Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility.

Abstract

PURPOSE:

To assess the spectrum and reversibility of the cardiotoxicity observed in the adjuvant trastuzumab trials.

DESIGN:

The design and efficacy of the major adjuvant trastuzumab trials was assessed, including the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31, North Central Cancer Treatment Group N9831, Herceptin Adjuvant, Breast Cancer International Research Group 006, and Finland Herceptin trials. The cardiotoxicity data were evaluated with a focus on the follow-up cardiac evaluations of women who were diagnosed with cardiotoxicity. Proposed mechanisms of trastuzumab-related cardiotoxicity were considered. The natural history of congestive heart failure (CHF) was reviewed with the goal of placing the trastuzumab experience in context.

RESULTS:

Up to 4% of patients enrolled onto the adjuvant trastuzumab trials experienced severe CHF during treatment. In these trials, early stopping rules that identified an unacceptable level of cardiotoxicity were never reached. Despite this, a large number of patients on these trials experienced some form of cardiotoxicity that ultimately required discontinuation of trastuzumab. Approximately 14% of patients in the NSABP B-31 trial discontinued trastuzumab because of asymptomatic decreases in left ventricular ejection fraction (LVEF). Results of follow-up cardiac evaluations of patients diagnosed with any degree of cardiotoxicity in the NSABP B-31 trial document that a clinically significant proportion of patients have sustained decrements in their LVEF to less than 50%.

CONCLUSION:

Adjuvant trastuzumab provides substantial benefits to patients with human epidermal growth factor receptor 2-positive breast cancer, however, competing immediate and long-term cardiovascular risks are a great concern. Continued cardiac follow-up of these women is of critical importance.

• Authors: Melinda L Telli, Sharon A Hunt, Robert W Carlson, Alice E Guardino
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 25 Issue 23 Pg. 3525-33 (Aug 10 2007) ISSN: 1527-7755 [Electronic] United States
• PMID: 17687157 (Publication Type: Journal Article, Review)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Trastuzumab

Topics

• Aged
• Antibodies, Monoclonal (adverse effects)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (adverse effects)
• Breast Neoplasms (complications, drug therapy)
• Clinical Trials as Topic
• Drug-Related Side Effects and Adverse Reactions
• Female
• Follow-Up Studies
• Heart (drug effects)
• Heart Diseases (chemically induced)
• Heart Failure (chemically induced, drug therapy)
• Humans
• Middle Aged
• Trastuzumab
• Ventricular Dysfunction, Left (chemically induced, drug therapy)