A prospective randomized comparison of epirubicin and doxorubicin in patients with advanced breast cancer.

Jain, Krishan K.; Casper, Ephraim S.; Geller, Nancy L.; Hakes, T.; Kaufman, Richard J.; Currie, Violante E.; Schwartz, Walter; Cassidy, C; Petroni, Gina R.; Young, Charles W.

doi:10.1200/jco.1985.3.6.818

Cited by 238 publications

(77 citation statements)

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“…Epirubicin reportedly had lower cardiotoxicity compared with doxorubicin on the basis of a mg/m 2 cumulative dose. 13 In a large retrospective analysis, Ryberg et al reported estimated CHF risks of 0.6% and 14.5% at cumulative doxorubicin doses of 550 mg/m 2 and 1000 mg/m 2 , respectively. 14 However, a long-term prospective trial 15 showed that patients who received high cumulative doses of epirubicin (850 -1000 mg/m 2 ) had a risk of CHF that increased over a 5-year period (11% at 1 year, 20% at 5 years).…”

Section: Discussionmentioning

confidence: 99%

Congestive heart failure in patients treated with doxorubicin

Swain

Whaley²,

Ewer

2003

Cancer

1,954

1,256

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BACKGROUNDDoxorubicin is a highly effective and widely used cytotoxic agent with application that is limited by cardiotoxicity related to the cumulative dose of the drug. A large‐scale study that retrospectively evaluated the cardiotoxicity of doxorubicin reported that an estimated 7% of patients developed doxorubicin‐related congestive heart failure (CHF) after a cumulative dose of 550 mg/m2. To assess whether this estimate is reflective of the incidence in the broader clinical oncology setting, the authors evaluated data from three prospective studies to determine both the incidence of doxorubicin‐related CHF and the accumulated dose of doxorubicin at which CHF occurs.METHODSA group of 630 patients who were randomized to a doxorubicin‐plus‐placebo arm of three Phase III studies, two studies in patients with breast carcinoma and one study in patients with small cell lung carcinoma, were included in the analysis.RESULTSThirty‐two of 630 patients had a diagnosis of CHF. Analysis indicated that an estimated cumulative 26% of patients would experience doxorubicin‐related CHF at a cumulative dose of 550 mg/m2. Age appeared to be an important risk factor for doxorubicin‐related CHF after a cumulative dose of 400 mg/m2, with older patients (age > 65 years) showing a greater incidence of CHF compared with younger patients (age ≤ 65 years). In addition, > 50% of the patients who experienced doxorubicin‐related CHF had a reduction < 30% in left ventricular ejection fraction (LVEF) while they were on study.CONCLUSIONSDoxorubicin‐related CHF occurs with greater frequency and at a lower cumulative dose than previously reported. These findings further indicate that LVEF is not an accurate predictor of CHF in patients who receive doxorubicin. Cancer 2003;97:2869–79. © 2003 American Cancer Society.DOI 10.1002/cncr.11407

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Section: Discussionmentioning

confidence: 99%

Congestive heart failure in patients treated with doxorubicin

Swain

Whaley²,

Ewer

2003

Cancer

1,954

1,256

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“…Toxicity, however, was generally more pronounced in the doxorubicintreated patients. The four other studies compared the two drugs on an expected equimyelotoxic basis with doses of epirubicin ranging from 1.4 to 1.5 times the dose of doxorubicin (Jain et al, 1985;Taguchi et al, 1986;Hortobagyi et al, 1989;Perez et al, 1991). Similarly none of these studies showed significant differences in response rates, duration of response or survival between the two treatment arms.…”

Section: Discussionmentioning

confidence: 99%

Doxorubicin vs epirubicin, report of a second-line randomized phase II/III study in advanced breast cancer

et al. 1998

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Summary The EORTC Breast Cancer Cooperative Group carried out a randomized trial to compare doxorubicin with epirubicin as secondline chemotherapy in patients with metastatic breast cancer. Two hundred and fifty-nine patients with at least one site of metastatic disease entered this trial, of whom 232 patients were eligible. Treatment consisted of doxorubicin 75 mg m-2 or epirubicin 90 mg m-2 i.v. every 3 weeks. The overall response rates for doxorubicin and epirubicin were 36% and 28% respectively (P = 0.173). The median time to progression was 23 weeks for doxorubicin and 19 weeks for epirubicin (P = 0.063) and the median duration of response was 40 weeks for doxorubicin and 32 weeks for epirubicin (P = 0.059). The median survival was 47 weeks for doxorubicin and 44 weeks for epirubicin (P = 0.196). Leucocyte count on retreatment day (P = 0.011) and platelet nadir (P = 0.031) were significantly lower in the doxorubicin-treated group. Also mucositis (P < 0.001), diarrhoea (P = 0.005) and haemorrhage (P = 0.048) were significantly worse in the doxorubicin arm. Nine patients on doxorubicin and two patients on epirubicin experienced congestive heart failure (CHF). At the dose levels used in this study, no statistical differences in response rate and survival were found between the two treatment arms. Treatment with doxorubicin tended to result in a slightly longer duration of response and time to progression but doxorubicin was more toxic than epirubicin.

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“…As with doxorubicin, the incidence of epirubicin-induced cardiac failure is greatly dependent on the cumulative dose of epirubicin, but it depends also on other factors, such as the mode of administration of epirubicin, concomitant medication, presence of previous cardiac disease, amount of cardiac irradiation and individual and unrecognized factors. Congestive cardiac failure is rare at cumulative epirubicin doses less than 1000 mg m -2 in patients without known risk factors for cardiac failure (Jain et al, 1985;Dardir et al, 1989;Nielsen et al, 1990). However, no studies have yet addressed the clinical significance of subclinical cardiac damage, which may be a highly relevant issue in the long-term follow-up.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2000

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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...

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A prospective randomized comparison of epirubicin and doxorubicin in patients with advanced breast cancer.

Cited by 238 publications

References 17 publications

Congestive heart failure in patients treated with doxorubicin

Congestive heart failure in patients treated with doxorubicin

Doxorubicin vs epirubicin, report of a second-line randomized phase II/III study in advanced breast cancer

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

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