Systolic time interval as index of schedule--dependent doxorubicin cardiotoxicity in patients with acute myelogenous leukaemia

Abstract

The ratio of the pre-ejection period to the left ventricular ejection time (PEP:LVET) was measured in two groups of patients with acute myeloblastic leukaemia (AML) receiving the anthracycline antibiotic doxorubicin (DXR). Patients receiving high doses of DXR per course (about 90 mg/m2) showed a significant increase in the PEP:LVET ratio irrespective of the total cumulative dose. At a lower dose per course (less than 50mg/m2) only patients who had a total cumulative dose of over 450 mg/m2 showed significant increases in ratio. ECG changes were seen in both groups of patients but did not correlate significantly with the dosage. These findings, which suggest that DXR cardiotoxicity is schedule dependent, are important in the design of schedules of DXR for treating cancer and in interpreting the changes in systolic time intervals (STIs) observed with different schedules. Measurement of the STI is a simple and convenient method of assessing DXR cardiotoxicity. While a total DXR dose of 550 mg/m2 should not normally be exceeded, by carefully monitoring the STI the recommended total dose may be exceeded safely in selected patients.