Uracil-tegafur and tamoxifen vs cyclophosphamide, methotrexate, fluorouracil, and tamoxifen in post-operative adjuvant therapy for stage I, II, or IIIA lymph node-positive breast cancer: a comparative study.

BACKGROUND: It has been reported that treatment with uracil-tegafur (UFT) has shown significantly better survival and relapse-free survival (RFS) than surgery alone. Therefore, we compared UFT with a combination therapy of cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients who had undergone curative surgery for axillary lymph node-positive breast cancer. METHODS: A total of 377 node-positive patients with stage I, II, or IIIA disease were registered from September 1996 through July 2000 and were randomly assigned to either 6 cycles of CMF or 2 years of UFT. In both arms, tamoxifen (TAM) was concurrently administered for 2 years. The primary end point in this study was the non-inferiority of UFT to CMF. RESULTS: No statistically significant difference between the two groups was observed with regard to the 5-year RFS rate (72.2% in the UFT and 76.3% in the CMF). Adverse event profiles differed between the two groups, with a significantly lower incidence of leukopenia and anaemia in the UFT group, as well as anorexia, nausea/vomiting, stomatitis, and alopecia, which have implications for quality of life. CONCLUSION: UFT administered in combination with TAM holds promise in the treatment of lymph node-positive early breast cancer. On stratified analysis, the recurrence rate in the UFT group was found to be better in oestrogen receptor (ER)-positive patients. Tegafur-based treatment should be evaluated by a prospective randomised trial conducted in ER-positive patients.

Estimation of absorption enhancement by medium-chain fatty acids in rat large intestine.

The absorption enhancement by the sodium salts of several fatty acids was investigated in rat large intestine for model compounds having a wide range of molecular weight. Sodium caprylate (C8), sodium caprate (C10), sodium laurate (C12), which are categorized in medium-chain fatty acid, and sodium oleate (C18:1), long-chain unsaturated fatty acid, were employed as lipoidal adjuvants. Phenol red (MW=354.4), glycyrrhizin (822.9), fluorescein isothiocyanate-dextran-4 (FD-4, 4400), FD-10 (9400) and FD-40 (38900) were selected as model compounds for the assessment of the enhancing effect of the lipoidal adjuvants. The absorption of phenol red was promoted at the highest level, about 20 times higher by C12 and C18:1 than the control. The absorption rate - time profiles calculated by deconvolution method showed that C12 takes effect most rapidly and efficiently. In the case of glycyrrhizin, four adjuvants including C12 showed almost the same improvement of the absorption, about 30-40 times larger than the control. C8 and sodium citrate did not significantly enhance the absorption of those model compounds. For FD-4, FD-10 and FD-40, C10, C12 and C18:1 revealed almost the same enhancing effect and the absorption of FD-4, FD-10 and FD-40 was enhanced about 80 times, 1000-1800 times and about 200 times, respectively, larger than the control. The enhancement ratio, the ratio of AUC with adjuvant to AUC of control, suggests that these lipoidal adjuvants would improve most efficiently the absorption of the compound having the molecular weight of around 10000. Furthermore, C12 was suggested to be an effective adjuvant for the compounds with the wide range of molecular weight.