A Phase II Randomized Crossover Study of Liposomal Doxorubicin versus Weekly Docetaxel in the First-line Treatment of Women with Metastatic Breast Cancer

Denise A. Yardley; Howard A. Burris, III; David R. Spigel; Bobby L. Clark; Elizabeth Vazquez; Dianna Shipley; John Barton; Dana Thompson; Ignacio Montes; F. Anthony Greco; John D. Hainsworth


Clin Breast Cancer. 2009;9(4):247-252. 

In This Article

Abstract and Introduction


Purpose: We aim to compare the efficacy and toxicity of liposomal doxorubicin and weekly docetaxel as first-line treatments for patients with metastatic breast cancer (MBC).
Patients and Methods: Patients who had received no previous chemotherapy for MBC were eligible. Previous hormonal therapy, adjuvant chemotherapy, and radiation therapy were allowed. Patients were randomized to receive liposomal doxorubicin 40 mg/m2 intravenously [I.V.] every 28 days or weekly docetaxel 36 mg/m2 I.V. days 1, 8, and 15, repeated every 28 days. Patients with objective response or stable disease after 2 cycles continued treatment until tumor progression or unacceptable toxicity. At progression, patients were allowed to cross over to the other regimen. The trial was designed to detect a true difference of 10% in response rate with an 80% power.
Results: Between March 2001 and July 2007, 102 patients were randomized. The 2 groups had similar demographics; 68% of patients had received previous adjuvant chemotherapy. Liposomal doxorubicin and weekly docetaxel produced similar objective response rates (28% vs. 31%), disease control rates (48% vs. 44%), and progression-free survival (6.5 months vs. 5.5 months). Both agents were well tolerated. Both agents produced crossover responses as second-line treatment (liposomal doxorubicin, 35%; weekly docetaxel, 14%).
Conclusion: Liposomal doxorubicin is well tolerated and has activity similar to weekly docetaxel in the first-line treatment of patients with MBC.


Although several cytotoxic agents are available for the treatment of metastatic breast cancer (MBC), curative therapy is not possible in the vast majority of patients. Because of the palliative nature of treatment, sequential therapy with single agents is a common treatment strategy. Response rates to single agents are somewhat lower than those achieved with combination regimens; however, the two approaches have usually resulted in similar survival, and toxicity is minimized with single agents.[1–3] Regardless of the fact that treatment with sequential single agents is an accepted "standard" approach, the optimal sequencing of active agents is not well defined.

The anthracyclines and taxanes are the two most active classes of drugs for patients with breast cancer. Although both are routinely used in adjuvant therapy, they usually retain some activity at the time of relapse and are also commonly used for the treatment of MBC. Liposomal doxorubicin and weekly docetaxel are two agents that have particular appeal in the sequential, single-agent treatment of MBC. Liposomal doxorubicin has equivalent activity when compared with doxorubicin but minimizes many of the side effects, including cardiac toxicity.[4,5] The administration of docetaxel on a weekly schedule minimizes myelosuppression while retaining activity similar to that achieved with a standard every-3-week administration schedule.[6–8]

In this randomized phase II crossover trial, we compared the efficacy and toxicity of weekly docetaxel versus liposomal doxorubicin in the first-line treatment of patients with MBC. The crossover design allowed assessment of the activity of each agent as second-line therapy after patients had progressed on the other agent. The results of this multicenter, community-based trial are reported here.


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