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

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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