A randomized controlled trial of postoperative adjuvant immunochemotherapy for colorectal cancer with oral medicines.

ABSTRACT

Postoperative adjuvant chemotherapy reportedly improves advanced colorectal cancer patients' survival, however, it is necessary to assess what regimens are useful. Doxifluridine (5'-DFUR) is an intermediate of capecitabine approved in Europe and USA to treat metastatic colorectal cancer. 5'-DFUR is metabolized to 5-fluorouracil (5-FU) by thymidine phosphorylase existing in tumor at high concentrations, suggesting high 5-FU levels in tumor tissues and lesser complications. Present study compared usefulness of 5'-DFUR to that of oral 5-FU. Patients were enrolled at 38 centers from April 1993 to September 1996. They had diagnosed colorectal cancer of TNM stages II and III, and underwent macroscopic curative resection. Patients were prestratified into colon or rectum cancer and allocated into either 5'-DFUR (5'-DFUR 460 mg/m(2)/day + PSK 3 g/day) or 5-FU (5-FU 115 mg/m(2)/day + PSK 3 g/day) group by dynamic randomization (stratification factors such as depth of tumor, degree of lymph node metastasis, and location of tumor). Drugs were orally administered daily from postoperative week 2 to 54, with 6 mg/m(2) mitomycin C at operation and following days. Subjects for analysis were 277 in 5'-DFUR and 281 in 5-FU groups. Median follow-up was 6.5 years. Although no differences in overall survival curves were detected, multivariate analysis showed that 5'-DFUR + PSK regimen was a significantly better prognostic factor in patients with Dukes B or C (risk ratio, 1.451; p=0.048); with tumor depth of pT3 or pT4 (risk ratio, 1.568; p=0.020). For patients with advanced colorectal cancer, 5'-DFUR + PSK therapy may possibly be more useful than 5-FU + PSK, but further study is required.