Adjuvant chemotherapy with tegafur/uracil administration after transcatheter arterial chemoembolization for advanced hepatocellular carcinoma

Abstract

Abstract. Although transcatheter arterial chemoembolization (TACE) is considered to be an effective treatment for advanced hepatocellular carcinoma (HCC), it is difficult to achieve complete necrosis by TACE alone due to incomplete embolization and tumor angiogenesis. Recent studies have shown that tegafur/uracil (UFT ® ) inhibits tumor angiogenesis in several cancer types. Therefore, this study was conducted to test the efficacy and toxicity of the UFT administration after TACE in advanced HCC. Thirty patients with HCC who had been treated with TACE alone more than three times and had a recurrence within 6 months were enrolled. All of the patients were treated with TACE and 28 patients were randomly assigned to the UFT (UFT 300 mg/day, three days after TACE, n=14) and control groups (n=14). The primary end point was the time to treatment failure (TTF) and the secondary end points were mainly the response rate and toxicity. Administration and observation were continued up to 6 months after TACE unless local recurrence was detected or serious adverse events developed. The median TTF in the control group was 87 days, whereas in the UFT group it was 127 days, thus significantly prolonged as compared to the control group (P=0.0016). Moreover, the overall response rate (35.7%) in the UFT group was significantly higher than that in the control group (0%). As for toxicity, only 4 patients in the UFT group developed grade 1-2 toxicities such as ascites. Serious complications by TACE were not observed in either group. Notably, there were no increases in the serum VEGF levels in the UFT group whereas those in the control group increased significantly. In conclusion, UFT administration after TACE was an effective treatment and showed no severe adverse events. This regimen may have an adjuvant role and antiangiogenic function in advanced HCC.

Sorafenib Inhibits Hypoxia-Inducible Factor-1α Synthesis: Implications for Antiangiogenic Activity in Hepatocellular Carcinoma

“…Chemoembolization acts mainly via reducing the local blood flow and currently studies are aiming to decrease the consequences of secretion of proangiogenic factors after this transarterial chemoembolization (1). On the other hand, proangiogenic factors are well known to be stimulated by hypoxia that is caused by the rapid growth of tumor cells and the presence of aberrant blood vessels (2).…”

Increase of angiogenic growth factors after hepatic artery embolization in patients with neuroendocrine tumours

“…This finding implicates that an adjuvant treatment to inhibit angiogenesis may be required to make the procedure more effective. A literature search revealed that changes of the anti-angiogenic function after hepatic embolization was only examined by tegafur/uracil (UFT) administration after transcatheter arterial chemoembolization (TACE) in advanced hepatocellular carcinoma (HCC) [32]. Ueda et al found a prolonged time to treatment failure in the group who were treated with UFT compared to the control group.…”

S-1 for treatment of advanced hepatocellular carcinoma: a systematic review of the literature

“…tegafur/gimeracil/oteracil potassium, known as Tiji’ao capsule in China) was a novel oral 5-fluoro-2,4 (1 h, 3 h) pyrimidinedione (5-FU) analogue, which contained tegafur and two biochemical modulators for 5-FU. Tegafur was a metabolically activated prodrug of 5-FU, and was effective as adjuvant chemotherapy after TACE [22]. 5-Chloro-2,4-dihydroxypyridine can enhance the pharmacological actions of 5-FU by inhibiting its degradation by dihydropyrimidine dehydrogenase (DPD).…”