Multicentre phase II study of leucovorin plus pharmacokinetic modulating chemotherapy for metastatic colorectal cancer.

The optimal administration of 5-fluorouracil (5-FU)/leucovorin (LV) for colorectal cancer (CRC) has yet to be fully defined although evidence of the combination has already been established. In a multicentre phase II study, pharmacokinetic modulating chemotherapy (PMC), which is based on the concept that continuous intravenous 5-FU infusion can be enhanced by low-dose oral uracil/tegafur, was combined with LV and administered. Thirty-seven patients were enrolled. The objective response rate was 31.4% and the tumour stabilization rate was 85.7%. The most common toxic effects were neutropenia and hand-foot skin reactions although no life-threatening grade 3-4 toxicities were noted. Grade 3 toxicities such as neutropenia, nausea, diarrhoea and oesophagitis occurred in one patient each. We identified the usefulness of a new type of infusional 5-FU combined with LV for the treatment of CRC. The combination of PMC and LV is active with an acceptable rate of toxicity as a first-line treatment of advanced CRC.