Evaluation of QTc interval prolongation in patients with advanced clear cell renal cell carcinoma treated with first line sunitinib

评估接受一线舒尼替尼治疗的晚期透明细胞肾细胞癌患者的 QTc 间期延长情况

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Abstract

BACKGROUND: Sunitinib, a multitargeted tyrosine kinase inhibitor, is used in advanced clear cell renal cell carcinoma (ccRCC). Corrected QT interval (QTc) prolongation is a recognized cardiovascular toxicity of this therapy. AIM: To evaluate the incidence, timing, and severity of QTc prolongation in real-world advanced ccRCC patients treated with first-line sunitinib, compare Bazett’s and Fridericia’s correction formulas, and identify risk factors. MATERIALS AND METHODS: This retrospective single-center cohort study included 67 patients between January 2019 and June 2022. QTc was calculated manually using Bazett’s and Fridericia’s formulas and graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The incidence, timing, and severity of QTc prolongation were assessed based on the highest recorded QTc value. Statistical analyses compared QTc values between formulas and evaluated potential clinical predictors of QTc prolongation. RESULTS: The median treatment duration was 1.4 years (IQR 0.72–2.99). QTc prolongation ≥ 450ms occurred in 44.8% of patients (Bazett) and 34.3% (Fridericia) and ≥ 500ms in 7 and 6 patients, respectively. The median onset of QTc ≥ 450ms was cycle 7.9 (Bazett) and 10.4 (Fridericia). Bazett’s values were significantly higher across most treatment cycles (p < 0.05). Older age, thyroid dysfunction, smoking history, hypertension and soft-tissue metastases were associated with increased risk of QTc prolongation. CONCLUSIONS: QTc prolongation was frequent and occurred both early and later during therapy. Fridericia’s formula provided more accurate and stable values and should be preferred for monitoring. Repeated ECG measurements and close cardio-oncology collaboration are essential. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00280-026-04884-y.

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