Topoisomerase-1, thymidylate synthase primary tumour expression and clinical efficacy of 5-FU/CPT-11 chemotherapy in advanced colorectal cancer patients

While several studies have reported that thymidylate synthase (TS) tumour expression can be a reliable predictive marker of clinical response to 5-Fluorouracil (5-FU) for advanced colorectal cancer patients, only a few studies that searched for predictive factors of irinotecan (CPT-11) clinical response are available. The aim of the present study has been to verify the predictive value of immunohistochemical topoisomerase-I (Topo-I) and TS primary tumour expression in a consecutive series of 62 advanced colorectal cancer patients that received a first line 5-FU/CPT-11 chemotherapy. TS and Topo-I immunostaining was observed in 76% and 43% of tumours, respectively, resulting in a significant relationship within each tumour (r=0.365, p<0.004). Patients with different TS tumour expression showed a similar percentage of Objective Clinical Response, OR (40% vs. 28% of OR in low and high TS-expressing tumours, respectively, p=ns); also patients with different Topo-I tumour expression did no; show a different probability of OR (39% vs. 29% of OR in high and low Topo-I expressing tumours, respectively; p=ns). The tumour expression of these 2 biomarkers also did not impact on time to progression and overall survival of patients. Furthermore, the combined analysis of TS and Topo-I tumour status did not permit to individualize subgroups of patients with different probability of OR. With multivariate analysis, only patient Performance Status significantly impacted on OS (Hazard ratio 4.87; p=0.02) of these patients. We can conclude that high TS tumour expression seems not to preclude a clinical activity for 5-FU/CPT-11 polichemotherapy in advanced colorectal cancer patients; furthermore, clinical response and prognosis of colorectal cancer patients treated with 5-FU/CPT-11 regimen do not differ in tumours with different TS or Topo-I expression. (C) 2004 Wiley-Liss, Inc.