Dataset Information

Safety analysis of two different regimens of uracil-tegafur plus leucovorin as adjuvant chemotherapy for high-risk stage II and III colon cancer in a phase III trial comparing 6 with 18 months of treatment: JFMC33-0502 trial.

ABSTRACT:

Purpose

The JFMC33-0502 trial is a phase III clinical study designed to determine the most appropriate duration of postoperative adjuvant chemotherapy with uracil-tegafur (UFT) plus leucovorin in patients with stage IIB or III colon cancer. We report the interim results of preplanned safety analyses.

Methods

Patients with stage IIB or III colon cancer who had undergone curative resection were randomly assigned to receive UFT (300 mg/m(2)) plus leucovorin (75 mg/day) for 6 months (control group, 4 weeks of treatment followed by a 1-week rest, five courses) or for 18 months (study group, 5 days of treatment followed by a 2-day rest, 15 courses). Treatment status and safety were evaluated.

Results

A total of 1,071 patients were enrolled, and 1,063 were included in safety analyses. Treatment completion rate at 6 months was 74.0 % in the control group and 76.7 % in the study group. Treatment completion rate in the study group at 18 months was 56.0 %. The overall incidence of adverse events (AEs) was 75.3 % in the control group and 77.6 % in the study group. The incidences of grade 3 or higher AEs were low in both groups. During the first 6 months, the incidences of the subjective AEs were significantly lower in the study group.

Conclusions

Oral UFT plus leucovorin given by either dosage schedule is a very safe regimen for adjuvant chemotherapy. In particular, 5 days of treatment followed by a 2-day rest was a useful treatment option from the viewpoint of toxicity even when given for longer than 6 months.

SUBMITTER: Tsuchiya T

PROVIDER: S-EPMC4032639 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Shikha VermaBackground Systemic fluoropyrimidines, both oral and intravenous, are an integral part of colorectal cancer (CRC) management. They can be administered either with curative or palliative intent. Objectives This article examines the literature to analyze the efficacy and safety of the oral fixed-dose combination of uracil and tegafur (UFT)/leucovorin (LV) compared with other fluoropyrimidine agents, with an intention to implement the findings into the current treatment algorithms for CRC. Methods An exhaustive systematic literature search was performed for prospective studies using PUBMED, Cochrane Library, and EMBASE database. Studies which met eligibility criteria were shortlisted and grouped into chemotherapy given for curative or palliative intent. Results Eight trials were shortlisted involving 4,486 patients for the analysis. There was no difference between UFT/LV and other fluoropyrimidines in the primary endpoints-disease-free survival (hazard ratio [HR] 1.01; 95% confidence interval [CI] 0.90-.15; p = 0.81) and progression-free survival (HR 0.87; 95% CI 0.66-.66; p = 0.35) for curative and palliative intent CRC patients, respectively. In secondary analyses, there was no significant difference observed between UFT and other fluoropyrimidines in overall survival in CRC patients with curative intent (HR 1.04; 95% CI 0.88-1.23; p = 0.63) and palliative intent (HR 1.02; 95% CI 0.97-1.06; p = 0.42) . In the safety analysis, we found significantly lesser patients on UFT/LV had stomatitis/mucositis (odds ratio [OR] 0.20; 95% CI 0.05-0.85; p = 0.03), fever (OR 0.46; 95% CI 0.29-0.71; p < 0.001), infection (OR 0.42; 95% CI 0.24-0.74; p < 0.01), leukopenia (OR 0.04; 95% CI 0.00-0.95; p = 0.05), febrile neutropenia (OR 0.03; 95% CI 0.00-0.24; p = 0.001), and thrombocytopenia (OR 0.14; 95% CI 0.02-0.79; p = 0.03) compared with other fluoropyrimidines. Conclusion Oral UFT/LV is equally efficacious to other fluoropyrimidines, especially intravenous 5-fluorouracil, in the management of early as well as advanced CRC patients. Importantly, UFT/LV has a superior safety profile compared with other fluoropyrimidines in terms of both hematological and nonhematological adverse events.