Prognostic significance of thymidylate synthase in patients with metastatic colorectal cancer who receive protracted venous infusions of 5-fluorouracil

被引:14
作者
Hosokawa A. [1 ]
Yamada Y. [1 ]
Shimada Y. [1 ]
Muro K. [1 ]
Hamaguchi T. [1 ]
Morita H. [1 ]
Araake M. [1 ]
Orita H. [1 ]
Shirao K. [1 ]
机构
[1] Gastrointestinal Oncology Division, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045
关键词
Colorectal cancer; Continuous infusion; Fluorouracil; Prognostic factor; Thymidylate synthase;
D O I
10.1007/s10147-004-0425-1
中图分类号
学科分类号
摘要
Background. This study was conducted to evaluate the prognostic significance of thymidylate synthase (TS) expression in the tumor tissue of patients with metastatic colorectal cancer (CRC) who received protracted venous infusions of 5-fluorouracil (5-FU). Methods. We retrospectively analyzed the prognostic value of TS expression as compared with other clinical prognostic factors in 57 patients with metastatic CRC. Results. On univariate analysis, survival was significantly related to TS expression (low vs high; P = 0.0015), alkaline phosphatase (ALP) level (<300 vs ≥300 IU/l; P = 0.0037), performance status (0 or 1 vs 2 or 3; P = 0.0073), and white blood cell count (<10 000/mm3 vs ≥10 000/mm3; P = 0.0001), with number of metastatic sites (1 vs ≥2; P = 0.06) approaching significance. On multivariate analysis, survival was significantly related to TS expression (hazard ratio [HR], 2.97) and ALP level (HR, 2.26). Conclusion. In patients with metastatic CRC who received protracted venous infusions of 5-FU, TS expression was related to survival independently of other established clinical prognostic factors.
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页码:388 / 392
页数:4
相关论文
共 18 条
[1]  
Lokich J., Bothe A., Fine N., Et al., Phase I study of protracted venous infusion of 5-fluorouracil, Cancer, 48, pp. 2565-2568, (1981)
[2]  
Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer, J Clin Oncol, 16, pp. 301-308, (1998)
[3]  
Graf W., Bergstrom R., Pahlman L., Et al., Appraisal of a model for prediction of prognosis in advanced colorectal cancer, Eur J Cancer, 30 A, pp. 453-457, (1994)
[4]  
Kemeny N., Brawn Jr. D.W., Prognostic factors in advanced colorectal carcinoma. Importance of lactic dehydrogenase level, performance status, and white blood cell count, Am J Med, 74, pp. 786-794, (1983)
[5]  
Massacesi C., Norman A., Price T., Et al., A clinical nomogram for predicting long-term survival in advanced colorectal cancer, Eur J Cancer, 36, pp. 2044-2052, (2000)
[6]  
Kohne C.H., Cunningham D., Costanzo F.D., Et al., Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: Results of a multivariate analysis of 3825 patients, Ann Oncol, 13, pp. 308-317, (2002)
[7]  
Aschele C., Debernardis D., Casazza S., Et al., Immunohistochemical quantitation of thymidylate synthase expression in colorectal cancer metastases predicts for clinical outcome to fluorouracil-based chemotherapy, J Clin Oncol, 17, pp. 1760-1770, (1999)
[8]  
Leichman C.G., Lenz H.J., Leichman L., Et al., Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluorouracil and weekly leucovorin, J Clin Oncol, 10, pp. 3223-3229, (1997)
[9]  
Okabe H., Tsujimoto H., Fukushima M., Preparation of the antibodies against recombinant human thymidylate synthase for the detection of its intratumoral levels and the application to sensitivity-study of 5-fluorouracil, Oncol Rep, 4, pp. 685-690, (1997)
[10]  
Johnston P.G., Fisher E.R., Rockette H.E., Et al., The role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancer, J Clin Oncol, 12, pp. 2640-2647, (1994)