Breast Cancer Research and Treatment

, Volume 121, Issue 1, pp 111–120 | Cite as

Phase II trial of pegylated liposomal doxorubicin plus docetaxel with and without trastuzumab in metastatic breast cancer: Eastern Cooperative Oncology Group Trial E3198

  • Antonio C. Wolff
  • Molin Wang
  • Hailun Li
  • Michael R. Pins
  • Florence J. Pretorius
  • Kendrith M. Rowland
  • Joseph A. Sparano
  • Nancy E. Davidson
Clinical trial


The purpose of this trial was to determine cardiac toxicity and overall efficacy of the pegylated liposome doxorubicin (PLD)–docetaxel couplet alone if HER2-negative metastatic breast cancer (internal control) or with trastuzumab if HER2-positive disease. Upon central HER2 confirmation, 84 eligible patients received induction with PLD (30 mg/m2) and docetaxel (60 mg/m2) every 3 weeks (maximum eight cycles), alone if HER2-negative (arm A; N = 38) or plus trastuzumab (4 mg/kg once, then 2 mg/kg weekly) if HER2-positive disease (arm B; N = 46) as first-line therapy. Maintenance therapy (without PLD) allowed. Primary objectives were to determine whether congestive heart failure (CHF) rate >3% and the efficacy/toxicity of each arm. CHF rate was <3% in each arm. Response rate, median progression-free-, and overall survival in arms A and B were 47.4 and 45.7%, 11 and 10.6 months, and 24.6 and 31.8 months, respectively. Trastuzumab arm was associated with higher rates of hand foot syndrome (grade 3: 22 vs. 38%; P = 0.16; overall 51 vs. 75%, P = 0.03) and treatment discontinuation due to toxicity/patient withdrawal (13 vs. 28%; P = 0.11). Febrile neutropenia occurred in ~10% of patients. In conclusion, concurrent administration of trastuzumab with PLD–docetaxel was not associated with higher risk of cardiac toxicity compared with PLD–docetaxel alone, but led to excessive hand-foot syndrome.


Pegylated liposomal doxorubicin Trastuzumab Docetaxel Metastatic breast cancer Cardiotoxicity 



We acknowledge the support from Ortho Biotech Products, L.P., for the provision of investigational drug and financial support for central HER2 testing and from Genentech, Inc., for the provision of investigational drugs. We are also grateful to Dako A/S and Abbott Molecular for their support with free assay kits for central HER2 testing, and to Adekunle Raji, Susan Edgerton, and other members of the ECOG Pathology Coordinating Office. This work was supported in part by grants from the Department of Health and Human Services and the National Institutes of Health CA23318 to the ECOG statistical center, CA66636 to the ECOG data management center, CA21115 to the ECOG coordinating center and chairman’s office, CA16116 to The Johns Hopkins Kimmel Cancer Center, CA59307 to the University of Pretoria, CA13650 to the Mayo Clinic (Carle Clinic), and CA14958 to the Albert Einstein College of Medicine.


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Antonio C. Wolff
    • 1
  • Molin Wang
    • 2
  • Hailun Li
    • 2
  • Michael R. Pins
    • 3
    • 7
  • Florence J. Pretorius
    • 4
  • Kendrith M. Rowland
    • 5
  • Joseph A. Sparano
    • 6
  • Nancy E. Davidson
    • 1
    • 8
  1. 1.The Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimoreUSA
  2. 2.Dana Farber Cancer InstituteBostonUSA
  3. 3.Northwestern UniversityChicagoUSA
  4. 4.University of PretoriaPretoriaSouth Africa
  5. 5.Carle ClinicUrbanaUSA
  6. 6.Montefiore-Einstein Cancer CenterAlbert Einstein College of MedicineBronxUSA
  7. 7.Advocate Lutheran General HospitalChicagoUSA
  8. 8.University of Pittsburgh Cancer InstitutePittsburghUSA

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