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Life After Cancer A Roadmap for Cancer Survivors

Cancer Treatment Side Effects and Solutions
Ernest H. Rosenbaum, MD

Chemotherapy-related Cardiac Toxicity
Radiation Therapy-related Cardiac and Pulmonary Toxicity
Prevention of Cardiopulmonary Side Effects
Renal (Kidney) Toxicity Side Effects
The Need for Long-term Surveillance

Chemotherapy-related Cardiac Toxicity
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There are many drugs that cause cardiac toxicity. Cardiomyopathy (heart muscle damage and weakness affecting ventricular systole function, diastolic function, or both) is most commonly caused by the anthracycline Adriamycin, trastuzumab (Herceptin), and is sometimes caused by high dose cyclophosphamide (Cytoxan). Paclitaxel (Taxol is associated with arrhythmias (irregular heart beat) or bradycardia (slow heart rate). Rarely, 5FU can also cause arrhythmia. Trastuzumab (Herceptin) has shown the possibility of causing congestive heart failure in patients who have had Hodgkin's disease (mantle chest wall radiation) or left chest wall radiotherapy for breast cancer, who have pre-existing heart disease or other cardiac risk factors, or who have received drugs that could have additive or synergistic effects (such as cyclophosphamide [cytoxan] or adriamycin).

Using anthracycline analogs, such as epirubicin (Ellence®) as a substitute for adriamycin (i.e. CEF- cytoxan/epirubicin/5FU) produces less cardiotoxicity. Other alternatives to reduce toxicity include dose schedules, using intravenous adriamycin infusions, and selective delivery systems, or using liposomes, such as Doxil® (adriamycin in lipid capsules). In addition, dexrazoxane (Zinecard) can help reduce cardiac toxicity in adult breast cancer patients, but was associated with a reduction of response rate in a study. Zinecard was also associated with reduced cardiotoxicity but increased second malignancy in pediatric cancer patients.

Potential complicating heart toxic factors
- Smoking
- Prior left-sided heart irradiation, for a left breast cancer, Hodgkin's or Non-Hodgkin's disease treatments
- High blood pressure (hypertension) is associated with heart disease, because of stress on the heart with hypertension.
- Diabetes
- A baseline low normal heart left ventricle ejection fraction (LVEF) had a much higher incidence of heart failure 14.5%, compared to those who had a normal cardiac ejection fraction.
- Patients over 50 years of age who had a low normal ejection fraction.
- Use of docetaxel (Taxotere®), cyclophosphamide, or a taxane/carboplatin or possibly a hormonal therapy alone. (This approach is being tested in the metastatic setting). Infusions on weekly schedules could be used or liposomal adriamycin (Doxil®) as a possible substitution for an anthracycline (adriamycin).

Radiation Therapy-related Cardiac and Pulmonary Toxicity
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The overview data on mastectomy followed by left chest wall radiation shows an increased incidence of mortality related to cardiovascular events, but recent data for breast conserving therapy with improved radiation treatment planning had lower all-cause mortality at the 15 year follow-up. There is not an increase in cardiac events with newer modern chest wall irradiation technology.

Cardiac toxicity may also result from chest irradiation for Hodgkin's disease and Non-Hodgkin's lymphoma. This is a potential problem in children and adults and may involve coronary blood vessels, heart muscle tissue, pericardium (the sac covering the heart), and heart valves. This risk has been reduced with newer modern chest wall irradiation technology as well as modifications in chemotherapy.

Pulmonary lung toxicity such as pneumonitis and fibrosis (scarring) can be a result of radiation alone. This depends on the volume of irradiated lung and the dose and the daily radiation fractionation used. Radiation destroys cells lining the alveoli (lung air sacks at the end of the bronchioli where oxygen and carbon dioxide are exchanged) causing the alveoli to become inflamed, accumulating fluid. This affects the passage of oxygen and carbon dioxide within the alveoli to the blood vessels.

When treatment combines chemotherapy and radiation therapy, the risk of cardiopulmonary toxicities is increased.

The pulmonary toxicity following therapy with either bleomycin or radiation is increased in cigarette smokers. The lungs can be affected by radiation to the chest and also by treatment with bleomycin. Radiation has long-term side effects on other organs and tissues.

Bleomycin has been used in combination chemotherapy for patients with germ cell tumors, Hodgkin's disease and non-Hodgkin lymphoma for more than 20 years. Following treatment with bleomycin, caution needs to be observed with the use of oxygen for pulmonary insufficiency (shortness of breath). Oxygen should not be denied if hypoxic (shortness of breath occurs).

Bleomycin risk factors that have been associated with pulmonary toxicity are age >40 years, cumulative dose >450 units, renal failure, concomitant administration of cisplatin, cyclophosphamide, methotrexate and doxorubicin, chest irradiation and positive fluid balance during prolonged surgical procedures. Pulmonary consultation is mandatory before surgery for patients who have received bleomycin. Lung problems can occur months or years after treatments. Drugs such as digoxin or Dilantin may have an interaction with bleomycin.

The oxygen concentration (FIO2) during and after surgery should be kept as low as possible and fluid status should be closely monitored by the anesthesiologists.

If supplemental oxygen is required, use the lowest FIO2 that maintains adequate tissue oxygenation. Recreational use of high flow oxygen (e.g., scuba diving) should be discouraged. Carry a Medical Emergency Information - A Simple Card or Medical ID alert wrist bracelet listing potential bleomycin sensitivity.

Prevention of Cardiopulmonary Side Effects
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There have been long-term survivors from many cancers (such as breast cancer, testicular cancer, Hodgkin's and non-Hodgkin's lymphoma) who have developed long-term cardiopulmonary toxicity due to cancer therapies.

Fortunately, with the continuing advances in computerized radiotherapy treatment planning (CAT scans), the risk of radiation heart damage has been minimized.

Potential toxicity: If symptoms such as shortness of breath, chest heaviness or pain and rapid heart beat are present, a cardiopulmonary evaluation by a cardiologist or pulmonary specialist is mandatory. Other indicators include swelling of the legs (from heart failure or possibly blood clots which could lead to pulmonary embolus [a blood clot from the legs which travels to the lungs]), fatigue, tiredness, and a low-grade fever.

Breathing problems (shortness of breath on exertion) require a pulmonary function analysis. Treatment with medications and inhalers can help relieve symptoms. A pulmonary rehabilitation program also can be helpful to strengthen the body and to teach survivors techniques for better breathing and lung physiology.

Renal (Kidney) Toxicity Side Effects
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Patients treated with radiation therapy that included the kidneys, or who received chemotherapy with any of the platinum compounds are at risk for kidney problems and possibly kidney failure. Platinum compounds (cis-platinum and carboplatin) can also result in some hearing loss, especially for high frequency sounds, rather than those in the speech range. Amifostine (Ethyol®) has been effective in reducing platinum kidney toxicity.

Abdominal radiation can cause intestinal adhesions, malabsorption, chronic diarrhea, lactose intolerance, and subsequent discomfort and weight loss.

A full evaluation including chest x-ray, electrocardiogram, echocardiogram, and physical examination are part of the standard assessment for kidney toxicity.

The Need for Long-term Surveillance
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Following the completion of cancer therapy, patients who have received radiation or cardiopulmonary toxic chemotherapy drugs merit long-term follow-up. Left heart ventricular systolic ejection time less than 45%, or a decrease of 5% or more from the resting level, is abnormal and merits careful assessment.

Cardio/pulmonary evaluations include a cardio/pulmonary consultation, EKG, echocardiogram, chest x-ray, CAT scans of the chest, and pulmonary function tests to assess for any pulmonary toxicity. Careful follow-up is recommended.

The treatment plan may require a cardiac and/or pulmonary consultation. Often oxygen combined with a special cardio/pulmonary medication program can be very helpful in reducing cardiac or pulmonary symptoms.

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First appeared December 30, 2007; updated August 2, 2008