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.

Clinicopathological Outcomes in Patients With Locally Advanced Rectal Cancer Undergoing Preoperative Short-Versus Long-course Chemoradiotherapy With Delayed Surgery.

BACKGROUND/AIM: We aimed to compare the clinicopathological outcomes in patients with locally advanced rectal cancer after short- or long-course concurrent chemoradiotherapy (CCRT) followed by delayed surgery. PATIENTS AND METHODS: The records of 94 patients with cT3-4N0-2M0 rectal cancer who received CCRT between 2010 and 2017 were reviewed. Short-course radiotherapy (RT) was delivered with a median total dose of 25 Gy in five fractions (n=27), and long-course RT was delivered with a median total dose of 50.4 Gy in 28 fractions (n=67). The following concurrent chemotherapy regimens were administered: 5-fluorouracil plus leucovorin in 58 and capecitabine in 24; in 12 cases agents were unknown. The median interval between CCRT and surgery was 8 weeks. Adjuvant chemotherapy was administered after surgery in 80 patients (5-fluorouracil plus leucovorin, n=54; capecitabine, n=9; other, n=14; and unknown, n=3). Propensity-score matching analysis was conducted. RESULTS: The median follow-up duration was 4.3 years. There were no statistically significant differences between the short- and long-course RT groups in sphincter preservation (85.2% vs. 92.5%, p=0.478), pathological complete remission (18.5% vs. 14.9%, p=0.905), downstaging (44.4% vs. 26.9%, p=0.159), and negative circumferential resection margin (92.6% vs. 89.6%, p=0.947) rates. No differences were found in survival outcomes between the short- and long-course groups at 3 years (overall survival: 91.8% vs. 88.1%, p=0.790; disease-free survival, 75.2% vs. 72.5%, p=0.420; locoregional relapse-free survival, 90.5% vs. 98.4%, p=0.180; and distant metastasis-free survival, 79.6% vs. 73.5%, p=0.490). Similar results were observed after PSM. CONCLUSION: Clinically, short-course CCRT may be a feasible alternative to long-course CCRT in patients with locally advanced rectal cancer.