Detection of Doxorubicin Cardiotoxicity in Patients with Sarcomas by Indium-111-antimyosin Monoclonal Antibody Studies

To assess myocardial cell damage due to doxorubicin cardiotoxicity, we prospectively studied 30 patients with sarcomas who were receiving chemotherapy, including doxorubicin. Sixteen patients were treated by continuous infusion over 72 hr and 14 patients were treated by bolus injection. Antimyosin studies and left ventricular ejection fraction (LVEF) measurements were performed before chemotherapy and at intermediate and maximal cumulative doses. Myocardial antimyosin uptake was quantified by a heart-to-lung ratio (HLR). Myocardial antimyosin uptake was observed in all patients at 240-300 mg/m2 when ejection fraction was still maintained. Seven patients presented with a decrease of > or = 10% in absolute ejection fraction units at 420-600 mg/m2. Five of these patients had mild congestive heart failure. All patients who presented with a decrease in LVEF > or = 10% at 420-600 mg/m2 had increased antimyosin uptake with HLR > or = 1.90 at a cumulative dose of 240-300 mg/m2. Patients who were treated with continuous infusion had less antimyosin uptake than those who were treated with bolus administration (mean HLR of 1.70 +/- 0.09 versus HLR of 2.01 +/- 0.16 at a cumulative dose of 240-300 mg/m2, p < 0.01; HLR of 1.86 +/- 0.12 versus HLR of 2.32 +/- 0.34 at a cumulative dose of 420-600 mg/m2, p < 0.01). Two of 16 patients treated by continuous infusion and 5 of 14 patients treated by bolus injection presented with a decrease in ejection fraction > or = 10%. LVEF after chemotherapy in the infusion group was 56% +/- 5% and 48% +/- 8% (p < 0.05) in the bolus group. Antimyosin studies are helpful in the assessment of doxorubicin cardiotoxicity. Intense antimyosin uptake at intermediate cumulative doses identifies patients at risk of cardiotoxicity before ejection fraction deteriorates. Patients with sarcomas treated by continuous infusion present with less antimyosin uptake than those treated with bolus injection, indicating less severe cardiotoxicity.