Clinical trial

Breast Cancer Research and Treatment

, Volume 121, Issue 1, pp 111-120

First online:

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. WolffAffiliated withThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Email author 
  • , Molin WangAffiliated withDana Farber Cancer Institute
  • , Hailun LiAffiliated withDana Farber Cancer Institute
  • , Michael R. PinsAffiliated withNorthwestern UniversityAdvocate Lutheran General Hospital
  • , Florence J. PretoriusAffiliated withUniversity of Pretoria
  • , Kendrith M. RowlandAffiliated withCarle Clinic
  • , Joseph A. SparanoAffiliated withMontefiore-Einstein Cancer Center, Albert Einstein College of Medicine
  • , Nancy E. DavidsonAffiliated withThe Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity of Pittsburgh Cancer Institute

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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