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A phase II study of preoperative chemoradiation with tegafur-uracil plus leucovorin for locally advanced rectal cancer with pharmacogenetic analysis.
- Source :
- Radiation Oncology; 3/27/2017, Vol. 12, p1-9, 9p
- Publication Year :
- 2017
-
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. [ABSTRACT FROM AUTHOR]
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1748717X
- Volume :
- 12
- Database :
- Complementary Index
- Journal :
- Radiation Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 122269038
- Full Text :
- https://doi.org/10.1186/s13014-017-0800-5