mFOLFIRINOX versus mFOLFOX 6 as adjuvant treatment for high-risk stage III colon cancer - the FROST trial: study protocol for a multicenter, randomized controlled, phase II trial.

BACKGROUND: High-risk stage III colon cancer has a considerably poorer prognosis than stage II and low-risk stage III colon cancers. Nevertheless, most guidelines recommend similar adjuvant treatment approaches for all these stages despite the dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis with intensive adjuvant treatment. Given the the proven efficacy of triplet chemotherapy in metastatic colorectal cancer treatment, the goal of this study is to evaluate the oncologic efficacy and safety of mFOLFIRINOX in comparison to those of the current standard of care, mFOLFOX 6, as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer after radical resection. METHODS: This multicenter, randomized (1:1), open-label, phase II trial will assess and compare the effectiveness and toxicity of mFOLFIRINOX and mFOLFOX 6 in patients with high-risk stage III colon cancer after radical resection. The goal of the trial is to enroll 312 eligible patients, from 11 institutes, aged between 20 and 70 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or between 70 and 75 with an ECOG performance status of 0. Patients will be randomized into two arms - Arm A, the experimental arm, and Arm B, the reference arm - and will receive 12 cycles of mFOLFIRINOX and mFOLFOX 6 every 2 weeks, respectively. The primary endpoint of this study is the 3-year disease-free survival, and secondary endpoints include the 3-year overall survival and treatment toxicity. DISCUSSION: The Frost trial would help determine the oncologic efficacy and safety of adjuvant triplet chemotherapy for high-risk stage III colon cancers and ultimately improve prognoses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05179889, registered on 17 December 2021.

The impact of mechanical bowel preparation in elective colorectal surgery: a propensity score matching analysis.

PURPOSE: To evaluate the influence of preoperative mechanical bowel preparation (MBP) based on the occurrence of anastomosis leakage, surgical site infection (SSI), and severity of surgical complication when performing elective colorectal surgery. MATERIALS AND METHODS: MBP and non-MBP patients were matched using propensity score. The outcomes were evaluated according to tumor location such as right- (n=84) and left-sided colon (n=50) and rectum (n=100). In the non-MBP group, patients with right-sided colon cancer did not receive any preparation, and patients with both left-sided colon and rectal cancers were given one rectal enema before surgery. RESULTS: In the right-sided colon surgery, there was no anastomosis leakage. SSI occurred in 2 (4.8%) and 4 patients (9.5%) in the non-MBP and MBP groups, respectively. In the left-sided colon cancer surgery, there was one anastomosis leakage (4.0%) in each group. SSI occurred in none in the rectal enema group and in 2 patients (8.0%) in the MBP group. In the rectal cancer surgery, there were 5 anastomosis leakages (10.0%) in the rectal enema group and 2 (4.0%) in the MBP group. SSI occurred in 3 patients (6.0%) in each groups. Severe surgical complications (Grade III, IV, or V) based on Dindo-Clavien classification, occurred in 7 patients (14.0%) in the rectal enema group and 1 patient (2.0%) in the MBP group (p=0.03). CONCLUSION: Right- and left-sided colon cancer surgery can be performed safely without MBP. In rectal cancer surgery, rectal enema only before surgery seems to be dangerous because of the higher rate of severe postoperative complications.

Comparative analysis of thymidylate synthase at the protein, mRNA, and DNA levels as prognostic markers in colorectal adenocarcinoma.

BACKGROUND AND OBJECTIVES: To determine the best routinely available molecular methodology for assessing thymidylate synthase (TS) as a prognostic marker in colorectal adenocarcinoma, TS was examined at the protein, mRNA, and DNA levels. Direct comparison of these routinely available assays has not been systematically studied across a large colon cancer patient cohort with long-term follow-up. METHODS: We studied 150 surgically resected colorectal adenocarcinoma patients who received postoperative 5-Fluorouracil (5-FU) chemotherapy. TS immuunohistochemistry and real-time quantitative RT-PCR and PCR genotyping on patient-matched tumor and normal tissues were performed. RESULTS: Surprisingly, mRNA values in normal tissue varied from 0.11 to 62.0 and significantly correlated with mRNA values of matched tumor tissues. Although higher tumor/normal ratios of mRNA expression trended toward poorer patient survival, neither this nor TS immunohistochemistry results were statistically significant predictors. TS tumor genotype was generally concordant with matched normal tissues. Further, the 2R/3R genotype of 5'-TSER was significantly correlated with poorer patient survival (P = 0.0249) and was also an independent prognostic marker on multivariate analysis. CONCLUSION: TS genotyping on paraffin-embedded fixed tissues proved to be the most useful method for prediction of outcome of 5-FU treatment in patients with colorectal adenocarcinoma.