Reduced cardiotoxicity of doxorubicin by a 6-hour infusion regimen: a prospective randomized evaluation

Article Abstract:

Doxorubicin (Adriamycin) is an effective anti-cancer drug, but the dosage is limited by its cardiotoxicity (toxic effects to the heart). Although congestive heart failure is rare in patients with healthy hearts receiving less than a 400 milligrams per meter squared dose of doxorubicin, exceptions do occur. In addition, circumstances sometimes call for a greater dose, which necessitate the use of methods to reduce the risk of heart failure. It is generally thought that administering the drug over a six-hour period reduces the cardiotoxicity, but this has not been experimentally verified. To establish the effectiveness of the six-hour infusion of doxorubicin, 62 patients, 36 with metastatic breast cancer and 26 with advanced ovarian cancer, were randomly assigned to receive a six-hour infusion or the standard 15-to-20 minute infusion. Two independent methods were used to evaluate cardiac function before and after treatment. Radioactively labelled erythrocytes (red blood cells) were used to perform resting gated pool radionuclide angiography, a technique that permits the measurement of the left ventricle ejection fraction (percentage of blood emptied at the end of contraction). The height of the QRS complex (a specific wave pattern) on the electrocardiogram (ECG) was also measured. Four patients did not complete the chemotherapeutic regimen; cardiac function was normal in all four. In the remaining subjects, symptomatic congestive heart failure developed in four patients; all of these individuals were in the group receiving normal infusion. The measured left ventricle ejection fraction fell by a mean of 17 percent in the normal infusion group, but dropped only by four percent in the six-hour infusion group. Similarly, the height of the QRS complex fell by 29 percent in the rapid infusion group, but only by 1.5 percent in the six-hour infusion group. However, the reduction in QRS height did not correlate well with the change in left ventricle ejection fraction. This suggests that the ECG might not be an appropriate way of monitoring the cardiotoxicity of doxorubicin. In addition, there may be two types of cardiotoxicity occurring, one of which is more effectively measured by the ECG. Definite benefits were observed with the six-hour infusion treatment; the cardiotoxicity of doxorubicin seems to be related to the concentration of the drug, rather than to the total dose delivered. (Consumer Summary produced by Reliance Medical Information, Inc.)

Methods, Heart, Cancer, Dosage and administration

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Exercise echocardiography in the detection of anthracycline cardiotoxicity

Article Abstract:

Anthracyclines are a group of chemical substances which include some potent anticancer drugs. One such drug is doxorubicin. While these drugs are effective in improving survival in certain childhood and adult cancers, the toxic effects of these drugs are considerable, and there is much concern about long-term complications, such as damage to the heart. Little is known about the physical condition of patients who have been treated with anthracycline drugs but who do not have obvious heart damage. A study of 20 patients who had survived childhood cancers was undertaken to determine if the patients who received anthracyclines might have sustained subtle but detectable heart damage. Of the 20 study patients, 10 had received anthracyclines in the past and 10 had been treated with chemotherapeutic regimens that did not include such drugs. All 20 patients had normal heart function at rest. However, when the patients exercised, physiological measurements revealed signs of abnormal heart function that were not present at rest. Using echocardiography to image the beating heart, it was found that patients who had received anthracyclines did not develop as rapid blood flow through the aorta, the artery carrying blood from the heart to the body. Likewise, the contraction of the heart muscle fibers was not as robust in the patients who had received anthracycline drugs. However, it should be mentioned that these subtle differences in heart function did not prevent the patients who had received anthracyclines from performing just as much work as those who did not receive these drugs. Similarly, there were no significant differences between the two groups of patients in blood pressure or rate of the heart beat. These results suggest that many patients who received anthracyclines for cancer treatment have suffered subtle changes in heart function. These abnormalities are not apparent at rest but may become apparent with the added demands placed on the heart by exercise. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cancer in children, Childhood cancer, Anthracyclines

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Development of leukemia after doxorubicin and cisplatin treatment for ovarian cancer

Article Abstract:

Many studies have indicated that patients given chemotherapy are at increased risk for developing second, unrelated malignancies, usually taking the form of acute nonlymphocytic leukemia. Among patients with ovarian cancer, drugs which function as alkylating agents (work by chemically adding alkyl groups onto the structure of DNA) have been clearly shown to increase the risk of leukemia. However, two cases of ovarian cancer have been seen in which the patients developed leukemia or a pre-leukemia syndrome without prior exposure to alkylating agents. Both patients received treatment with cisplatin and doxorubicin. These drugs are not alkylating agents, although both have caused cancer in laboratory animals. One patient developed leukemia just over one year after beginning chemotherapy for ovarian adenocarcinoma. In addition to the standard cytologic analysis, a karyotype was performed and revealed chromosome rearrangements. Although treated with etoposide and cytosine arabinoside, her leukemia progressed and she died. At the time of her death, however, she was free of ovarian cancer. The second patient developed hematologic abnormalities suggestive of leukemia, which included chromosomal rearrangements. This woman died of her ovarian cancer without progression of the leukemia. The authors feel that the chromosome rearrangements which were observed may provide the key to determining if these leukemias may in fact be attributable to treatment with cisplatin and doxorubicin. (Consumer Summary produced by Reliance Medical Information, Inc.)

Case studies, Causes of, Ovarian cancer, Leukemia, Cisplatin

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