ISSN:
1569-8041
Keywords:
cardiac toxicity
;
endomyocardial biopsy scores
;
liposomal doxorubicin
;
MUGA scans
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Background:The indications for pegylated liposomal doxorubicin(doxil) are expanding. We, therefore, wished to assess the safety ofdelivering doses exceeding 500 mg/m2 of doxil to patients withsolid tumors. Patients and methods:Subjects accrued to eight phase I and IIprotocol studies conducted at two institutions, were assessed for cardiacfunction at baseline and at specified intervals by MUGA scans. In thisretrospective analysis, the findings of 42 patients, from the total of 237entered, who had reached or exceeded cumulative doses of 500 mg/m2(range 500–1500 mg/m2) were reviewed. Changes in leftventricular ejection fraction (LVEF), and in clinical cardiac status wereanalyzed. Six patients, three who had received prior doxorubicin, alsounderwent endomyocardial biopsies after cumulative doses of 490–1320mg/m2. Results:None of the 42 patients had clinical congestive heartfailure (CHF) secondary to cardiomyopathy. Post doxil MUGA scans wereavailable for 41 of the 42 patients. Five had a drop of 10% or more inLVEF; three of these had received prior doxorubicin. Billingham endomyocardialbiopsy scores ranged from 0–1 in five patients, while the sixth had ascore of 1.5 after both 900 mg/m2 and 1320 mg/m2 doxil.Of a remaining 195 patients, 1 episode of CHF was recorded in a patient whohad received 312 mg/m2 doxil over 120 mg/m2 ofmitoxantrone and chest radiation. Conclusions:Cumulative doses in excess of 500 mg/m2of doxil appear to carry a considerably lesser risk of cardiomyopathy asjudged by serial LVEF's and clinical follow-up, than is generally associatedwith free doxorubicin. Heart biopsies have provided reassuring data in a smallnumber of patients, even if pretreated with doxorubicin. However, since threedoxorubicin pretreated patients were among the five experiencing drops inLVEF, more data are warranted on such patients.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008365716693
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