Annals of Oncology 15:440-449, 2004
© 2004 European Society for Medical Oncology
Original Paper |
Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYXTM/Doxil®) versus conventional doxorubicin for first-line treatment of metastatic breast cancer
Received 26 June 2003; revised 16 October 2003; accepted 16 December 2003Background:
This study was designed to demonstrate that efficacy [progression-free survival (PFS)] of CAELYXTM [pegylated liposomal doxorubicin HCl (PLD)] is non-inferior to doxorubicin with significantly less cardiotoxicity in first-line treatment of women with metastatic breast cancer (MBC).
Patients and methods:
Women (n = 509) with MBC and normal cardiac function were randomized to receive either PLD 50 mg/m2 (every 4 weeks) or doxorubicin 60 mg/m2 (every 3 weeks). Cardiac event rates were based on reductions in left ventricular ejection fraction as a function of cumulative anthracycline dose.
Results:
PLD and doxorubicin were comparable with respect to PFS [6.9 versus 7.8 months, respectively; hazard ratio (HR) = 1.00; 95% confidence interval (CI) 0.82–1.22]. Subgroup results were consistent. Overall risk of cardiotoxicity was significantly higher with doxorubicin than PLD (HR = 3.16; 95%CI 1.58–6.31; P <0.001). Overall survival was similar (21 and 22 months for PLD and doxorubicin, respectively; HR = 0.94; 95%CI 0.74–1.19). Alopecia (overall, 66% versus 20%; pronounced, 54% versus 7%), nausea (53% versus 37%), vomiting (31% versus 19%) and neutropenia (10% versus 4%) were more often associated with doxorubicin than PLD. Palmar-plantar erythrodysesthesia (48% versus 2%), stomatitis (22% versus 15%) and mucositis (23% versus 13%) were more often associated with PLD than doxorubicin.
Conclusions:
In first-line therapy for MBC, PLD provides comparable efficacy to doxorubicin, with significantly reduced cardiotoxicity, myelosuppression, vomiting and alopecia.
,2
1 Kent Cancer Center, Maidstone, UK; 2 Ichilov Hospital, Tel Aviv, Israel; 3 Oncologia Medica I Ist., Genova, Italy; 4 Frauenklinik der Ruprecht-Karls-Universitat Vosstrasse, Heidelberg, Germany; 5 Oncologia Medica & Ematologie, Istituto Clinico Humanitas, Rozzano (MI), Italy;6 Sha’are Zedek Medical Center, Jerusalem, Israel; 7 Maastricht University Medical Center, Maastricht, The Netherlands; 8 Oncology Clinic, Poznan, Poland; 9 Newcastle Mater Misericordiae Hospital, Waratah, Australia; 10 Hospital Dipreca, Santiago, Chile; 11 Schering-Plough Research Institute, Kenilworth, NJ, USA
Key words: cardiotoxicity, pegylated liposomal doxorubicin
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