Randomized study of doxorubicin-based chemotherapy regimens, with and without sildenafil, with analysis of intermediate cardiac markers
Abstract
BackgroundDoxorubicin chemotherapy is used across a range of adult and pediatric malignancies. Cardiac toxicity is common, and dysfunction develops over time in many patients. Biomarkers used for predicting late cardiac dysfunction following doxorubicin exposure have shown promise. Preclinical studies have demonstrated potential cardioprotective effects of sildenafil.MethodsWe sought to confirm the safety of adding sildenafil to doxorubicin-based chemotherapy and assess N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) and high sensitivity cardiac troponin I (hsTnI) as early markers of anthracycline-induced cardiotoxicity. We randomized 27 patients (ages 31–77, 92.3% female) receiving doxorubicin chemotherapy using a blocked randomization scheme with randomly permuted block sizes to receive standard chemotherapy alone or with the addition of sildenafil. The study was not blinded. Sildenafil was dosed at 100 mg by mouth daily during therapy; patients took sildenafil three times daily on the day of doxorubicin. Doxorubicin dosing and schedule were dependent on the treatment regimen. Echocardiography was obtained prior to initiation of treatment and routinely thereafter up to 4 years. NT-proBNP and hsTnI were obtained with each cycle before, 1-3 h after, and 24 h after doxorubicin.ResultsFourteen patients were randomized to receive standard doxorubicin chemotherapy alone (14 treated and analyzed), while 13 patients were randomized to the experimental doxorubicin and…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 27 participants or records.
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