Significance of differential expression of thymidylate synthase in normal and primary tumor tissues from patients with colorectal cancer

The role of thymidylate synthase (TS) is essential as a key rate-limiting enzyme in DNA synthesis. It is the primary target of fluorouracil and its derivates in colorectal cancer. In this study, TS mRNA expression was examined in primary tumor and normal tissues from 76 patients with high- risk stage II/III colorectal cancer by laser capture microdissection and polymerase chain reaction. Thirty (39.47%) patients were found to have higher TS expression in primary tumors with earlier stage (P = 0.018), lower histological grades (P = 0.001) and high frequency microsatellite instability (P = 0.000). Multivariate analysis showed that microsatellite instability, histological grade and number of lymph nodes examined are independent prognostic markers

A prospective randomised phase III trial of adjuvant chemotherapy with 5-fluorouracil and leucovorin in patients with stage II colon cancer

The purpose of this trial was to investigate the efficacy of adjuvant chemotherapy with 5-fluorouracil (5-FU) and leucovorin (LV) in stage II colon cancer. Patients with stage II colon cancer were randomised to either adjuvant chemotherapy with 5-FU/LV (100 mg m−2 LV+450 mg m−2 5-FU weekly, weeks 1–6, in 8 weeks cycles × 7) or surveillance only. Five hundred patients were evaluable for analyses. After a median follow-up of 95.6 months, 55 of 252 patients (21.8%) have died in the 5-FU/LV arm and 58 of 248 patients (23.4%) in the surveillance arm. There was no statistically significant difference in overall survival (OS) between the two treatment arms (hazard ratios, HR 0.88, 95% CI 0.61–1.27, P=0.49). The relative risk for tumour relapse was higher for patients on the surveillance arm than for those on the 5-FU/LV arm; however, this difference was not statistically significant (HR 0.69, 95% CI 0.45–1.06, P=0.09). Consequently, disease-free survival (DFS) was not significantly different between the two trial arms. In conclusion, results of this trial demonstrate a trend to a lower risk for relapse in patients treated with adjuvant 5-FU/LV for stage II colon cancer. However, in this study with limited power to detect small differences between the study arms, adjuvant chemotherapy failed to significantly improve DFS and OS

Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer

BACKGROUND: The role of adjuvant chemotherapy in patients with stage II colon cancer remains to be elucidated and its use varies between patients and institutions. Currently, clinical guidelines suggest discussing adjuvant chemotherapy for patients with high-risk stage II disease in the absence of conclusive randomized controlled trial data. In order to further investigate this relationship, the study aimed to determine whether an association exists between overall survival (OS) and adjuvant chemotherapy in patients stratified by age and pathological-risk features. METHODS: Data from the National Cancer Data Base (NCDB) was analyzed for demographics, tumor characteristics, management, and survival of patients with stage II colon cancer diagnosed from 1998-2006 with survival information through 2011. Pearson Chi-squared tests and binary logistic regression were used to analyze disease and demographic data. Survival analysis was performed with the Log-rank test and Cox proportional hazards regression modeling. Propensity score weighting was utilized to match cohorts. RESULTS: In 153,110 stage II colon cancer patients, predictors of receiving chemotherapy included age <65, male gender, non-Caucasian race, community treatment facility, non-Medicare insurance, and diagnosis before 2004. Improved and clinically relevant overall survival was associated with the receipt of adjuvant chemotherapy in all patient sub-groups regardless of high-risk tumor pathologic features (poor or undifferentiated histology, <12 lymph nodes evaluated, positive margins, or T4 histology), age, or chemotherapy regimen, even after adjustment for covariates and propensity score weighting (HR 0.76, p<0.001). There was not a difference in survival between single and multi-agent adjuvant chemotherapy regimens. CONCLUSION: In the largest group of stage II colon cancer patients evaluated to date, improved OS was associated with adjuvant chemotherapy regardless of treatment regimen, patient age, or high-risk pathologic risk features