Seminars in oncology
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Anthracyclines are potent anti-neoplastic drugs used in the treatment of solid and hematologic cancers. However, their use is limited by cumulative dose-related cardiotoxic adverse effects, which are progressive and irreversible from the first dose. Clinical trial data have shown that anthracycline cardiotoxicity is associated with slowly progressive deterioration of cardiac function, which continues for years after treatment cessation. ⋯ The widespread use of anthracyclines in childhood leukemia has resulted in an improved long-term prognosis; however, these patients are subsequently at high risk of developing long-term cardiac damage, with studies suggesting as many as 65% of survivors of childhood leukemia will develop cardiac abnormalities. Middle aged and elderly patients who are prone to cardiac disease may be more vulnerable to the cardiotoxic effects of anthracyclines. Therapies or strategies to prevent anthracycline-induced cardiotoxicity are essential; ideally, these should be initiated at the beginning of anthracycline therapy to reduce the possibility of cardiac damage and to ensure the optimal use of chemotherapy.
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Seminars in oncology · Jun 2006
ReviewExposure to anthracyclines during childhood causes cardiac injury.
The use of anthracyclines in the treatment of acute lymphoblastic leukemia is limited by associated cardiotoxic effects, which can result in cardiomyopathy and congestive heart failure, and may be irreversible. Anthracycline-induced cardiotoxicity in long-term survivors of childhood cancer is characterized by reduced left ventricular wall thickness and mass, which is indicative of decreased cardiac muscle and depressed left ventricular contractility which is indicative of unhealthy heart muscle. Risk factors for anthracycline-induced cardiotoxicity include high cumulative anthracycline doses, high anthracycline dose intensity, and radiotherapy. ⋯ There is evidence that dexrazoxane significantly reduces the cardiotoxicity associated with anthracyclines such as daunorubicin, doxorubicin, and epirubicin in adult patients with a wide range of tumor types. A study of the efficacy of dexrazoxane in reducing doxorubicin-induced cardiotoxicity in children and adolescents with high-risk acute lymphoblastic leukemia, showed that significantly fewer dexrazoxane-treated patients (21%) had elevated serum cardiac troponin (a biomarker of acute myocardial injury) levels than patients treated with chemotherapy alone (50%; P <.001). Dexrazoxane was also shown to have no effect on the event-free survival rate at 2.5 years, emphasizing that it does not detrimentally affect the efficacy of anthracycline therapy.
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Neurotoxicity related to cancer therapy is a common problem in oncology practice. Neurologic side effects can be dose-limiting, can inhibit treatment, and can substantially diminish quality of life. ⋯ When faced with the development of neurologic complaints, familiarity with the most common complications is helpful in determining the etiology of these symptoms. This review will discuss the common complications of both established and novel agents used to treat cancer.
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Seminars in oncology · Jun 2006
ReviewCardiotoxic consequences of anthracycline-containing therapy in patients with breast cancer.
In women, breast cancer is the second most common form of cancer and the leading cause of death caused by malignancy. The anthracycline antibiotics are potent anti-tumor agents used in a wide spectrum of malignancies. They are part of the gold standard adjuvant therapy for breast cancer and in metastatic disease they provide significant increases in response rate, time to disease progression, and overall survival. ⋯ The onset of clinical and subclinical cardiac damage is delayed and occurs more than 3 months after the cessation of treatment, indicating a crucial time for functional impairment to occur and highlighting the ineffectiveness of monitoring left ventricular ejection fraction as an endpoint during anthracycline therapy. Possible future treatment options for managing anthracycline-induced cardiotoxicity include agents such as dexrazoxane that prevent oxygen-free radical generation. Further investigation is required into the use of angiotensin-converting enzyme inhibitors to redress cardiac damage and new methods of identifying patients at high risk of congestive heart failure before cardiac damage has occurred.
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The majority of patients with ovarian cancer will relapse despite state-of-the-art first-line surgery and chemotherapy. There are two subgroups of patients with recurrent ovarian cancer: those with platinum-resistant disease and those with platinum-sensitive disease. Re-treatment with single-agent platinum has long been considered standard therapy for patients with platinum-sensitive disease, and, based on its favorable therapeutic profile, carboplatin has become the treatment agent of choice. ⋯ The toxicity profiles and schedules of carboplatin plus paclitaxel and carboplatin plus gemcitabine are different, with the taxane combination having greater neurotoxicity and alopecia, less hematologic toxicity, and requiring longer drug infusions (although fewer days of treatment per cycle) than the gemcitabine combination. Based on the results of these two trials, combination chemotherapy should be considered the standard treatment of recurrent platinum-sensitive ovarian cancer. The choice of treatment needs to take into account the increase in side effects when using combination chemotherapy compared with carboplatin monotherapy, and the different toxicities of the two combination regimens.