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document
Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma . BACKGROUND The objective of this study was to compare the efficacy and toxicity of the liposome-encapsulated doxorubicin , TLC D-99 ( Myocet , Elan Pharmaceuticals , Princeton , NJ ) , and conventional doxorubicin in first-line treatment of metastatic breast carcinoma ( MBC ) . METHODS Two hundred twenty-four patients with MBC and no prior therapy for metastatic disease were randomized to receive either TLC D-99 ( 75 mg/m ( 2 ) ) or doxorubicin ( 75 mg/m ( 2 ) ) every 3 weeks , in the absence of disease progression or unacceptable toxicity . The primary efficacy endpoint was response rate . Responses were assessed using World Health Organization criteria and were required to be of at least 6 weeks ' duration . The primary safety endpoint was cardiotoxicity . Cardiac function was monitored by multiple-gated radionuclide cardioangiography scan , and the left ventricular ejection fraction ( LVEF ) was scored at a central laboratory . Patients were removed from study if LVEF declined 20 or more EF units from baseline to a final value of greater than or equal to 50 % , or by 10 or more units to a final value of less than 50 % , or onset of clinical congestive heart failure ( CHF ) . RESULTS Median age was 54 years in both treatment groups . All relevant prognostic factors were balanced , with the exception that there were significantly more progesterone receptor positive patients in the doxorubicin-treated group . Protocol-defined cardiotoxicity was observed in 13 % of TLC D-99 patients ( including 2 cases of CHF ) compared to 29 % of doxorubicin patients ( including 9 cases of CHF ) . Median cumulative doxorubicin dose at onset of cardiotoxicity was 785 mg/m ( 2 ) for TLC D-99 versus 570 mg/m ( 2 ) for doxorubicin ( P = 0.0001 ; hazard ratio , 3.56 ) . The overall response rate was 26 % in both treatment groups . The median TTP was 2.9 months on TLC D-99 versus 3.1 months on doxorubicin . Median survival was 16 versus 20 months with a nonsignificant trend in favor of doxorubicin ( P = 0.09 ) . Clinical toxicities , commonly associated with doxorubicin , appeared less common with TLC D-99 , although the difference was not statistically significant . There was only one report of palmar-plantar erythrodysesthesia ( Grade 2 ) with this liposomal formulation of doxorubicin . CONCLUSIONS Single-agent TLC D-99 produces less cardiotoxicity than doxorubicin , while providing comparable antitumor activity .
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Intervention_Pharmacological
Liposome-encapsulated doxorubicin
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Intervention_Pharmacological
conventional doxorubicin
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Intervention_Pharmacological
liposome-encapsulated doxorubicin
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Intervention_Pharmacological
TLC D-99 ( Myocet , Elan Pharmaceuticals , Princeton , NJ )
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Intervention_Pharmacological
conventional doxorubicin
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Intervention_Pharmacological
TLC D-99 ( 75 mg/m ( 2 ) )
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Intervention_Pharmacological
doxorubicin
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Intervention_Other
multiple-gated radionuclide cardioangiography scan
7983
Intervention_Pharmacological
doxorubicin-treated
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Intervention_Pharmacological
doxorubicin
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Intervention_Pharmacological
doxorubicin
7986
Intervention_Pharmacological
TLC D-99
7987
Intervention_Pharmacological
doxorubicin
7988
Intervention_Pharmacological
doxorubicin
7989
Intervention_Pharmacological
doxorubicin
7990
Intervention_Pharmacological
doxorubicin
7991
Intervention_Pharmacological
TLC D-99
7992
Intervention_Pharmacological
doxorubicin
7993
Outcome_Other
Protocol-defined
7994
Outcome_Physical
cardiotoxicity
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Outcome_Other
Median cumulative doxorubicin dose at onset of
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Outcome_Physical
cardiotoxicity
7997
Outcome_Other
overall response rate
7998
Outcome_Other
median TTP
7999
Outcome_Mortality
Median survival
8000
Outcome_Adverse-effects
toxicities
8001
Outcome_Physical
palmar-plantar erythrodysesthesia
8002
Participant_Condition
metastatic breast carcinoma
8003
Participant_Sample-size
Two hundred twenty-four
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Participant_Condition
MBC
8005
Participant_Age
54 years