Cardiac dysfunction in the trastuzumab clinical trials experience.
OBJECTIVE
This study sought to estimate cardiac dysfunction (CD) risk for patients receiving trastuzumab; to characterize observed CD by severity, treatment, and clinical outcome; to assess effects of baseline clinical risk factors on CD; and to assess effects of cumulative doses of anthracyclines and trastuzumab on CD.


METHODS
A retrospective review of records for patients enrolled onto any of seven phase II and III trastuzumab clinical trials was performed. Predefined criteria were used for the diagnosis, and the New York Heart Association functional classification system was used to document CD severity. Product-limit estimates were used to summarize the cumulative anthracycline and trastuzumab doses at the time of CD onset.


RESULTS
Patients treated with trastuzumab were found to be at an increased risk for CD. The incidence was greatest in patients receiving concomitant trastuzumab and anthracycline plus cyclophosphamide (27%). The risk was substantially lower in patients receiving paclitaxel and trastuzumab (13%) or trastuzumab alone (3% to 7%); however, most of these patients had received prior anthracycline therapy. CD was noted in 8% of patients receiving anthracycline plus cyclophosphamide and 1% receiving paclitaxel alone. Most trastuzumab-treated patients developing CD were symptomatic (75%), and most improved with standard treatment for congestive heart failure (79%).


CONCLUSIONS
Trastuzumab is associated with an increased risk of CD, which is greatest in patients receiving concurrent anthracyclines. In most patients with metastatic breast cancer, the risk of CD can be justified given the improvement in overall survival previously reported with trastuzumab.
Seidman
Andrew
A
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. seidmana@mskcc.org
Hudis
Clifford
C
Pierri
Mary Kathryn
MK
Shak
Steven
S
Paton
Virginia
V
Ashby
Mark
M
Murphy
Maureen
M
Stewart
Stanford J
SJ
Keefe
Deborah
D
D018943:Anthracyclines / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy; D009202:Cardiomyopathies / Q000139:chemically induced*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D000068878:Trastuzumab
D018943:Anthracyclines; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D000068878:Trastuzumab; D017239:Paclitaxel