Lonsurf® as a cardio-gentle alternative to classical fluoropyrimidines
Summary. Classical fluoropyrimidines — 5-fluorouracil (5-FU) and capecitabine — are widely used in oncology; however, their clinical use is limited by toxicity, particularly the development of hand–foot syndrome and cardiotoxic complications. Rechallenge of these agents after an episode of cardiotoxicity is associated with a high risk of its recurrence, which complicates further therapy. In this context, special interest has been focused on trifluridine / tipiracil (TAS-102, Lonsurf®) — an oral combination drug approved for the treatment of chemorefractory metastatic colorectal cancer. Its mechanism of action is based on the incorporation of trifluridine into the DNA of tumor cells and inhibition of thymidylate synthase. Importantly, the metabolism of TAS-102 does not depend on the activity of dihydropyrimidine dehydrogenase (DPD), which distinguishes it from 5-FU and capecitabine and expands treatment options for patients with DPD deficiency. In addition, the use of Lonsurf® is not associated with a pronounced hand–foot syndrome, which improves treatment tolerability and helps maintain patients’ quality of life. Cardiotoxicity with Lonsurf® appears to be minimal; analyses of multiple clinical trials have not demonstrated a significant increase in cardiovascular events compared with placebo. This allows the drug to be considered a cardio-gentle fluoropyrimidine. Therefore, Lonsurf® represents a clinically justified alternative to classical fluoropyrimidines, with improved tolerability, a lower risk of cardiotoxicity, and independence from DPD status.
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