NCT03448549

SOX Versus XELOX as Adjuvant Chemotherapy for Stage III Colorectal Cancer Patients

A Prospective Randomized Controlled Trial to Compare Oxaliplatin Combined With S-1 (SOX) Versus Oxaliplatin With Capecitabine (XELOX) as Adjuvant Chemotherapy for Stage III Colorectal Cancer Patients

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,191 (estimated)
• Sponsor: Peking University Cancer Hospital & Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Fluorouracil combined with oxaliplatin are routinely recommended to patients with pathological stage III (p-stage III) colorectal cancer, leading to significant improvement of 5-year disease-free survival and overall survival (approximately 3.4% -4.2%) by by international guidelines such as the National Cancer Comprehensive Network. The Considerable proportion of patients suffer with hand-foot syndrome due to capecitabine as commonly prescribed. Meanwhile as another agent of fluorouracil, tegafur，gimeracil and oteracil potassium (short for TGOP) has been shown with similar effect and less adverse reaction. This study was designed to investigate the short-term and long-term safety and efficacy of TGOP-OX and XELOX regimens in colorectal cancer p-stage III patients who undergo curative surgery and adjuvant chemotherapy, and to explore the compliance and quality of life in patients treated with TGOP-OX regime.

Detailed description

In patients with pathological stage III colorectal cancer, capecitabine combined with oxaliplatin, as routinely prescribed for adjuvant chemotherapy prolongs the patient's 5-year disease-free survival and overall survival (about 3.4% -4.2%) and is therefore recommended by the National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO) and other international guidelines. Accumulating evidence has shown that a majority of chemotherapy-related side effects were caused by capecitabine, especially in certain patients with hand-foot syndrome lasting a long time. Tegafur，gimeracil and oteracil potassium (TGOP), as another fluorouracil, was shown to be equally effective for colorectal cancer patients as adjuvant chemotherapy. The results of two multicenter randomized controlled trials (Adjuvant Chemotherapy Trial of S-1 for Colon Cancer and Adjuvant Chemotherapy Trial of S-1 for RectalCancer) reported at the American Society of Clinical Oncology (ASCO) 2015 suggested that patients with stage III colorectal cancer treated with tegafur，gimeracil and oteracil potassium (TGOP) instead of capecitabine for adjuvant chemotherapy resulted in comparative effects (5 year Disease free survival: 61.7% -70.2%; 5-year Overall survival: 66.4% -86.0%) with significant lower 3/4 degrees of adverse events. As a compound combined with tegafur, gimeracil and oteracil potassium in a molar ratio of 1: 0.4: 1, it plays an anti-tumor effect as 5-Fu precursor drug, metabolized by liver cytochrome enzyme (P450) system into 5-Fu with less toxicity. The addition of tegafur improves the anti-tumor activity by raising its oral absorption. Gimeracil, as a potent and reversible inhibitor of dihydropyrimidine dehydrogenase (DPD enzyme), largely increases the concentration of 5-Fu in blood and tumor tissue, meanwhile reduces the 5-Fu no active metabolite fluoride-β-alanine (F-β-Ala) production, leading to the decrease of cardiovascular and neural toxicity and the incidence of hand-foot syndrome . Oteracil potassium specifically inhibits the intestinal mucosal cells within the orotate phosphoribosyl transferase (OPRT enzyme), blocking 5-Fu phosphorylation, reducing the digestive tract mucosal damage, thereby lowering the digestive tract toxicity. Colorectal cancer patients who undergo curative surgery, are enrolled in this study, and randomized into TGOP combined with oxaliplatin (TGOP-OX) and capecitabine combined with oxaliplatin (XELOX) groups. The aim of the study is to confirm that the efficacy of TGOP-OX group as adjuvant chemotherapy is not inferior to that of the XELOX group. Adverse reactions will be systemically collected based on CTCAE 4.0 criteria for each cycle. The quality of life was assessed by the European Cancer Research Organization questionnaires. Patients will undergo close follow-up according to the NCCN recommendation. Minimum follow-up period is designed as 3 years, and each endpoint will be evaluated as each check-point.

Conditions

• Colorectal Cancer Stage III
• Adjuvant Chemotherapy

Interventions

Type	Name	Description
DRUG	Oxaliplatin	adjuvant chemotherapy
DRUG	Tegafur，gimeracil and oteracil potassium	adjuvant chemotherapy
DRUG	Xeloda	adjuvant chemotherapy

Timeline

• Start date: 2018-01-01
• Primary completion: 2021-01-01
• Completion: 2024-01-01
• First posted: 2018-02-28
• Last updated: 2020-03-06

Locations

1 site across 1 country: China