Pegylated liposomal doxorubicin (doxil): Reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m(2)

Background: The indications for pegylated liposomal doxorubicin (doxil) are expanding. We, therefore, wished to assess the safety of delivering doses exceeding 500 mg/m(2) of doxil to patients with solid tumors. Patients and methods: Subjects accrued to eight phase I and II protocol stu dies conducted at two institutions, were assessed for cardiac function at b aseline and at specified intervals by MUGA scans. In this retrospective ana lysis, the findings of 42 patients, from the total of 237 entered, who had reached or exceeded cumulative doses of 500 mg/m(2) (range 500-1500 mg/m(2) ) were reviewed. Changes in left ventricular ejection fraction (LVEF), and in clinical cardiac status were analyzed. Six patients, three who had recei ved prior doxorubicin, also underwent endomyocardial biopsies after cumulat ive doses of 490-1320 mg/m(2). Results: None of the 42 patients had clinical congestive heart failure (CHF ) secondary to cardiomyopathy. Post doxil MUGA scans were available for 41 of the 42 patients. Five had a drop of 10% or more in LVEF; three of these had received prior doxorubicin. Billingham endomyocardial biopsy scores ran ged from 0-1 in five patients, while the sixth had a score of 1.5 after bot h 900 mg/m(2) and 1320 mg/m(2) doxil. Of a remaining 195 patients, 1 episod e of CHF was recorded in a patient who had received 312 mg/m(2) doxil over 120 mg/m(2) of mitoxantrone and chest radiation. Conclusions: Cumulative doses in excess of 500 mg/m(2) of doxil appear to c arry a considerably lesser risk of cardiomyopathy as judged by serial LVEF' s and clinical follow-up, than is generally associated with free doxorubici n. Heart biopsies have provided reassuring data in a small number of patien ts, even if pretreated with doxorubicin. However, since three doxorubicin p retreated patients were among the five experiencing drops in LVEF, more dat a are warranted on such patients.