476P - Trastuzumab-induced early cardiac dysfunction assessed by speckle tracking echocardiography: correlation with chronic inflammation and oxidative str...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anti-Cancer Agents & Biologic Therapy
Complications of Treatment
Presenter Mariele Dessi'
Authors M. Dessi'1, G. Mantovani2, C. Madeddu1, L. Orgiano1, P. Alessandra3, C. Cadeddu3, G. Antoni3, R. Serpe1, G. Mercuro3
  • 1Department Of Medical Oncology, University of Cagliari, 09042 - Cagliari/IT
  • 2University of Cagliari, 09042 - Cagliari/IT
  • 3Department Of Cardiovascular Diseases, University of Cagliari, 09042 - Cagliari/IT

Abstract

Background

Trastuzumab (TZM) was shown to be very effective in patients with breast cancer overexpressing HER-2 in the neoadjuvant, adjuvant and metastatic setting. It has a mild cardiac toxicity which may increase when administered in combination with anthracyclines. The “Speckle Tracking Echocardiography” (STE), able to assess cardiac mechanics [cardiac torsion movements and the global, circumferential, radial and longitudinal Strain (S) and Strain Rate (SR)], and identify at an early stage left ventricular dysfunction, was used for cardiac monitoring. The present study aimed to assess the STE changes induced by TZM and correlate them with changes of chronic inflammation and oxidative stress markers.

Methods

A phase IV, prospective, non-randomized study was designed: planned sample size 60 patients. Inclusion criteria: 18–70 yo women with HER-2 + ve breast cancer receiving TZM, LVEF ≥55%; ECOG PS score 0-2, no history of cardiac disease. The STE parameters (global, circumferential, radial and longitudinal S and SR) and chronic inflammation (IL-6 and TNF-α)/oxidative stress (reactive oxygen species and gluthatione peroxidase) markers were assessed at baseline, after each three-weekly TZM administration, up to the 8th TZM dose.

Results

At September 2011, 30 patients (mean ± SD age 53 ± 10 y) were enrolled and completed the study. A significant reduction of the peak of radial and circumferential SR (p < 0.01 and p < 0.005) as first sign of systolic dysfunction was observed at the 3rd TZM dose. A significant reduction of the peak of longitudinal SR (p < 0.01) was observed at the 4th TZM dose. As for laboratory parameters, TNF-α increased significantly at the 2nd and 3rd TZM dose, whilst the remaining laboratory parameters did not change significantly.

Conclusions

These preliminary results suggest that TZM treatment induces an early preclinical cardiac systolic dysfunction which correlates with an increase of TNF-α. The study is in progress to reach the planned sample size, monitor patients for an adequate follow-up time and eventually select patients candidates for an effective cardioprotective treatment.

This study was Funded by AIRC - project number 8679.

Disclosure

All authors have declared no conflicts of interest.