Using preoperative UFT to predict sensitivity to fluoropyrimidines in colorectal cancer

This study was designed to determine if histopathologic evaluation of patients with resectable colorectal cancer following preoperative chemotherapy with uracil and tegafur with a molar ratio of 4:1 (UFT) could predict chemosensitivity to postoperative fluoropyrimidines to prevent recurrence of disease. In this prospective randomized study involving 152 colorectal cancer patients, UFT 600 mg/day was administered for 10 days prior to surgery. Histopathology of the resected tumor was assessed, including the amount of necrosis or disappearance of tumor, and patients were thereafter stratified into two groups according to tumor response to preoperative therapy--grade > or = 2 (sensitive) vs those with grade < or = 1B (not sensitive). The patients were then randomly assigned to postoperative adjuvant UFT (400 mg/day for 12 months) or no treatment. At the time of this evaluation, the mean total preoperative UFT dose per patient was 7.76 g +/- 3.27 g. Thirteen patients were considered ineligible; therefore, 139 patients were included in the analysis. Stratification resulted in 22 (15.8%) cases in the sensitive group, of which 13 received adjuvant chemotherapy and nine were assigned to no treatment; 117 (84.2%) patients were considered nonsensitive, 60 of whom received adjuvant chemotherapy, and 57 of whom received no adjuvant therapy. Among nonsensitive patients, 3-year survival rates were 87.6% with adjuvant chemotherapy and 84.9% with no therapy, indicating no significant difference between groups. Among responders, however, there was a significant difference in 3-year survival rates: 100% for the adjuvant group and 62.5% for the no-treatment group (P = .0351). These findings suggest that histopathologic assessment following preoperative UFT chemotherapy provides information to predict fluoropyrimidine sensitivity. We believe grade 1B patients (19.8%) may respond to modulated fluorouracil. We also recommend the use of other drugs, such as irinotecan (CPT-11 [Camptosar]) and oxaliplatin, for patients with tumor responses of grades 0 and 1A.