chemotherapy. Extra sounds or unusual sounds can give us a clue that we need to do further testing.
Things that we can do to help prevent or lessen the risk for cardiac toxicity are:
ØStaying under the accepted cumulative lifetime dose of the drug being used. For patients who receive doses less than their cumulative lifetime levels, the risk for cardiac toxicity is less than 1%. Exceeding lifetime doses increases the risk to 30%.
ØAdministering the drugs in an infusion of saline rather than as a bolus dose.
ØUse of liposomal formulations of doxorubicin and daunorubicin. Liposomal formulations encase the drug in a tiny globule of fat. By “hiding” the drug it stays in the system longer but causes less damage to normal tissues.
ØChecking the function of your heart before, during and after treatment in order to intervene on time
Cardiac toxicity is a serious problem. If you experience any of the following, call your doctor immediately:
ØFatigue
ØShortness of breath on exertion
ØWorsening of already existing shortness of breath.
ØSwelling in the ankles.
ØA gain of more than 3 -5 pounds in one week.
ØFeeling short of breath when lying on your back.
The Kidneys
Kidney damage in cancer patients may occur through mechanisms unrelated to chemotherapy: a decrease in blood supply to the kidney caused by drugs or infection; a blockage in the urinary system by tumor; damage to kidney cells by substances actively produced by tumor cells or released after tumor cell death (see Tumor Lyses Syndrome).
Some chemotherapy and biotherapy drugs can also cause damage to the kidney resulting in acute renal failure. The most common agents among them are Cisplatin, Cytarabine, Ifosfamide, Streptozocin and Interlukin-2. Patients receiving these drugs may have more than a 30% chance of developing some type of kidney damage; however, if it is identified early and managed appropriately it can, in most cases, be reversed.
Risk factors for developing kidney toxicity include:
ØPre-existing kidney disease
ØUse of combination therapy in which there are two or more medications within the combination that have the potential for causing kidney toxicity
Renal toxicity is monitored by checking blood levels of two products, blood urea nitrogen (BUN) and creatinine. BUN is a waste product created from the breakdown of a protein called urea. Urea circulates in the blood until it is filtered out by the kidneys and excreted in the urine. If the kidneys are not functioning properly, there will be elevated levels of urea in the bloodstream. A normal BUN level ranges from 10 to 25 mg/dl of blood. Creatinine is a waste product released from your muscles. If your kidneys are not functioning properly they will not be able to filter out creatinine and the creatinine level in your blood will rise. Normal creatinine levels range from 0.7 to 1.4 mg/dl of blood.
It is not uncommon to see changes in your urine as a result of kidney damage due to cancer itself, cancer therapy or infection. Changes in color, the presence of blood in your urine or changes in the amount of times you urinate and the amount of urine you pass can be indicative of damage to the kidney, blockage in the urinary tract or urinary tract infection.
If you experience any of the following call your physician:
Ø Decrease in amount of urine or frequency
ØPain or urgency with urination
ØDark urine
ØBlood in your urine
ØFatigue
ØMuscle weakness
ØSwelling in your feet or ankles
ØUnexplained nausea or vomiting
ØConfusion, seizure
Things that we may do to help:
ØWhen we are giving you drugs that are known to cause kidney damage, we may give you extra fluids before and/or after your treatment.
ØWe will ask you to drink a minimum of 64 ounces of non-alcoholic, non-caffeinated fluids daily (unless on fluid restriction by another physician).
The Bladder
Some chemotherapy can cause irritation to the bladder, which can result in temporary or permanent damage. This irritation is referred to as cystitis. Cystitis can also occur when you have a bladder infection. Cystitis secondary to chemotherapy can be mild to severe. If there is bleeding into the urine, it is referred to as hemorrhagic (bleeding) cystitis.
Drugs most commonly associated with bladder toxicity are Cyclophosphamide (Cytoxan) and Ifosfamide. When these drugs are broken down in the body, some of the resulting by-products are disposed of in the urine and can irritate the lining of the bladder as urine passes through or when urine sits in the bladder prior to being excreted.
Patients receiving chemotherapy directly into the bladder via catheter instillation are also at risk for bladder damage. The drugs most commonly associated with this type of administration are Mitomycin-C, Thiotepa, or Doxorubicin. Cystitis can also occur to patients receiving radiation therapy to the pelvic region (prostate or bladder cancers). Symptoms caused by radiation may not appear for several months after treatment.
Call your doctor if you experience any of the following symptoms of:
ØUrinary frequency
ØUrinary urgency
ØBurning with urination
ØPainful urination
ØInability to empty the bladder completely
ØUrinary incontinence
ØBlood in the urine
ØAbdominal pain
Things that we may do to help:
ØWhen we are giving you drugs that are known to cause bladder damage we may give you extra fluids before and/or after your treatment.
ØWe will ask you to drink a minimum of 64 ounces of non-alcoholic, non-caffeinated fluids daily (unless on fluid restriction by another physician). Drinking plenty of fluids will ensure good urine flow and help to prevent problems. A high flow of urine will dilute the metabolites in the urine and reduce contact between those metabolites and the bladder.
ØIn some cases your physician may order the use of a drug called Mesna. This drug has been shown to prevent Cyclophosphamide and Ifosfamide induced cystitis. It works by binding to the metabolite acrolein in the bladder to form an inactive product that is then excreted. In this way, the bladder is protected, but the antitumor activity of the chemotherapy drug remains the same.
Liver
The liver is the largest organ in the body and serves many vital functions. It’s most important job is to filter out toxins, including alcohol and many different drugs. The liver changes drugs and toxins into products that can be easily removed through bile or urine. If there are more toxins than the liver can handle, it may not function normally. Accumulations of toxins in the liver can cause temporary or permanent damage. This damage is referred to as hepatotoxicity.
Nearly every chemotherapy drug has the potential to cause some type of liver damage as almost all of them are filtered through the liver. The risk of liver toxicity depends on the drug and on the pre-existing “state of health” of your liver and biliary system.
The most common way to monitor for liver toxicity is through blood tests. Your doctor will do these tests routinely, prior to each treatment cycle and in between if necessary.
Routine blood work includes:
ØBilirubin - bilirubin is a chemical that is formed during the regular breakdown of red blood cells and excreted from the liver in the bile. When liver cells are damaged, they may not be able to excrete bilirubin in the normal way. Blockage of the biliary system by tumor or stricture can also interfere with excretion of the bilirubin. Abnormal excretion of bilirubin causes its buildup in the blood and can be detected with a blood test.
ØLiver enzymes -Enzymes are proteins that trigger important chemical reactions in the body. Blood levels of several enzymes that are produced in the liver may be elevated if the liver is damaged.
o Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) rearrange the building blocks of proteins. They are released from damaged liver cells.
o Lactate dehydrogenase is involved in producing energy. It is released from damaged cells in many areas of the body, including the liver.
ØAlkaline phosphataseis involved in bone growth and excreted in the bile. It may be elevated if bile excretion is inhibited by liver damage.
To determine the cause of liver abnormalities identified in the blood work, your physician may order other tests:
ØCT Scan or MRI
ØERCP (endoscopic retrograde cholangiopancreatography)
ØLiver Biopsy
Liver damage is a serious problem. Please notify your doctor if you experience any of the following:
ØAny unusual swelling in your feet, legs or abdomen, or a weight gain of 3-5 pounds in one week.
ØYellowing of the skin, whites of the eyes, and mucous membranes. This is referred to as jaundice and may occur secondary to high levels of bilirubin in the extracellular fluid.
ØGeneralized itching.
ØNew rashes.
ØAbdominal pain, severe nausea, and vomiting.
ØBleeding that does not stop after a few minutes.
ØSevere fatigue.
Things you can do to lessen your risk of liver damage:
ØAvoid alcohol
ØLimit your use of acetaminophen
ØAvoid other medications that have caused liver dysfunction in the past.
ØCheck with your doctor or nurse before using any over-the-counter or alternative medications.
Lungs
Damage to the lungs is called pulmonary or lung toxicity. Lung toxicity may be short term or permanent. Damage to the lungs that resolves (returns to normal after time or after the cause has been removed) is called acute lung toxicity. Damage that is long lasting or permanent is called chronic or late pulmonary toxicity.
Two types of damage occur in lung toxicity; inflammation and fibrosis. Inflammation affects the cells that line the small sacs in the lungs that help with oxygen and carbon dioxide exchange. Inflammation of these small sacs makes the exchange of oxygen and carbon dioxide less efficient, decreasing the amount of oxygen that is absorbed and delivered to the body.
The second type of damage is fibrosis. This is the development of stiff, scar-like tissue in the lungs. Lung tissue is very elastic and it expands as you breathe to provide more space for air. Scarring reduces this elasticity and decreases the amount of air you can breathe in.
One of the ways that chemotherapy and radiation therapy kill cancer cells is by forming unstable molecules called free radicals. Free radicals are created during normal cellular processes that involve oxygen, such as burning fuel for energy. This free radical damage is worse in the lungs because of the high concentration of oxygen
Any chemotherapy can potentially damage the lungs; however, the most common chemotherapy drugs involved in causing lung toxicity are Bleomycin, Idarubicin and Arsenic Trioxide. Targeted agents like Tarceva can also cause lung damage. Patients receiving radiation therapy to the chest are at risk for developing lung toxicity, especially if they also receive chemotherapy. Symptoms of lung toxicity may occur early in the course of therapy or present 2 to 3 months after the beginning of treatment.
Risk factors for developing lung toxicity:
ØAge greater than 70 years.
ØPrior history of radiation therapy to the chest cavity.
ØThe total cumulative dose of certain chemotherapies (Bleomycin).
ØPre-existing lung disease.
ØReceiving combination therapy with more than one drug that has documented lung toxicity potential.
Lung toxicity is monitored by:
ØPhysical assessment. Your doctor will carefully listen to your lungs prior to the start of each treatment cycle and anytime you have any respiratory symptoms. We will also be monitoring the amount of oxygen in your blood by a test called Pulse Ox
ØWith certain therapies you will be required to do Pulmonary Functioning Testing (PFTs) prior to the start of that therapy and periodically throughout treatment.
ØYour doctor may request a chest x-ray prior to therapy to determine if you have any pre-existing problems.
Call your doctor if you experience any of the following:
ØBreathlessness during exercise.
ØDry cough.
ØNew onset of shortness of breath or worsening of already existing shortness of breath.
ØDiscomfort while lying on your back
There are things you can do to help manage the symptoms of lung toxicity:
ØTry relaxation techniques to control your breathing, such as meditation, yoga, or deep breathing exercises.
ØPromote oxygenation (air circulation) throughout your lungs, especially the bottom, to prevent infection and pneumonia. This can be done with breathing exercises or physical activity.
ØUse an incentive spirometer, a device that makes you breath slowly and deeply, to maintain oxygenation by helping to expand your lungs.
ØFind a kind of exercise that you can tolerate and do it daily.
ØAvoid smoking and smoke-filled environments. Smoking or second-hand smoke can further damage your lungs.
ØAvoid areas of pollution and poor air quality if you possibly can.
ØReduce anxiety and manage stress.