Subclinical cardiotoxicity following adjuvant dose-escalated FEC, high-dose chemotherapy, or CMF in breast cancer

Abstract

Anthracyclines are used extensively in therapy of several types of human cancer where long-term survival and cure are common, such as haematological malignancies and paediatric cancers. They are now increasingly used also in adjuvant therapy of breast cancer, because the results of some trials suggest that anthracycline-containing combinations are associated with better survival than non-anthracycline-containing regimens (Early Breast Cancer Trialists' Collaborative Group, 1998). These trials have, however, only limited follow-up of a few years. Cardiotoxicity is a wellestablished side-effect of anthracyclines, and subclinical cardiotoxicity of adjuvant and other curative therapies might manifest only several decades after treatment when the myocardial reserves start to decrease in old age. This might counterbalance the shortterm absolute survival benefit associated with anthracyclinecontaining regimens over CMF (cyclophosphamide, 5-fluorouracil and methotrexate), which is only about 3% at 5 years of follow-up according to the meta-analysis (Early Breast Cancer Trialists' Collaborative Group, 1998). Cardiotoxicity of anthracyclines may be reduced by low-peak therapies, such as anthracyclines given as long infusions (Legha et al, 1982). A novel iron-chelating agent, dexrazoxane, has reduced anthracycline-associated cardiotoxity in several randomized trials, and apart from one study, it has not reduced response rates (Green, 1998).High-dose chemotherapy is used increasingly in therapy of breast cancer both in the US and Europe (Antman et al, 1997;Grathwohl et al, 1997). In the USA, breast cancer is the most common indication for high-dose chemotherapy given with the support of either bone marrow or peripheral blood stem cell rescue at present (Antman et al, 1997). It is currently highly controversial whether high-dose chemotherapy is superior to conventional-dose chemotherapy either in the adjuvant or the metastatic setting, but several controlled trials are currently in progress to resolve the issue. Favourable results have been obtained with adjuvant highdose therapy in phase II studies (Peters, 1996), and many breast cancer patients with a high risk of relapse are now given high-dose therapy. However, besides its efficacy, the long-term risks of highdose therapy are unsettled. Little is known about the subclinical cardiac toxicity related to high-dose adjuvant therapy, which might be of great importance for the long-term survivors from cancer.Endomyocardial biopsy is the most reliable method to diagnose anthracycline-induced cardiotoxicity. However, a non-invasive method of indium-111 monoclonal antimyosin antibody scintigraphy has been shown to be highly sensitive for detecting cardiac damage. The method is capable for detecting even small areas of myocardial damage or necrosis in a variety of diseases Verna et al, 1995;Astorri et al, 1996;Ballester et al, 1997aBallester et al, , 1997bBengel et al, 1997; Schutz et al, 1997). Moreover, it may be the only non-invasive method currently available for detection o...

Combination chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil causes trabecular bone loss, bone marrow cell depletion and marrow adiposity in female rats

“…Anthracyclines are now classified as the central components of most breast cancer regimens, as they can be used for adjuvant therapy regardless of the nodal involvement, hormone receptor status or the expression levels of human epidermal growth factor receptor 2 (HER-2) of the tumour [2]. While some previous studies have described CEFrelated adverse effects being mainly related to haematological and cardiac toxicity [27][28][29], no studies to date have reported the potential adverse effects of CEF treatment on bone health, although potential direct and indirect bone effects of these drugs individually have been reported previously. For example, a single high-dose injection of 5-FU in young rats was shown to induce severe trabecular bone loss due to enhanced resorption [12].…”

Cardiac toxicity of high-dose chemotherapy

“…The scan was negative in 14/14 patients treated with the HD cyclophosphamidecontaining regimen STAMP-V (cyclophosphamide, thiotepa and carboplatin). 120 Natriuretic peptides (atrial natriuretic peptide, ANP and brain natriuretic peptide, BNP) are cardiac hormones released in response to atrial or ventricular load-induced stresses, and their plasma levels are inversely correlated with measures of cardiac function. 121 Existing data suggest a strong correlation between natriuretic peptide measurement and myocardial dysfunction following standard dose anthracycline chemotherapy.…”

Impact of Mindfulness-Based Stress Reduction (MBSR) on attention, rumination and resting blood pressure in women with cancer: A waitlist-controlled study

“…Despite recent medical advances, acute stress at the time of cancer diagnosis (Zabora et al, 2001) and chronic stress thereafter (Carlson et al, 2004) is common and is associated with anxiety, depression (Kissane et al, 2004), fatigue (Carlson et al, 2004), and sleep problems (Fortner et al, 2002). In addition to being at risk for emotional and physical symptoms, cancer patients are at significant risk for cardiac toxicity and damage as a result of primary treatments (i.e., chemotherapy and radiation) (Benvenuto et al, 2003;Erselcan et al, 2000;Meinardi et al, 2000;Meinardi et al, 2001;Vallebona, 2000). Cardiovascular side effects of primary cancer treatments may have a dramatic impact on quality of life and patient survival (Benvenuto et al, 2003).…”