Breast Cancer Research and Treatment

, Volume 121, Issue 1, pp 111–120

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

Abstract

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.

Keywords

Pegylated liposomal doxorubicin Trastuzumab Docetaxel Metastatic breast cancer Cardiotoxicity 

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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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