A multicenter, open-label, single-arm, phase II study evaluated the efficacy and safety of capecitabine plus oxaliplatin (XELOX) as adjuvant therapy in Japanese patients with operated stage III colon cancer. The primary endpoint was the 3-year disease-free survival (DFS). The study also monitored the incidence of peripheral sensory neuropathy (PSN) associated with the treatment.
Study Design and Patient Population
The trial enrolled patients aged 20 years or older with histologically confirmed stage III colon adenocarcinoma who had undergone colectomy with D2 or D3 lymph node dissection and achieved curative resection. Key inclusion criteria included an ECOG performance status of 0 or 1 and adequate organ function. Patients with pre-existing grade > 1 PSN, uncontrolled medical conditions, or other malignancies were excluded. A total of 195 patients were recruited for this study.
Treatment Protocol
The XELOX regimen consisted of intravenous oxaliplatin (130 mg/m2) on day 1, followed by oral capecitabine (2000 mg/m2/day) in two divided doses for 14 days, administered in a 3-week cycle for eight cycles (24 weeks). Treatment was initiated within 8 weeks of surgery. Dose modifications were implemented based on observed adverse events, including PSN, hand-foot syndrome (HFS), and hematological toxicities.
Efficacy and Safety Outcomes
The primary endpoint was the 3-year DFS. Tumor assessments using abdominal computed tomography, ultrasonography, and chest radiography were performed at baseline and every 6 months for 5 years after the primary surgery. Tests for carcinoembryonic antigen and carbohydrate antigen 19–9 were conducted every 3 months for the first 3 years and every 6 months thereafter. The Kaplan–Meier method was used to evaluate the 3-year DFS and 5-year overall survival.
If the following criteria for the initiation of treatment were not met on the day of or the day before the start of each course, treatment was postponed for a maximum of 42 days: neutrophil count ≥ 1500/mm3, platelet count ≥ 75,000/mm3, PSN persistent grade ≥ 1, grade ≥ 1 hand-foot syndrome (HFS), and other parameters at the attending physician’s discretion.
Dose Modifications for Adverse Events
Dose modifications were based on the most severe adverse events observed during the previous treatment cycle. If any of the following adverse events occurred (except PSN and HFS), oxaliplatin and capecitabine doses were reduced to 100 or 85 mg/m2 and 1500 or 1000 mg/m2, respectively: grade ≥ 2 leukopenia, neutropenia, or thrombocytopenia, and any other grade ≥ 3 hematological or grade ≥ 2 non-hematological adverse events. Oxaliplatin dose was reduced to 100 mg/m2 or 85 mg/m2 if the patient developed persistent grade 2 PSN or grade 3 PSN, respectively. Oxaliplatin was discontinued if the patient developed a second occurrence of grade 2/3 or 4 PSN and if grade ≥ 3 adverse events occurred. Capecitabine monotherapy was permitted in patients who refused or discontinued oxaliplatin due to drug-induced PSN. Capecitabine dose was adjusted for adverse events of grade ≥ 2 HFS. At the first occurrence of grade ≥ 2 HFS, treatment was interrupted and resumed at a reduced dose of 1500 mg/m2 after resolution to grade 1 or better. For second occurrences of grade ≥ 2 HFS, treatment was interrupted and resumed at a reduced dose of 1000 mg/m2 after resolution to grade 1 or better.
