Prospective study of left ventricular function using radionuclide scans in patients receiving mitoxantrone

A prospective Phase II study to evaluate the effects of mitoxantrone on left ventricular ejection fraction (LVEF) has been carried out in patients treated with 12 mg/m2 every three weeks. Gated radionuclide cardiac blood pool imaging with assessment of LVEF and wall motion prior to and during graded exercise was performed before the first and every other mitoxantrone course. Ten patients had either a minor response or tumour stabilization while receiving mitoxantrone treatment and underwent serial radionuclide scans during the course of therapy. Three patients who had received adriamycin as part of prior chemotherapy regimens showed no evidence of cardiotoxicity. Seven patients, who had had no prior adriamycin exposure, underwent serial radionuclide studies while receiving up to 204 mg/m2 of mitoxantrone. None of these patients showed evidence of clinically significant myocardial damage. One had a decline in LVEF from 70% to 50% at a maximum dose of 108 mg/m2. An additional patient whose LVEF rose from 57% at baseline to 62% at a total dose of 204 mg/m2 (17 courses) underwent endomyocardial biopsy which showed grade 2.5 anthracyclin-type cardiotoxicity. Serial endomyocardial biopsy studies are indicated in patients on longterm drug therapy to determine the incidence, dose-relationship and severity of potential mitoxantrone associated endomyocardial damage.