Department of Innovation and Clinical Research Center, Japan Agency for Medical Research and Development, 21F Yomiuri shinbun Bldg. 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan.
Department of Pharmacy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Cancer Chemother Pharmacol. 2020 Aug;86(2):315-324. doi: 10.1007/s00280-020-04118-9. Epub 2020 Aug 3.
The combination of docetaxel, cisplatin and 5-fluorouracil (DCF) is a newly developed chemotherapy regimen for esophageal cancer. Severe neutropenia is dose-limiting toxicity of docetaxel and it is well known to be frequently occurred during DCF chemotherapy. This study aimed to investigate the relationship between severe neutropenia and genetic polymorphisms in patients treated with preoperative DCF chemotherapy.
A total of 158 patients were investigated for their absolute neutrophil count (ANC) within the first cycle of DCF chemotherapy at the National Cancer Center (NCC) Hospital East. DNA samples obtained from the NCC Biobank Registry were used for the analysis of nine genetic polymorphisms related to docetaxel pharmacokinetics. These genotypes were evaluated for their association with severe neutropenia, and further their risk factors were examined using a multivariate logistic regression.
A total 81 (51.3%) patients developed severe neutropenia. Multivariate analysis revealed that age (OR 1.054; CI 1.008-1.102, P = 0.022), baseline ANC (OR 1.019; CI 1.002-1.037, P = 0.030), ABCB1 3435C>T (OR 2.191; CI 1.087-4.417, P = 0.028) and ABCC2 *+9383C>G (OR 2.342; CI 1.108-4.948, P = 0.026) were significant risk factors for severe neutropenia development. The results from this study showed that age, ANC, ABCB1 3435C>T, and ABCC2 *+9383 G>C increased the incidence of severe neutropenia with the number of identified risk factors.
In addition to age and baseline ANC, ABCB1 3435C>T and ABCC2 *+9383C>G were identified as independent predictors for severe neutropenia in esophageal cancer patients treated with DCF chemotherapy.
多西他赛、顺铂和 5-氟尿嘧啶（DCF）的联合方案是一种新开发的用于治疗食管癌的化疗方案。多西他赛的剂量限制毒性是严重中性粒细胞减少症，并且在 DCF 化疗期间经常发生。本研究旨在探讨接受术前 DCF 化疗的患者中严重中性粒细胞减少症与遗传多态性之间的关系。
在国立癌症中心（NCC）医院东部，对 158 例患者在 DCF 化疗的第一个周期内的绝对中性粒细胞计数（ANC）进行了调查。从 NCC 生物银行登记处获得的 DNA 样本用于分析与多西他赛药代动力学相关的 9 种遗传多态性。评估这些基因型与严重中性粒细胞减少症的相关性，并使用多变量逻辑回归进一步检查其危险因素。
共有 81 例（51.3%）患者发生严重中性粒细胞减少症。多变量分析显示，年龄（OR 1.054；95%CI 1.008-1.102，P=0.022）、基线 ANC（OR 1.019；95%CI 1.002-1.037，P=0.030）、ABCB1 3435C>T（OR 2.191；95%CI 1.087-4.417，P=0.028）和 ABCC2*+9383C>G（OR 2.342；95%CI 1.108-4.948，P=0.026）是严重中性粒细胞减少症发生的显著危险因素。本研究结果表明，年龄、ANC、ABCB1 3435C>T 和 ABCC2*+9383G>C 增加了严重中性粒细胞减少症的发生率，并且随着危险因素数量的增加而增加。
除了年龄和基线 ANC 外，ABCB1 3435C>T 和 ABCC2*+9383C>G 被确定为接受 DCF 化疗的食管癌患者严重中性粒细胞减少症的独立预测因子。
