PMID- 11038041
OWN - NLM
STAT- MEDLINE
DCOM- 20010201
LR  - 20220330
IS  - 0923-7534 (Print)
IS  - 0923-7534 (Linking)
VI  - 11
IP  - 8
DP  - 2000 Aug
TI  - Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in 
      patients reaching or exceeding cumulative doses of 500 mg/m2.
PG  - 1029-33
AB  - BACKGROUND: The indications for pegylated liposomal doxorubicin (doxil) are 
      expanding. We, therefore, wished to assess the safety of delivering doses 
      exceeding 500 mg/m2 of doxil to patients with solid tumors. PATIENTS AND METHODS: 
      Subjects accrued to eight phase I and II protocol studies conducted at two 
      institutions, were assessed for cardiac function at baseline and at specified 
      intervals by MUGA scans. In this retrospective analysis, the findings of 42 
      patients, from the total of 237 entered, who had reached or exceeded cumulative 
      doses of 500 mg/m2 (range 500-1500 mg/m2) were reviewed. Changes in left 
      ventricular ejection fraction (LVEF), and in clinical cardiac status were 
      analyzed. Six patients, three who had received prior doxorubicin, also underwent 
      endomyocardial biopsies after cumulative doses of 490-1320 mg/m2. 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 ranged from 0-1 in five 
      patients, while the sixth had a score 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 
      who had received 312 mg/m2 doxil over 120 mg/m2 of mitoxantrone and chest 
      radiation. CONCLUSIONS: Cumulative doses in excess of 500 mg/m2 of doxil appear 
      to carry a considerably lesser risk of cardiomyopathy as judged by serial LVEF's 
      and clinical follow-up, than is generally associated with free doxorubicin. Heart 
      biopsies have provided reassuring data in a small number of patients, even if 
      pretreated with doxorubicin. However, since three doxorubicin pretreated patients 
      were among the five experiencing drops in LVEF, more data are warranted on such 
      patients.
FAU - Safra, T
AU  - Safra T
AD  - USC/Norris Comprehensive Cancer Center, University of Southern California, Los 
      Angeles, USA.
FAU - Muggia, F
AU  - Muggia F
FAU - Jeffers, S
AU  - Jeffers S
FAU - Tsao-Wei, D D
AU  - Tsao-Wei DD
FAU - Groshen, S
AU  - Groshen S
FAU - Lyass, O
AU  - Lyass O
FAU - Henderson, R
AU  - Henderson R
FAU - Berry, G
AU  - Berry G
FAU - Gabizon, A
AU  - Gabizon A
LA  - eng
GR  - P30 CA 14089/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Liposomes)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/administration & dosage/*adverse effects
MH  - Cardiomyopathies/chemically induced/complications/*prevention & control
MH  - Doxorubicin/administration & dosage/*adverse effects
MH  - Female
MH  - Heart Failure/etiology/*prevention & control
MH  - Humans
MH  - Liposomes
MH  - Male
MH  - Middle Aged
MH  - Retrospective Studies
EDAT- 2000/10/19 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/19 11:00
PHST- 2000/10/19 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/19 11:00 [entrez]
AID - S0923-7534(19)55632-0 [pii]
AID - 10.1023/a:1008365716693 [doi]
PST - ppublish
SO  - Ann Oncol. 2000 Aug;11(8):1029-33. doi: 10.1023/a:1008365716693.