Phase II Study of UFT with Leucovorin Plus Hepatic Arterial Infusion with Irinotecan, 5-Fluorouracil and Leucovorin for Non-Resectable Liver Metastases of Colorectal Cancer

Abstract

Background: Compared with systemic therapy, hepatic arterial infusion (HAI) increases the response to fluoropyrimidines. Methods: Thirty-one patients with non-resectable, colorectal cancer (CRC) liver metastases received irinotecan 120 mg/m², followed by leucovorin (LV) 20 mg/m² and 5-fluorouracil (5-FU) 500 mg/m² administered by HAI every 2 weeks, plus UFT (tegafur-uracil) 200 mg/m²/day with LV 30 mg/day on days 1–22, followed by a 6-day rest. Results: The objective response rate was 65% (all 20 patients achieving a partial response). Ten patients (32%) had stable disease. The median time to progression (TTP) and overall survival (OS) were 12 and 36 months. OS was similar in patients with low versus high expression of thymidylate synthase (TS) and/or dihydropyrimidine dehydrogenase (DPD). The regimen was well tolerated. Conclusions: UFT with LV plus HAI irinotecan and 5-FU/LV was a feasible and effective treatment for non-resectable CRC liver metastases, increasing response, TTP and OS. TS and DPD levels in liver metastases did not predict outcome.

Systematic review and meta-analysis of hepatic arterial infusion chemotherapy as bridging therapy for colorectal liver metastases

“…The most consistent criteria for unresectable disease were i) inability to perform a complete resection [42,46,49,50,52]; ii) insufficient projected residual functional liver parenchyma [42,45,46,49,52] and iii) extra-hepatic metastases [42,44,45,50] ( Table 3). …”

Hepatic arterial infusion in colorectal carcinoma: is anatomical targeting still relevant in an era of molecularly targeted therapy?

“…In a retrospective report, the experience with sequential administration of HAI of 5-fluorouracil followed by the systemic combination of oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX) was described with response rates after HAI and FOLFOX of 85% and 35%, respectively 63 . A number of reports have also been published on HAI of irinotecan [64][65][66] . In a phase I trial maximum tolerated dose of irinotecan administered for 5 days every 3 weeks was 25 mg/m 2 (ref.…”

“…In a pilot experience in 15 patients, objective response was observed in 5 and stable disease in 7 patients 65 . In a phase II trial HAI of irinotecan, 5-fluorouracil and leucovorin was combined with oral administration of UFT (combination of tegafur and uracil in 1 : 4 molar ratio) and leucovorin in 31 patients with metastatic colorectal carcinoma 66 . Partial response was observed in 20 (65%) patients, and median survival was 36 months.…”

Protective effects of water-soluble low-molecular-weight <I>β</I>-(1,3-1,6)d-glucan purified from <I>Aureobasidium pullulans</I> GM-NH-1A1 against UFT toxicity in mice

“…[27,28] Consequently, the combination of tegafur and uracil, termed UFT, was developed as a new chemotherapeutic drug, and has been clinically used worldwide. [29,30] However, 5-FU derivatives cause severe gastrointestinal toxicity, with diarrhoea and mucositis, and haematological toxicity (leucopenia), which appear to be dose-limiting factors. The aim of this study was to determine whether a purified water-soluble LMW b-glucan enhances the antitumour activity of UFT and protects against adverse reactions in mice bearing colon 26 tumours.…”