Cardiac troponin I elevation and overall survival among cancer patients receiving investigational compounds during phase I trials

ObjectiveTo identify factors associated with troponin elevation and to measure the effect of elevated troponin on survival in cancer patients participating in phase I trials.MethodsClinical characteristics, cardiovascular risk factors, and biological data from consecutive patients treated in phase I trials (January 2010-November 2012) were reviewed. Troponin value was measured for each patient before study-drug administration and then weekly. Cardiac troponin I was considered elevated if > 0.06 ng/mL. Incidence and relative risk of elevated troponin adjusted for potential confounding factors were estimated using multivariable Poisson regression models. A conditional Cox proportional hazards model was used to compare overall survival in patients with elevated troponin matched to patients without troponin elevation recruited in the same trial.ResultsOf 463 patients, 42 (9%) experienced ≥ 1 episode of troponin I elevation after a median of 5 weeks (interquartile range: 3-13) from drug initiation. Crude incidence of troponin elevation was 36/1000 person-months (95% confidence interval [CI]: 25-47). Troponin elevation was more frequent in patients exposed to antiangiogenic compounds versus other treatments (relative risk: 1.9, 95% CI: 1.1-3.3). Median overall survival from drug initiation was 9 months (95% CI: 8-10), and 8 months (95% CI: 2-13) in patients with troponin elevation. In the case-control analysis, risk of death was higher in patients with troponin elevation (hazard ratio: 2.9, 95% CI: 1.2-6.8).ConclusionPatients exposed to antiangiogenic compounds had a higher risk of troponin elevation, which was associated with a higher risk of death.