A prospective feasibility study of uracil-tegafur and leucovorin as adjuvant chemotherapy for patients aged ≥ 80 years after curative resection of colorectal cancer, the HiSCO-03 study.

PURPOSE: There is no consensus on the safety and effectiveness of adjuvant chemotherapy for patients with stage III colorectal cancer (CRC) aged ≥ 80 years. We conducted a prospective multi-institutional phase II study of uracil-tegafur and leucovorin (UFT/LV) as adjuvant chemotherapy in this population. PATIENTS AND METHODS: Patients with stage III CRC aged ≥ 80 years who underwent curative resection were enrolled. Eligible patients received UFT/LV therapy (UFT, 300 mg/m2 per day as tegafur; LV, 75 mg/day on days 1-28, every 35 days for five courses). Primary endpoint was feasibility, and secondary endpoints were safety and relative dose intensity. RESULTS: Sixty-nine patients were enrolled between 2013 and 2021. Of the 69 patients, 65 were included in the analysis. There were 32 males and 33 females with a median age of 82 years (range 80-88 years). In the primary endpoint, administration completion rate was 67.3% (95% confidence interval 54.9-77.6%), and the lower limit of the 95% confidence interval was below the threshold of 60%. 21 patients discontinued treatment because of adverse events (AEs) and refused treatment. The median relative dose intensities were 84% (range 4-100%) for UFT, and 100% (range 4-100%) for LV. Incidence of grade three or higher AEs were neutropenia (1.5%), aspartate transaminase elevation (3%), alanine transaminase elevation (1.5%), oral mucositis (3%), anemia (1.5%), and diarrhea (4.6%). CONCLUSIONS: The indications for adjuvant UFT/LV therapy for elderly CRC aged ≥ 80 years were considered limited. It is necessary to clarify the background of patients in whom drug administration is discontinued and investigate their impact on long-term prognosis.

Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study.

BACKGROUND: Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC). Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine. PATIENTS AND METHODS: Patients with completely resected stage III and high-risk stage II CRC aged ≥20 years were eligible. Patients were treated with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) for 3 months followed by capecitabine (2,500 mg/m2 on days 1-14 every 3 weeks) for 3 months. Primary end points were frequency and the grade of oxaliplatin-induced neurotoxicity as evaluated using the physician-based Common Terminology Criteria for Adverse Events version 4.0 (CTCAE) grading and the patient-based scale, self-reported Patient Neurotoxicity Questionnaire. RESULTS: Ninety-one patients were enrolled and 86 patients assessed. Eighty-four percent of patients completed the planned oxaliplatin-based therapy for 3 months, and 63% of patients completed all treatments for the full 6 months. Overall incidences of grade 3 or 4 peripheral sensory or motor neuropathy according to the CTCAE were 3.5% and 1.2%, respectively. Regarding the peripheral sensory neuropathy, the proportion of Patient Neurotoxicity Questionnaire (grade C-E) and CTCAE (grade 2-4) at months 1.5/3/6 were 11.3/22.1/29.4% and 5.3/4.4/11.3%, respectively (Spearman correlation coefficient: 0.47). CONCLUSION: A sequential approach to adjuvant chemotherapy with 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine was tolerated by patients and associated with a low incidence of neuropathy.