Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility.
|Abstract||To assess the spectrum and reversibility of the cardiotoxicity observed in the adjuvant trastuzumab trials.|
Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31.
|Journal Title||journal of clinical oncology : official journal of the american society of clinical oncology|
|Publication Year Start||2007-01-01|
PMID- 17687157 OWN - NLM STAT- MEDLINE DCOM- 20070830 LR - 20151119 IS - 1527-7755 (Electronic) IS - 0732-183X (Linking) VI - 25 IP - 23 DP - 2007 Aug 10 TI - Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility. PG - 3525-33 AB - 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. FAU - Telli, Melinda L AU - Telli ML AD - Department of Medicine, Division of Medical Oncology, Stanford University, Stanford, CA, USA. [email protected] FAU - Hunt, Sharon A AU - Hunt SA FAU - Carlson, Robert W AU - Carlson RW FAU - Guardino, Alice E AU - Guardino AE LA - eng PT - Journal Article PT - Review PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents) RN - P188ANX8CK (Trastuzumab) SB - IM CIN - J Clin Oncol. 2007 Dec 1;25(34):5532-3; author reply 5533-4. PMID: 18048835 MH - Aged MH - Antibodies, Monoclonal/*adverse effects MH - Antibodies, Monoclonal, Humanized MH - Antineoplastic Agents/*adverse effects MH - Breast Neoplasms/complications/*drug therapy MH - Clinical Trials as Topic MH - Drug-Related Side Effects and Adverse Reactions MH - Female MH - Follow-Up Studies MH - Heart/*drug effects MH - Heart Diseases/*chemically induced MH - Heart Failure/*chemically induced/drug therapy MH - Humans MH - Middle Aged MH - Trastuzumab MH - Ventricular Dysfunction, Left/*chemically induced/drug therapy RF - 26 EDAT- 2007/08/10 09:00 MHDA- 2007/08/31 09:00 CRDT- 2007/08/10 09:00 PHST- 2007/08/10 09:00 [pubmed] PHST- 2007/08/31 09:00 [medline] PHST- 2007/08/10 09:00 [entrez] AID - 25/23/3525 [pii] AID - 10.1200/JCO.2007.11.0106 [doi] PST - ppublish SO - J Clin Oncol. 2007 Aug 10;25(23):3525-33. doi: 10.1200/JCO.2007.11.0106.