Hisanaga Nomura1,2, Daiki Tsuji3, Shohei Ueno3, Takashi Kojima4, Satoshi Fujii5,6, Tomonori Yano7, Hiroyuki Daiko8, Ken Demachi9, Kunihiko Itoh3, Toshikatsu Kawasaki9. 1. Department of Data Science National Cancer Center Hospital East, Kashiwa, Chiba, Japan. hnomura@east.ncc.go.jp. 2. Department of Pharmacy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. hnomura@east.ncc.go.jp. 3. Department of Clinical Pharmacology & Genetics, University of Shizuoka, Shizuoka, Shizuoka, Japan. 4. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. 5. Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. 6. Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Chiba, Kashiwa, Japan. 7. Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. 8. Department of Esophageal Surgery, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan. 9. Department of Pharmacy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Abstract
PURPOSE: Docetaxel, cisplatin, and 5-fluorouracil (DCF) have high response rates, but severe neutropenia is frequently observed. The occurrence of neutropenia is associated with high histological response in solid tumors, and it might be associated with tumor shrinkage after DCF therapy. This study aimed to determine the genetic polymorphisms involved in the clinical response to preoperative DCF therapy in esophageal cancer patients. METHODS: We included 56 patients with measurable lesions who received preoperative DCF therapy for esophageal cancer. Twenty-one genetic polymorphisms were analyzed, and univariate logistic regression analysis was used to evaluate the association between genetic polymorphisms and tumor shrinkage. A multivariate logistic regression analysis adjusted for T category and tumor location and a univariate analysis for potential genetic factors with P values < 0.05 were performed to explore the predictive factors and to estimate odds ratios and their 95% confidence intervals. RESULTS: No patient achieved a complete response, whereas 20 patients achieved a partial response, 31 patients had stable disease, and 5 patients had progressive disease. Although no association was found between pharmacokinetic-related gene polymorphisms, XRCC3 rs17997944 was extracted as the only genetic factor that affected tumor shrinkage (P = 0.033) by univariate analysis. The multivariate analysis adjusted for T category and tumor site also showed that XRCC3 rs1799794: AA was a predictive factor that affected tumor shrinkage (odds ratio, 0.243; 95% confidence interval, 0.065-0.914; P = 0.036). CONLUSIONS: XRCC3 rs1799794, which is involved in homologous recombination, is a genetic factor that affects clinical responses to DCF therapy.
PURPOSE: Docetaxel, cisplatin, and 5-fluorouracil (DCF) have high response rates, but severe neutropenia is frequently observed. The occurrence of neutropenia is associated with high histological response in solid tumors, and it might be associated with tumor shrinkage after DCF therapy. This study aimed to determine the genetic polymorphisms involved in the clinical response to preoperative DCF therapy in esophageal cancer patients. METHODS: We included 56 patients with measurable lesions who received preoperative DCF therapy for esophageal cancer. Twenty-one genetic polymorphisms were analyzed, and univariate logistic regression analysis was used to evaluate the association between genetic polymorphisms and tumor shrinkage. A multivariate logistic regression analysis adjusted for T category and tumor location and a univariate analysis for potential genetic factors with P values < 0.05 were performed to explore the predictive factors and to estimate odds ratios and their 95% confidence intervals. RESULTS: No patient achieved a complete response, whereas 20 patients achieved a partial response, 31 patients had stable disease, and 5 patients had progressive disease. Although no association was found between pharmacokinetic-related gene polymorphisms, XRCC3 rs17997944 was extracted as the only genetic factor that affected tumor shrinkage (P = 0.033) by univariate analysis. The multivariate analysis adjusted for T category and tumor site also showed that XRCC3 rs1799794: AA was a predictive factor that affected tumor shrinkage (odds ratio, 0.243; 95% confidence interval, 0.065-0.914; P = 0.036). CONLUSIONS: XRCC3 rs1799794, which is involved in homologous recombination, is a genetic factor that affects clinical responses to DCF therapy.
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