Seminars in oncology
-
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase of the ErbB family that is abnormally activated in many epithelial tumors. Several mechanisms lead to the receptor's aberrant activation that is observed in cancer, including receptor overexpression, mutation, ligand-dependent receptor dimerization, and ligand-independent activation. Two classes of anti-EGFR agents are currently approved for the treatment of patients with cancer: cetuximab, a monoclonal antibody directed at the extracellular domain of the receptor, and gefitinib and erlotinib, oral, low-molecular-weight (MW), adenosine triphosphate (ATP)-competitive inhibitors of the receptor's tyrosine kinase. ⋯ Clinical and survival benefits with anti-EGFR agents have been demonstrated in additional tumor types such as head and neck and pancreatic carcinomas. New agents with clinical activity are entering the clinic and new combinatorial approaches with anti-EGFR agents are being explored. Major efforts are, belatedly, attempting to identify molecular markers that can predict patients more likely to respond to anti-EGFR therapy.
-
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.
-
Seminars in oncology · Jun 2006
ReviewAnthracycline-induced cardiotoxicity in adult hematologic malignancies.
Anthracyclines are a highly efficacious treatment for adult hematologic malignancies, including acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, Hodgkin's disease, and non-Hodgkin's lymphoma. The consequences of anthracycline-induced cardiotoxicity have obliged hematologists to set empirical dose limits, above which the cardiotoxic risk is deemed unacceptable. ⋯ Through discontinuing further use of anthracyclines, relapsed patients previously treated with these agents may consequently be treated with second-line therapy that is less effective and possibly less well tolerated. Anthracycline-induced cardiotoxicity is potentially fatal and can significantly impair patients' quality of life, while also substantially increasing health care costs.
-
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.
-
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.