Liposomal-encapsulated doxorubicin plus cyclophosphamide as first-line therapy in metastatic breast cancer: a phase II multicentric study.

BACKGROUND: The objective of this study is to evaluate the efficacy and toxicity of the liposome-encapsulated doxorubicin (TLC D-99) plus cyclophosphamide (CTX) as first-line treatment of metastatic breast cancer in light of the potential cardioprotective effect of TLC D-99 as compared with conventional doxorubicin. MATERIALS AND METHODS: Sixty-seven patients as defined according Simon''s two-stage phase II design were enrolled. They received TLC D-99 at the dosage of 60 mg/m2 plus CTX 600 mg/m2, with cycles repeated every 3 weeks. Cardiac function was assessed by ultrasonography at baseline and every two cycles. RESULTS: The principal characteristics of the 67 enrolled patients were as follows: median age 60 years (range 33-75), median World Health Organization performance status of 1 (range 0-2) and dominant disease site (viscera/bone/soft tissue): 47/15/15 There were nine complete responses and 32 partial responses for an overall response rate of 64%; a further 14 patients had stable disease and the remaining nine patients progressed. Median number of administered cycles was six. Median duration of response was 10 and 9 months, respectively, for complete responders and partial responders. Median duration of survival was 17+ months (range 3 to 33+). Hematological toxicity consisted in leucopenia (G1-G2) in 21 patients and anemia (G1-G2) in 20 patients; G1 thrombocytopenia was observed only in 2 patients. Non-hematological toxicity was generally mild with G1-G2 nausea/vomiting in 23 patients and G1-G2 mucositis in 10. Hair loss was registered in 30 patients and it was G2 in 14 patients. As to concern cardiac toxicity, one patient developed an asymptomatic 20% decline of left ventricular ejection fraction from the baseline value. CONCLUSIONS: The results of our study show that the combination of TLC D-99 plus CTX is active and well tolerated, with no unexpected toxicity.