Cardiotoxicity from intensive chemotherapy combined with radiotherapy in breast cancer

Graaf, Hiltje de; Dolsma, W.V.; Willemse, Pax H.B.; Graaf, Winette T.A. van der; Sleijfer, Dt; Vries, Elisabeth G.E. de; Mulder, Nh

doi:10.1038/bjc.1997.489

Cited by 22 publications

(12 citation statements)

References 21 publications

(15 reference statements)

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“…The alterations of the functional parameters caused by DOX are similar to those observed in bioptic fragments of humans [Levey et al, 1979;Ganz et al, 1996;Postma et al, 1996;de Graaf et al, 1997] and rats [Iliskovic et al, 1997]. These results are also similar to the observations of other workers [Mimnaugh et al, 1983;Luo et al, 1997;Morishima et al, 1998Morishima et al, , 1999.…”

Section: Discussionsupporting

confidence: 89%

Melatonin protects against cardiac toxicity of doxorubicin in rat

Qian

et al. 2001

Journal of Pineal Research

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Doxorubicin (DOX) is commonly used for the treatment of hematological and solid tumors. However, there are serious toxic effects on the cardiovascular system, which limits the application of the drug. Recently, melatonin has been reported to have immunomodulatory effect in addition to lowering cholesterol levels as well as inhibiting malignant tumors. In this study, the effect of melatonin against the toxicity of doxorubicin was investigated in rats. Hemodynamic function, pathological and biochemical changes were determined in different treated hearts. Our findings showed that a significant protection by melatonin (6 mg kg−1 for 15 days, cumulative dose of 90 mg kg−1) against the DOX‐induced toxicity was observed. Cardiac function was improved and lipid peroxidation decreased after melatonin treatment. It is concluded that melatonin provides protection against doxorubicin toxicity via an attenuation of lipid peroxidation.

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Section: Discussionsupporting

confidence: 89%

Melatonin protects against cardiac toxicity of doxorubicin in rat

Qian

et al. 2001

Journal of Pineal Research

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“…It has been associated with the use of anthracyclines or radiotherapy and when both treatment modalities have been combined, the risk of cardiac toxicity has been enhanced [1,7]. However, most studies included patients who received chemotherapy and radiotherapy and, for this reason, it is very difficult to define the role of anthracyclines in cardiac toxicity.…”

Section: Discussionmentioning

confidence: 95%

Late cardiac toxicity secondary to treatment in Hodgkin's disease. A study comparing doxorubicin, epirubicin and mitoxantrone in combined therapy

Avilés

Neri

Nambo

et al. 2005

Leukemia & Lymphoma

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Anthracyclines are a group of drugs that are useful in the treatment of Hodgkin's disease, but have been associated with severe, and in some cases lethal, cardiac toxicity. Apparently, cardiac toxicity is more frequent after 10 years of anthracycline therapy, but no longer studies of cardiac toxicity have been reported. Four hundred and seventy-six patients with Hodgkin's disease, stages III and IV, were randomly assigned to receive ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) compared with EBVD (epirubicin instead of doxorubicin) and MBVD (mitoxantrone instead of doxorubicin) at standard doses. The endpoint was the presence of a clinical cardiac event (CCE) or abnormalities in equilibrium radionuclide angiocardiography (ERNA) and echocardiogram. The patients did not receive radiation therapy and when relapsed they were censored from cardiac toxicity. The median follow-up was 11.5 years (range 7.5 - 14.8 years). CCE was observed in 17% in the MBVD arm, 9% in the ABVD arm and 6% in the EBVD arm (P < 0.001). Mortality associated with CCE was 12% with MBVD, 7% with ABVD and 2% with EBVD. Abnormalities in ERNA and echocardiogram were observed 6 - 36 months before the presence of a CCE. An excess in the standard mortality ratio was observed with the 3 regimens when compared with the general population: 19.4 for EBVD, 46.0 for ABVD and 67.8 for MBVD, which was confirmed with an increase in absolute excess risk/10,000 person-years of 15.6, 39.0 and 58.7, respectively. Overall survival was better in patients treated with EBVD because less cardiac events were observed. The use of mitoxantrone was associated with a high rate of relapse and cardiac events. Thus, we would not recommend use of the drug in Hodgkin's disease. ERNA and echocardiogram are early detection tests for cardiac toxicity and can be employed in surveillance studies.

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“…de Graaf et al 18 reported 86 patients with locally advanced or metastatic breast cancer treated with doxorubicin or epirubicin-based induction chemotherapy and cyclophosphamide or mitoxantrone-based ablative chemotherapy. All patients had normal cardiac function before starting treatment.…”

Section: Bone Marrow Transplantationmentioning

confidence: 99%

The feasibility of high-dose chemotherapy in breast cancer patients with impaired left ventricular function

Rose

Gollerkeri

et al. 2000

Bone Marrow Transplant

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Summary:Breast cancer patients with cardiac disease are usually excluded from clinical trials of high-dose chemotherapy. We treated 52 patients with inflammatory and/or metastatic disease with sequential high-dose melphalan and stem cell rescue followed by high-dose thiotepa and stem cell rescue. Stem cells were mobilized with cyclophosphamide and/or paclitaxel and filgrastim. Left ventricular ejection fraction (LVEF) was measured by equilibrium radionuclide angiocardiography (ERNA) at baseline, after each course of chemotherapy and 4 weeks after completing both transplants. The mean absolute decrease in LVEF after the two transplants was 3.6% (P ‫؍‬ 0.008 for the comparison with baseline LVEF), and most of this drop (؊2.5%, P ‫؍‬ 0.007) occurred after mobilization. Unexpectedly, paclitaxel was associated with a mean absolute decrease in LVEF of 3.4% (P ‫؍‬ 0.032, n ‫؍‬ 19), cyclophosphamide alone was not associated with a significant change in LVEF (؊1.3%, P ‫؍‬ 0.23), but mobilization with sequential paclitaxel and cyclophosphamide resulted in a mean absolute drop of 4.9% in LVEF (P ‫؍‬ 0.009). Twelve patients were found to have a reduced LVEF (Ͻ50%) at least once during treatment and had a mean absolute decrease in LVEF of 10% (P ‫؍‬ 0.008) from baseline, compared with a drop of only 1.8% (P ‫؍‬ 0.176) in the patients without impaired LV function. Although two of these 12 patients developed symptomatic heart failure, their cardiac symptoms were easily treated and there were no cardiac deaths. We conclude that our protocol has acceptable cardiac toxicity and breast cancer patients with impaired LV function should not be denied high-dose chemotherapy if otherwise indicated. Bone Marrow Transplantation (2000) 26, 133-139.

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Cardiotoxicity from intensive chemotherapy combined with radiotherapy in breast cancer

Cited by 22 publications

References 21 publications

Melatonin protects against cardiac toxicity of doxorubicin in rat

Melatonin protects against cardiac toxicity of doxorubicin in rat

Late cardiac toxicity secondary to treatment in Hodgkin's disease. A study comparing doxorubicin, epirubicin and mitoxantrone in combined therapy

The feasibility of high-dose chemotherapy in breast cancer patients with impaired left ventricular function

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