Originally published as JCO Early Release 10.1200/JCO.2008.20.5013 on August 17 2009

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Pegylated Liposomal Doxorubicin Plus Docetaxel Significantly Improves Time to Progression Without Additive Cardiotoxicity Compared With Docetaxel Monotherapy in Patients With Advanced Breast Cancer Previously Treated With Neoadjuvant-Adjuvant Anthracycline Therapy: Results From a Randomized Phase III Study

From the Montefiore-Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY; City Oncology Hospital #62; N.N. Blokhin Cancer Research Center; and P.A. Herzen Oncology Research Institute, Moscow; N.N. Petrov Research Institute of Oncology and City Clinical Oncology Dispensary, Saint Petersburg, Russia; Regional Oncology Dispensary and State Medical Academy, Dnepropetrovsk; City Oncology Hospital, Kiev, Ukraine; and OrthoBiotech Oncology Research and Development, Johnson & Johnson Pharmaceutical Research and Development, Raritan, NJ.

Corresponding author: Joseph A. Sparano, MD, Montefiore-Einstein Cancer Center, 1825 Eastchester Rd, Bronx, NY 10461; e-mail: jsparano{at}montefiore.org.

Purpose To determine whether the combination of pegylated liposomal doxorubicin (PLD) and docetaxel significantly prolongs time to disease progression compared with docetaxel alone without an increase in cardiac toxicity in women with advanced breast cancer who had experienced relapse at least 1 year after prior adjuvant or neoadjuvant anthracycline therapy.

Patients and Methods This international, phase III study randomly assigned 751 patients to receive either docetaxel 75 mg/m² (n = 373) or PLD 30 mg/m² followed by docetaxel 60 mg/m² every 21 days (n = 378) and continued until disease progression or prohibitive toxicity. The primary end point was time to progression (TTP). Secondary end points were overall survival (OS), objective response rate (ORR), cardiac toxicity, and safety.

Results Treatment with PLD-docetaxel significantly improved median TTP from 7.0 to 9.8 months (hazard ratio [HR] = 0.65; 95% CI, 0.55 to 0.77; P = .000001) and the ORR from 26% to 35% (P = .0085). OS was similar between the two groups (HR = 1.02; 95% CI, 0.86 to 1.22). The incidence of grade 3 or 4 adverse events were similar (78% v 72%), although a higher incidence of hand-foot syndrome (24% v 0%) and mucositis/stomatitis (12% v 1%) were observed in the PLD-docetaxel combination. Protocol-defined left ventricular ejection fraction decreases and congestive heart failure were reported in 5% and 1% in both treatment arms, respectively.

Conclusion The PLD-docetaxel combination was more effective than docetaxel alone in women with metastatic breast cancer who had experienced relapse at least 1 year after prior adjuvant anthracycline therapy without an increase in cardiac toxicity, although mucocutaneous toxicity was more common.

Supported by Johnson & Johnson Pharmaceutical Research & Development.

Presented in part at the 31st San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, TX.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00091442 [ClinicalTrials.gov] .

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