RESUMO
OBJECTIVE: We conducted a prospective multicentre, collaborative randomised study on postoperative adjuvant therapy in patients with stage II primary breast cancer to evaluate the effect of a combination of tegafur and uracil (UFT) on tamoxifen (TAM) plus mitomycin (MM) in patients with estrogen-receptor-positive [ER(+)] breast cancer and TAM on UFT + MM in patients with estrogen-receptor-negative [ER(-)] breast cancer. METHODS: MM (13 mg/m(2)) was intravenously administered on the day of surgery for all patients, after which patients with ER(+) were randomised to TAM 20 mg/day (treatment A) or TAM 20 mg/day and UFT 400 mg/day (treatment B). Patients who were ER(-) were randomly allocated UFT 400 mg/day (treatment C) or TAM 20 mg/day and UFT 400 mg/day (treatment D). TAM and UFT were administered orally for 2 years, starting on day 14 after surgery. ENDPOINTS: 5-year disease-free survival (5y DFS), 5-year overall survival (5y OS), and safety. RESULTS: The study commenced in November 1988 and the data cut-off was May 1997 after follow-up of the last patient for 5 years. A total of 765 patients with stage II breast cancer were enrolled. 436 patients with ER(+) [group A: 213, group B: 223] and 317 patients with ER(-) [group C: 162, group D: 155] breast cancer were eligible for this study. The rate of 5y DFS was 83.1% for group A and 90.7% for group B (p = 0.020). There was a significant difference in 5y DFS between the two groups among postmenopausal and positive lymph node metastases patients. The incidence of adverse reactions was 4% for group A and 18% for group B (p < 0.05). The rate of 5y DFS was 77.1% for group C and 85.5% for group D (p = 0.063). The rate of 5y OS was 84.7% for group C and 89.8% for group D (p = 0.216). The incidence of adverse reactions was 18% in group C and 11% in group D (p = 0.06). CONCLUSION: UFT in combination with TAM + MM showed higher efficacy than TAM + MM as a postoperative combination therapy for breast cancer in patients with ER(+) breast cancer. A trend was observed in favour of the addition of TAM to UFT + MM in postmenopausal and lymph node metastases-negative patients with ER(-) breast cancer.
RESUMO
Hepatocyte transplantation is a potential therapeutic modality for overcoming the shortage of liver donors, and the clinical application of allogeneic hepatocyte transplantation has been considered. However, there are two major problems with allogeneic hepatocyte transplantation: protection of transplanted hepatocytes from rejection and stimulation of the rapid proliferation of surviving cells. Without immunosuppression, allogeneic hepatocytes are rapidly rejected within a few days after transplantation, even though it is relatively easy to induce immunotolerance after allogeneic whole liver transplantation. Accordingly, different rejection mechanisms seem to operate after allogeneic hepatocyte transplantation and whole liver transplantation. To overcome the rejection of transplanted hepatocytes, induction of donor-specific unresponsiveness to graft without compromising the host immune system would be ideal. We previously reported that the Fas-Fas ligand system plays a critical role in the CD28-independent pathway of hepatocyte rejection. Therefore, blockade of rejection using CTLA4 immunoglobulin (CTLA4Ig) or anti-CD80/86 monoclonal antibodies and anti-FasL monoclonal antibody may prolong the survival of transplanted allogeneic hepatocytes. Furthermore, administration of hepatocyte growth factor (HGF) can promote the proliferation of allogeneic hepatocytes and this may lead to the development of a functioning liver substitute.
