title: Cardiac troponin I elevation and overall survival among cancer patients receiving investigational compounds during phase I trials.
abstract: OBJECTIVE
  To identify factors associated with troponin elevation and to measure the effect of elevated troponin on survival in cancer patients participating in phase I trials.
  
  
  METHODS
  Clinical 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 >0.06ng/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.
  
  
  RESULTS
  Of 463 patients, 42 (9%) experienced ≥1 episode of troponin I elevation after a median of 5weeks (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 9months (95% CI: 8-10), and 8months (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).
  
  
  CONCLUSIONS
  Patients exposed to antiangiogenic compounds had a higher risk of troponin elevation, which was associated with a higher risk of death.
authors.affiliation: Drug Development Department (DITEP: Département d'Innovations Thérapeutiques et Essais Précoces), Gustave Roussy Cancer campus, 94805 Villejuif, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Hollebecque
authors.affiliation: Service de biostatistique et épidémiologie, Gustave Roussy Cancer campus, 94805, Villejuif, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Lanoy
authors.affiliation: Département de biologie, Gustave Roussy Cancer campus, 94805 Villejuif, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Troallen
authors.affiliation: Service de cardiologie, Hôpital Saint-Antoine, AP-HP, Université Pierre-et-Marie-Curie, Paris-Sorbonne, 75012 Paris, France.
authors.forename: Laurie
authors.initials: L
authors.lastname: Soulat-Dufour
authors.affiliation: Drug Development Department (DITEP: Département d'Innovations Thérapeutiques et Essais Précoces), Gustave Roussy Cancer campus, 94805 Villejuif, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.affiliation: Drug Development Department (DITEP: Département d'Innovations Thérapeutiques et Essais Précoces), Gustave Roussy Cancer campus, 94805 Villejuif, France.
authors.forename: Rastislav
authors.initials: R
authors.lastname: Bahleda
authors.affiliation: Drug Development Department (DITEP: Département d'Innovations Thérapeutiques et Essais Précoces), Gustave Roussy Cancer campus, 94805 Villejuif, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Varga
authors.affiliation: Drug Development Department (DITEP: Département d'Innovations Thérapeutiques et Essais Précoces), Gustave Roussy Cancer campus, 94805 Villejuif, France.
authors.forename: Anas
authors.initials: A
authors.lastname: Gazzah
authors.affiliation: Drug Development Department (DITEP: Département d'Innovations Thérapeutiques et Essais Précoces), Gustave Roussy Cancer campus, 94805 Villejuif, France; INSERM Unit U981, Gustave Roussy Cancer Campus, 94805 Villejuif, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Postel-Vinay
authors.affiliation: Drug Development Department (DITEP: Département d'Innovations Thérapeutiques et Essais Précoces), Gustave Roussy Cancer campus, 94805 Villejuif, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ribrag
authors.affiliation: Drug Development Department (DITEP: Département d'Innovations Thérapeutiques et Essais Précoces), Gustave Roussy Cancer campus, 94805 Villejuif, France; Département de radiothérapie, Gustave Roussy Cancer campus, 94805 Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Deutsch
authors.affiliation: Drug Development Department (DITEP: Département d'Innovations Thérapeutiques et Essais Précoces), Gustave Roussy Cancer campus, 94805 Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Angevin
authors.affiliation: Service de cardiologie, Hôpital Saint-Antoine, AP-HP, Université Pierre-et-Marie-Curie, Paris-Sorbonne, 75012 Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Boccara
authors.affiliation: Service de cardiologie, Hôpital Saint-Antoine, AP-HP, Université Pierre-et-Marie-Curie, Paris-Sorbonne, 75012 Paris, France.
authors.forename: Ariel
authors.initials: A
authors.lastname: Cohen
authors.affiliation: Drug Development Department (DITEP: Département d'Innovations Thérapeutiques et Essais Précoces), Gustave Roussy Cancer campus, 94805 Villejuif, France; INSERM Unit U981, Gustave Roussy Cancer Campus, 94805 Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.affiliation: Service de cardiologie, Hôpital Saint-Antoine, AP-HP, Université Pierre-et-Marie-Curie, Paris-Sorbonne, 75012 Paris, France. Electronic address: stephane.ederhy@aphp.fr.
authors.forename: Stephane
authors.initials: S
authors.lastname: Ederhy
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D016012:Poisson Distribution; D012307:Risk Factors; D016019:Survival Analysis; D019210:Troponin I / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D019210:Troponin I
keywords: Cardio oncology; Cardiotoxicity; Drug development; Phase I trial; Troponin