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

Research output: Contribution to journalArticle

23 Citations (Scopus)

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/m 2) 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.

Original languageEnglish (US)
Pages (from-to)111-120
Number of pages10
JournalBreast Cancer Research and Treatment
Volume121
Issue number1
DOIs
StatePublished - May 2010

Fingerprint

docetaxel
Liposomes
Doxorubicin
Breast Neoplasms
Hand-Foot Syndrome
Heart Failure
Heart Rate
Febrile Neutropenia
Disease-Free Survival
Therapeutics
liposomal doxorubicin
Trastuzumab

Keywords

  • Cardiotoxicity
  • Docetaxel
  • Metastatic breast cancer
  • Pegylated liposomal doxorubicin
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase II trial of pegylated liposomal doxorubicin plus docetaxel with and without trastuzumab in metastatic breast cancer : Eastern Cooperative Oncology Group Trial E3198. / Wolff, Antonio C.; Wang, Molin; Li, Hailun; Pins, Michael R.; Pretorius, Florence J.; Rowland, Kendrith M.; Sparano, Joseph A.; Davidson, Nancy E.

In: Breast Cancer Research and Treatment, Vol. 121, No. 1, 05.2010, p. 111-120.

Research output: Contribution to journalArticle

Wolff, Antonio C. ; Wang, Molin ; Li, Hailun ; Pins, Michael R. ; Pretorius, Florence J. ; Rowland, Kendrith M. ; Sparano, Joseph A. ; Davidson, Nancy E. / Phase II trial of pegylated liposomal doxorubicin plus docetaxel with and without trastuzumab in metastatic breast cancer : Eastern Cooperative Oncology Group Trial E3198. In: Breast Cancer Research and Treatment. 2010 ; Vol. 121, No. 1. pp. 111-120.
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AB - 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/m 2) 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.

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