Frequency and management of troponin I elevation in patients treated with molecular targeted therapies in phase I
Stephane Ederhy1, Christophe Massard, Ghislaine Dufaitre
1Department of Cardiology, Saint-Antoine University and Medical School, Paris, France.
Background:
Cardiotoxicity of molecular targeted therapies (MTT) is poorly understood and is being investigated among patients with metastatic solid tumours. The frequency of cardiac events among patients receiving MTT has been evaluated in various ways, particularly troponin elevations.
Patients And Methods:
We prospectively evaluated cardiotoxicity among patients included in Phase 1 trials receiving molecular targeted therapies (MTT) for a metastatic solid tumour. At baseline, all patients were examined before the first cycle and monitored including a clinical examination, ECG and troponin I measurement. A trans-thoracic echocardiography was performed at baseline and before each cycle. Patients were enrolled in different trials investigating : an anti-VEGF monoclonal antibody, anti-VEGFR tyrosine kinase inhibitors, and a kinesin inhibitor.
Results:
Among the 90 patients evaluated, 10 (11%) experienced chest pain and troponin I elevation (n = 2,20%) or asymptomatic troponin I elevation (n = 8, 80%) during follow-up. All patients were re-evaluated at the time of symptoms or troponin I elevation with trans-thoracic echocardiography, cardiac magnetic resonance and coronary angiography. All except one patient, had a normal LVEF during their re-evaluation. One patient exhibited ECG changes (T wave inversion). No QTc interval prolongation was found. On cardiac magnetic resonance, no late gadolinium myocardial enhancement was observed. All coronary angiographies were normal (no occlusion, or coronary stenosis >50%). All patients received beta blockers and aspirin. All Patients were re-challenged with the study drug and no cardiotoxicity was observed during follow up.
Conclusion:
Troponin elevations are frequent among patients receiving molecular targeted therapies. Re-challenging these patients after a careful evaluation and under medical treatment seems to be possible. The mechanism underlying troponin elevations does not seem to be associated with coronary occlusion nor with toxic myocarditis.
Insights
Molecular targeted therapies (MTT) can cause frequent troponin elevations in cancer patients. However, re-challenging patients with MTT after evaluation and treatment is feasible and safe, without evidence of coronary occlusion or myocarditis.
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- Cardiotoxicity from molecular targeted therapies (MTT) in metastatic solid tumors is not well understood.
- Troponin elevation is a key indicator of cardiac events in patients receiving MTT.
Purpose of the Study:
- To prospectively evaluate cardiotoxicity in patients with metastatic solid tumors receiving MTT.
- To assess the frequency and characteristics of cardiac events, particularly troponin elevations, during MTT treatment.
Main Methods:
- Prospective evaluation of 90 patients in Phase 1 trials receiving MTT (anti-VEGF antibody, anti-VEGFR TKIs, kinesin inhibitor).
- Monitoring included clinical exams, ECG, troponin I, and echocardiography at baseline and during treatment.
- Further cardiac assessment (CMR, angiography) performed upon troponin elevation or symptoms.
Main Results:
- 11% of patients experienced chest pain with troponin I elevation or asymptomatic troponin I elevation.
- Most patients maintained normal LVEF; ECG changes and QTc prolongation were rare.
- Coronary angiography was normal, ruling out significant coronary occlusion or stenosis.
Conclusions:
- Troponin elevations are common in patients undergoing MTT.
- Re-challenging patients with MTT after thorough cardiac evaluation and medical management is possible.
- The mechanism of troponin elevation appears unrelated to coronary occlusion or toxic myocarditis.
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