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- Title
A phase II study of preoperative chemoradiation with tegafur-uracil plus leucovorin for locally advanced rectal cancer with pharmacogenetic analysis.
- Authors
Sun Young Kim; Ji Yeon Baek; Jae Hwan Oh; Sung Chan Park; Dae Kyung Sohn; Min Ju Kim; Hee Jin Chang; Sun-Young Kong; Dae Yong Kim; Kim, Sun Young; Baek, Ji Yeon; Oh, Jae Hwan; Park, Sung Chan; Sohn, Dae Kyung; Kim, Min Ju; Chang, Hee Jin; Kong, Sun-Young; Kim, Dae Yong
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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).<bold>Results: </bold>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).<bold>Conclusions: </bold>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.<bold>Trial Registration: </bold>ISRCTN11812525 , registered on 25 July 2016. Retrospectively registered.
- Subjects
RECTAL cancer treatment; COMBINATION drug therapy; URACIL; FOLINIC acid; CHEMORADIOTHERAPY; PREOPERATIVE care; PHARMACOGENOMICS; THERAPEUTICS; ANTINEOPLASTIC agents; CLINICAL trials; COMBINED modality therapy; COMPARATIVE studies; ENZYMES; FLUOROURACIL; GENETIC polymorphisms; GLYCOPROTEINS; HETEROCYCLIC compounds; RESEARCH methodology; MEDICAL cooperation; OXIDOREDUCTASES; RECTUM tumors; RESEARCH; TRANSFERASES; EVALUATION research; TREATMENT effectiveness; KAPLAN-Meier estimator; GENOTYPES
- Publication
Radiation Oncology, 2017, Vol 12, p1
- ISSN
1748-717X
- Publication type
journal article
- DOI
10.1186/s13014-017-0800-5