cardiovascular adverse events after cancer treatment
Conditions
Interventions
None listed
Sponsors
Universitair Medisch Centrum Groningen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. any proven cancer treated with curative intent; 2. age >= 18 and = 3 months after end of cancer treatment which included the maximum tolerable dose of anthracyclines (i.e. 450 to 500 mg/m2 doxorubicin or 850 to 900 mg/m2 epirucibin); [T-TOX]: severe cardiovascular toxicity* within 1 to 6 cycles of trastuzumab (6 mg/kg/3wks or equivalent); [T-NO]: >= 3 months after end of cancer treatment which included a year of trastuzumab (18 cycles of 6 mg/kg/3wks or equivalent). [C-TOX]: severe cardiovascular toxicity* during 1 to 3 cycles of cisplatin (i.e. 100 to 300 mg/m2); [C-NO]: >= 1 year after end of cancer treatment which included high-dose cisplatin (i.e. a cumulative dose of 400 to 1000 mg/m2); [B-TOX]: severe cardiovascular toxicity* during 1 to 3 cycles of bleomycin (i.e. 90 to 270 USP); [B-NO]: >= 1 year after end of cancer treatment which included high-dose bleomycin (i.e. a cumulative dose >= 360 USP);;* Severe cardiovascular toxicity is defined as any of grade 3 - 4 toxicity according to CTCAE 4.03, including but not limited to: * - in the category *Cardiac disorders*: o acute coronary syndrome (symptomatic, unstable angina and/or acute myocardial infarction, cardiac enzymes abnormal, hemodynamically stable - or more severe); o cardiac arrest; o heart failure (severe with symptoms at rest or with minimal activity or exertion; intervention indicated - or more severe) o left ventricular systolic dysfunction (symptomatic due to drop in ejection fraction responsive to intervention - or more severe); o myocardial infarction (severe symptoms; cardiac enzymes abnormal; hemodynamically stable; ECG changes consistent with infarction - or more severe); o restrictive cardiomyopathy (symptomatic heart failure or other cardiac symptoms, responsive to intervention - or more severe); o right ventricular dysfunction (severe symptoms, associated with hypoxemia, right heart failure; oxygen indicated - or more severe); * - in the category *Nervous system disorders*: o stroke (severe neurologic deficit - or more severe); * - in the category *Vascular disorders*: o peripheral ischemia (recurring or prolonged (>= 24 hours) and/or invasive intervention indicated - or more severe); o thromboembolic event (thrombosis (e.g., uncomplicated pulmonary embolism [venous], non-embolic cardiac mural [arterial] thrombus), medical intervention indicated - or more severe); * - in the category *Respiratory, thoracic and mediastinal disorders*: o pneumonitis (severe symptoms; limiting self-care ADL; oxygen indicated - or more severe); o pulmonary fibrosis (severe hypoxemia; evidence of right-sided heart failure; radiographic pulmonary fibrosis > 50 - 75% - or more severe); * - in the category *Renal and urinary disorders*: o acute kidney injury (creatinine > 3 x baseline or > 4.0 mg/dL; hospitalization indicated - or more severe); o chronic kidney disease (estimated Glomerular Filtration Rate or creatinine clearance 29 - 15 ml/min/1.73 m2 - or more severe).
Exclusion criteria
Exclusion criteria: 1. history of cardiovascular disease prior to start of cancer treatment, as evidenced by any of the following: a. symptomatic or treated cardiovascular disease prior to start of cancer treatment; b. LVEF 3; 5. pregnant or lactating female. Furthermore, there are specific exclusion criteria for the *resilient* subject groups [A-NO], [T-NO], [C-NO], and [B-NO]: 6. history of cardiovascular disease during or after cancer treatment, as evidenced by any of the following: a. any symptomatic or treated cardiovascular disease; b. LVEF
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint will be a comparison in iPSC-CM/iPSC-EC morphology, function and molecular profile (RNA sequencing, proteomic profiling) before and after exposure to anthracyclines, trastuzumab, cisplatin, bleomycin and radiation in iPSC derived from the highly susceptible groups and the highly resilient control groups. | — |
Secondary
| Measure | Time frame |
|---|---|
| n.a. | — |
Countries
Netherlands
Outcome results
None listed