Dataset Information

A phase II study of preoperative chemoradiation with tegafur-uracil plus leucovorin for locally advanced rectal cancer with pharmacogenetic analysis.

ABSTRACT:

Background

This study aimed to evaluate the efficacy of a high dose of oral tegafur-uracil (400 mg/m²) plus leucovorin with preoperative chemoradiation of locally advanced rectal cancer and to explore the impact of polymorphisms of cytochrome P 2A6 (CYP2A6), uridine monophosphate synthetase (UMPS), and ATP-binding cassette B1 (ABCB1) on clinical outcome.

Methods

Patients with cT3 or cT4 rectal cancer were enrolled and were given tegafur-uracil 400 mg/m²/day and leucovorin 90 mg/m²/day for 7 days a week during preoperative chemoradiation (50.4 Gy/28 fractions) in this phase II trial. Primary endpoint was pathologic complete response rate, and the secondary endpoint was to explore the association between clinical outcomes and genetic polymorphisms CYP2A6 (*4, *7, *9 and *10), UMPS G638C, and three ABCB1 genotypes (C1236T, C3435T, and G2677T).

Results

Ninety-one patients were given study treatment, and 90 underwent surgery. Pathologic complete response was noted in 10 patients (11.1%). There was no grade 4 or 5 toxicity; 20 (22.0%) experienced grade 3 toxicities, including diarrhea (10, 11.0%), abdominal pain (2, 2.2%), and anemia (2, 2.2%). Relapse-free survival and overall survival at 5 years were 88.6% and 94.2%, respectively. Patients with the UMPS 638 CC genotype experienced significantly more frequent grade 2 or 3 diarrhea (p for trend = 0.018).

Conclusions

Preoperative chemoradiation with tegafur-uracil 400 mg/m²/day with leucovorin was feasible, but did not meet the expected pathologic complete response rate. The UMPS 638 CC genotype might be a candidate biomarker predicting toxicity in patients receiving tegafur-uracil/leucovorin-based preoperative chemoradiation for locally advanced rectal cancer.

Trial registration

ISRCTN11812525 , registered on 25 July 2016. Retrospectively registered.

SUBMITTER: Kim SY

PROVIDER: S-EPMC5369180 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Publications

A phase II study of preoperative chemoradiation with tegafur-uracil plus leucovorin for locally advanced rectal cancer with pharmacogenetic analysis.

Kim Sun Young SY Baek Ji Yeon JY Oh Jae Hwan JH Park Sung Chan SC Sohn Dae Kyung DK Kim Min Ju MJ Chang Hee Jin HJ Kong Sun-Young SY Kim Dae Yong DY

Radiation oncology (London, England) 20170327 1

<h4>Background</h4>This study aimed to evaluate the efficacy of a high dose of oral tegafur-uracil (400 mg/m<sup>2</sup>) plus leucovorin with preoperative chemoradiation of locally advanced rectal cancer and to explore the impact of polymorphisms of cytochrome P 2A6 (CYP2A6), uridine monophosphate synthetase (UMPS), and ATP-binding cassette B1 (ABCB1) on clinical outcome.<h4>Methods</h4>Patients with cT3 or cT4 rectal cancer were enrolled and were given tegafur-uracil 400 mg/m<sup>2</sup>/day a ...[more]

PMID: 28347333

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Dataset Information

A phase II study of preoperative chemoradiation with tegafur-uracil plus leucovorin for locally advanced rectal cancer with pharmacogenetic analysis.

Background

Methods

Results

Conclusions

Trial registration

Publications

A phase II study of preoperative chemoradiation with tegafur-uracil plus leucovorin for locally advanced rectal cancer with pharmacogenetic analysis.

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