Dataset Information

Adjuvant Oral Uracil-Tegafur with Leucovorin for Colorectal Cancer Liver Metastases: A Randomized Controlled Trial.

ABSTRACT:

Background

The high recurrence rate after surgery for colorectal cancer liver metastasis (CLM) remains a crucial problem. The aim of this trial was to evaluate the efficacy of adjuvant therapy with uracil-tegafur and leucovorin (UFT/LV).

Methods

In the multicenter, open-label, phase III trial, patients undergoing curative resection of CLM were randomly assigned in a 1:1 ratio to either the UFT/LV group or surgery alone group. The UFT/LV group orally received 5 cycles of adjuvant UFT/LV (UFT 300mg/m2 and LV 75mg/day for 28 days followed by a 7-day rest per cycle). The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included overall survival (OS).

Results

Between February 2004 and December 2010, 180 patients (90 in each group) were enrolled into the study. Of these, 3 patients (2 in the UFT/LV group and 1 in the surgery alone group) were excluded from the efficacy analysis. Median follow-up was 4.76 (range, 0.15-9.84) years. The RFS rate at 3 years was higher in the UFT/LV group (38.6%, n = 88) than in the surgery alone group (32.3%, n = 89). The median RFS in the UFT/LV and surgery alone groups were 1.45 years and 0.70 years, respectively. UFT/LV significantly prolonged the RFS compared with surgery alone with the hazard ratio of 0.56 (95% confidence interval, 0.38-0.83; P = 0.003). The hazard ratio for death of the UFT/LV group against the surgery alone group was not significant (0.80; 95% confidence interval, 0.48-1.35; P = 0.409).

Conclusion

Adjuvant therapy with UFT/LV effectively prolongs RFS after hepatic resection for CLM and can be recommended as an alternative choice.

Trial registration

UMIN Clinical Trials Registry C000000013.

SUBMITTER: Hasegawa K

PROVIDER: S-EPMC5010179 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Adjuvant Oral Uracil-Tegafur with Leucovorin for Colorectal Cancer Liver Metastases: A Randomized Controlled Trial.

Hasegawa Kiyoshi K Saiura Akio A Takayama Tadatoshi T Miyagawa Shinichi S Yamamoto Junji J Ijichi Masayoshi M Teruya Masanori M Yoshimi Fuyo F Kawasaki Seiji S Koyama Hiroto H Oba Masaru M Takahashi Michiro M Mizunuma Nobuyuki N Matsuyama Yutaka Y Watanabe Toshiaki T Makuuchi Masatoshi M Kokudo Norihiro N

PloS one 20160902 9

<h4>Background</h4>The high recurrence rate after surgery for colorectal cancer liver metastasis (CLM) remains a crucial problem. The aim of this trial was to evaluate the efficacy of adjuvant therapy with uracil-tegafur and leucovorin (UFT/LV).<h4>Methods</h4>In the multicenter, open-label, phase III trial, patients undergoing curative resection of CLM were randomly assigned in a 1:1 ratio to either the UFT/LV group or surgery alone group. The UFT/LV group orally received 5 cycles of adjuvant U ...[more]

PMID: 27588959

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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.

Project description:Resection of colorectal liver metastases (CRLM) is a potential curative treatment for patients with metastatic colorectal cancer (mCRC) with liver-limited disease (LLD). Although long-term survival improved considerably within the last decades, high recurrence rates of 50-75% after resection remain a major challenge.Tecemotide (L-BLP25) is an antigen-specific cancer vaccine inducing immunity against mucin-1 (MUC1). The LICC trial aimed to improve survival in patients with mCRC after R0/R1 resection of CRLM. LICC was a binational, randomized, double-blind, placebo-controlled, multicenter phase 2 study including patients with R0/R1 resected CRLM without evidence of metastatic disease outside the liver. Co-primary endpoints were recurrence-free survival (RFS) and 3-year overall survival (OS) rate, secondary endpoints were RFS and OS in subgroups with different MUC1 expression and safety. In total, 121 patients were 2:1 randomized between Oct 2011 and Dec 2014to receive tecemotide (N=79) or placebo (N=42). Baseline characteristics were well balanced. Median RFS was 6.1 months (95% CI 4.5-8.9) and 11.4 months (95% CI 3.7-21.2) (P = .1754), 3-year OS rate 69.1% and 79.1%, median OS 62.8 months and not reached in the tecemotide vs. placebo arm (P = .2141), respectively. Cox regression models revealed no dependence of RFS or OS on MUC1 expression. The most common tecemotide-related grade 3/4 adverse events were diarrhea, injection site reaction, intestinal perforation, peritonitis and tinnitus (1.3% each). The LICC trial failed to meet its primary endpoints of significantly improving RFS and OS with tecemotide. However, both arms showed unexpectedly long OS. MUC1 expression was not associated with outcome.EudraCT No: 2011-000218-20Clinical Trial Information: NCT01462513Financial Support: Merck KGaA, Darmstadt, Germany.AbbreviationsAE: adverse event; CP: cyclophosphamide; CRC: colorectal cancer; CT: computed tomography; ECOG: Eastern Cooperative Oncology Group; FU: follow-up; HR: hazard ratio; IHC: immunohistochemical staining; ITT: intention-to-treat; DSMB: Data Safety Monitoring Board; LLD: liver-limited disease; mCRC: metastatic colorectal cancer; MPLA: monophosphoryl lipid; AMRI: magnetic resonance imaging; MUC1: mucin 1; NA: not applicable; NCI-CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events; NS: normal saline; NSCLC: non-small-cell lung carcinoma; OS: overall surviva; lPP: per protocol; RAS: Rat sarcoma; RFS: recurrence-free survival; TEAE: treatment-emergent adverse event; UICC: Union for International Cancer Control; US: ultrasound; vs.: versus.

Dataset Information

Adjuvant Oral Uracil-Tegafur with Leucovorin for Colorectal Cancer Liver Metastases: A Randomized Controlled Trial.

Background

Methods

Results

Conclusion

Trial registration

Publications

Adjuvant Oral Uracil-Tegafur with Leucovorin for Colorectal Cancer Liver Metastases: A Randomized Controlled Trial.

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