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.


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.
Giotta
F
F
Oncology Institute, Bari, Italy. rancescogiotta@libero.it
Lorusso
V
V
Maiello
E
E
Filippelli
G
G
Valerio
M R
MR
Caruso
M
M
Verderame
F
F
Latorre
A
A
Colucci
G
G
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000556:secondary; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008081:Liposomes; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000556:secondary
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D008081:Liposomes; D004317:Doxorubicin; D003520:Cyclophosphamide