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TNFRSF1B A1466G genotype is predictive of clinical efficacy after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma.

ABSTRACT: BACKGROUND: Currently definitive 5-fluorouracil (5-FU)/cisplatin (CDDP) -based chemotherapy is recognized as one of the most promising treatments for esophageal cancer. A series of studies performed found genetic polymorphisms and the plasma concentration of 5-FU to be predictive of acute severe toxicities and clinical response. Genetic polymorphisms of tumor necrosis factor (TNF) -alpha and its surface receptors, TNFRSF1A and TNFRSF1B have been examined in terms of susceptibility to various cancers. In this study, genetic polymorphisms of TNFRSF1B gene were evaluated Japanese esophageal squamous cell carcinoma (ESCC) patients treated with the definitive 5-FU/CDDP-based chemoradiotherapy and their predictive values of prognosis or severe acute toxicities were assessed. METHODS: Forty-six patients with ESCC were treated with the definitive 5-FU/CDDP-based chemoradiotherapy, one course of which consisted of the continuous infusion of 5-FU for days 1-5 and 8-12, the infusion of CDDP on days 1 and 8, and the radiation at 2 Gy/day on days 1-5, 8-12, and 15-19, with a second course repeated after 2-week interval. Genetic polymorphisms of a TNF-alpha receptor TNFRSF1B gene were determined by a TaqMan(R) MGB probe-based polymerase chain reaction. RESULTS: The genotype of TNFSR1B A1466G, but not M196R/T587G or C1493T, was found to be predictive of clinical response, i.e., a complete response or not (p = 0.040). Clinical response was predicted by tumor size (p = 0,002), lymph node metastasis (p = 0.007), distant metastasis (p = 0.001) and disease stage (p < 0.001), but TNFRSF1B A1466G genotype was independent of these factors. CONCLUSIONS: Genetic polymorphism of TNFRSF1B A1466G was found to be predictive response in Japanese ESCC patients with a definitive 5-FU/CDDP-based chemoradiotherapy. Further clinical investigation with a large number of patients or experiments in vitro should be performed to assess the predictive value of TNFRSF1B A1466G genotype after chemoradiotherapy.

SUBMITTER: Kuwahara A

PROVIDER: S-EPMC2915971 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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TNFRSF1B A1466G genotype is predictive of clinical efficacy after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma.

Kuwahara Akiko A Yamamori Motohiro M Fujita Megumi M Okuno Tatsuya T Tamura Takao T Kadoyama Kaori K Okamura Noboru N Nakamura Tsutomu T Sakaeda Toshiyuki T

Journal of experimental & clinical cancer research : CR 20100720

<h4>Background</h4>Currently definitive 5-fluorouracil (5-FU)/cisplatin (CDDP) -based chemotherapy is recognized as one of the most promising treatments for esophageal cancer. A series of studies performed found genetic polymorphisms and the plasma concentration of 5-FU to be predictive of acute severe toxicities and clinical response. Genetic polymorphisms of tumor necrosis factor (TNF) -alpha and its surface receptors, TNFRSF1A and TNFRSF1B have been examined in terms of susceptibility to vari ...[more]

PMID: 20646319

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Project description:BACKGROUND:Reports have been accumulating that genetic properties are predictive of clinical response after and/or toxicity during cancer chemotherapy, but little information is available concerning effects on long-term survival. In this study, 49 Japanese patients with esophageal squamous cell carcinoma (ESCC) were followed up for 5 years after treatment with a definitive 5-fluorouracil (5-FU)/cisplatin (CDDP)-based chemoradiotherapy (CRT), and the effects of genotypes of vascular endothelial growth factor (VEGF) were retrospectively revaluated in terms of prediction of long-term survival. METHODS:A course consisted of the continuous infusion of 5-FU at 400 mg/m(2)/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m(2)/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week interval. The VEGF genotypes -1498T/C, -1154G/A, -634C/G, -7C/T, 936C/T, and 1612G/A were evaluated. RESULTS:The complete response (CR) rate was 46.9% (23/49). The 5-year survival rate was 42.9 % (21/49). There were 7 patients with a CR, but survival of less than 5 years. They died from myocardial infarction (N=1), sudden cardiac death after suffering from heart failure (N=1), acute myeloid leukemia that developed from myelodysplastic syndromes (N=1), factors not specified (N=2), oropharynx cancer (N=1), and tongue cancer (N=1). VEGF -634C/G had no effect on clinical response, but long-term survival depended on the genotype (p=0.033, Fisher's; p=0.038, Cochran-Armitage; p=0.079, Log-rank). The genotype frequency of 7 patients with a CR, but survival of less than 5 years was different from that for the other 42 patients (p=0.032, Fisher's). None of the other 5 genotypes evaluated affected either clinical response or survival. CONCLUSIONS:VEGF -634C/G is possibly predictive of long-term survival after treatment with a definitive 5-FU/CDDP-based CRT. Further clinical studies with a larger number of cases are needed to clarify the effects of this genotype.

Project description:PURPOSE:This trial aimed to assess the efficacy and safety of the paclitaxel plus fluorouracil regimen versus the cisplatin plus fluorouracil regimen in definitive concurrent chemoradiotherapy (dCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS:Patients with locally advanced ESCC were enrolled and randomly assigned to either the paclitaxel plus fluorouracil group or the cisplatin plus fluorouracil group. The patients in the paclitaxel plus fluorouracil group were treated with paclitaxel and fluorouracil one cycle per week in dCRT for five cycles followed by paclitaxel and fluorouracil one cycle per month in consolidation chemotherapy for two cycles. The patients in the cisplatin/5-fluorouracil group were treated with cisplatin and fluorouracil one cycle per month in dCRT for two cycles followed by two cycles in consolidation chemotherapy. The radiotherapy dose was 61.2 Gy delivered in 34 fractions. The primary end point was 3-year overall survival (OS). RESULTS:Four hundred thirty-six patients with ESCC in six centers were recruited at a 1:1 ratio between April 2012 and July 2015. The median follow-up of the surviving patients was 48.7 months (interquartile range, 42.6-60.9). The 3-year OS was 55.4% in the paclitaxel plus fluorouracil group and 51.8% in the cisplatin plus fluorouracil group (hazard ratio, 0.905 [95% CI, 0.698 to 1.172]; P = .448). The 3-year progression-free survival was also not significantly different between the paclitaxel plus fluorouracil group and the cisplatin plus fluorouracil group (43.7% v 45.5%, respectively; hazard ratio, 0.973 [95% CI, 0.762 to 1.243]; P = .828). Compared with the cisplatin plus fluorouracil group, the paclitaxel plus fluorouracil group had significantly lower incidences of acute grade 3 or higher anemia, thrombocytopenia, anorexia, nausea, vomiting, and fatigue (P < .05), but higher incidences of acute grade 3 or higher leukopenia, radiation dermatitis, and radiation pneumonitis (P < .05). CONCLUSION:The paclitaxel plus fluorouracil regimen did not significantly prolong the OS compared with the standard cisplatin plus fluorouracil regimen in dCRT in patients with locally advanced ESCC.

Dataset Information

TNFRSF1B A1466G genotype is predictive of clinical efficacy after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma.

Publications

TNFRSF1B A1466G genotype is predictive of clinical efficacy after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma.

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