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

被引：7

作者：

Kim, Sun Young ^{[2
,3
]}

Baek, Ji Yeon ^{[2
]}

Oh, Jae Hwan ^{[2
]}

Park, Sung Chan ^{[2
]}

Sohn, Dae Kyung ^{[2
]}

Kim, Min Ju ^{[2
]}

Chang, Hee Jin ^{[2
]}

Kong, Sun-Young ^{[1
]}

Kim, Dae Yong ^{[2
]}

机构：

[1] Natl Canc Ctr, Res Inst & Hosp, Dept Lab Med, 323 Ilsan ro, Goyang 10408, Gyeonggi, South Korea

[2] Natl Canc Ctr, Res Inst & Hosp, Ctr Colorectal Canc, Ilsan ro 323, Goyang 10408, Gyeonggi, South Korea

[3] Univ Ulsan, Asan Med Ctr, Coll Med, Dept Oncol, 88 Olymp ro 43-gil, Seoul 05505, South Korea

来源：

RADIATION ONCOLOGY | 2017年 / 12卷

关键词：

Rectal neoplasms; Chemoradiotherapy; Tegafur; Uridine monophosphate synthetase; SURGICAL ADJUVANT BREAST; NEOADJUVANT CHEMORADIATION; COLORECTAL-CANCER; RANDOMIZED-TRIAL; ORAL LEUCOVORIN; STAGE-II; OXALIPLATIN; CAPECITABINE; CHEMORADIOTHERAPY; THERAPY;

D O I：

10.1186/s13014-017-0800-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: This study aimed to evaluate the efficacy of a high dose of oral tegafur-uracil (400 mg/m(2)) 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/m(2)/day and leucovorin 90 mg/m(2)/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/m(2)/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.

引用

页数：9