Effects of preoperative chemotherapy on gastric carcinoma: the relationship between histopathologic response and...

To evaluate the efficacy of preoperative chemotherapy in the treatment of gastric carcinoma, 48 previously untreated patients with locoregional advanced gastric carcinoma were consecutively enrolled in this study and received preoperative 5-fluorouracil (5-FU) or 5'-deoxy-5- fluorouridine (5'-DFUR). Histopathologically, 17 patients showed no response, 27 responded slightly, 3 moderately, and 1 had an excellent response to the chemotherapy. Based on clinical cancer staging, the overall 5-year survival rate was 79% in patients with stages IB and II cancer, 44% in patients with stage III cancer, and 14% in those with stage IV cancer. In patients with stages IB, II, and IIIA disease, the 5-year survival rate for those with a positive histopathologic response to the chemotherapy was 74%, whereas that for the nonresponders was 45%. No relationship was seen between the grade of the histopathologic response and the 5-year survival rate of patients with stage IIIB and IV carcinoma. In a second group of 27 patients who received preoperative chemotherapy with 5-FU, the effect of 5-FU was evaluated using thymidylate synthetase (TS) inhibition. Free TS and total TS were measured in the tumor samples, and the thymidylate synthetase inhibition rate (TSIR) was calculated. TSIR ranged from 0% to 90.7%. The mean TSIR was 66.2% in patients with a positive histopathologic response to chemotherapy and 30.3% in those with a negative response. Mild chemotherapy as orally administered 5-FU or 5'-DFUR was found to be useful in patients with resectable gastric cancer. Furthermore, a correlation was found in chemosensitivity, histopathologic response, and TSIR.