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Relevance of pharmacogenetic polymorphisms with response to docetaxel, cisplatin, and 5-fluorouracil chemotherapy in esophageal cancer

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Summary

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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Data availability

The datasets during and analyzed during the current study available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Data Science National Cancer Center Hospital East, Kashiwa, Chiba, Japan

    Hisanaga Nomura

  2. Department of Pharmacy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan

    Hisanaga Nomura, Ken Demachi & Toshikatsu Kawasaki

  3. Department of Clinical Pharmacology & Genetics, University of Shizuoka, Shizuoka, Shizuoka, Japan

    Daiki Tsuji, Shohei Ueno & Kunihiko Itoh

  4. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan

    Takashi Kojima

  5. Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Satoshi Fujii

  6. Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Chiba, Kashiwa, Japan

    Satoshi Fujii

  7. Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan

    Tomonori Yano

  8. Department of Esophageal Surgery, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan

    Hiroyuki Daiko

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Contributions

Conception and design were performed by HN, DT, TaKo, HD, and SF. Acquisition of data was carried out by HN, KD, HD, and TaKo. The analysis of SNPs were DT, SU, and KI. Statistical analysis and interpretation of the data were carried out by DT and SU. Drafting of the article was carried out by NH, DT, TaKo, ToKa, and SF. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hisanaga Nomura.

Ethics declarations

Ethics approval and consent to participate

The study protocol was approved by the institutional review board of the NCC, Japan in March 2017 (2016–384). These patients were consented to be used the clinical information and DNA sample in the National Cancer Center (NCC) Biobank Registry. The study design is displayed on the website for the National Cancer Center Hospital East, providing the relatives of deceased patients the opportunity to decline participation in the current study.

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All authors agree to publish.

Research involving Human Participants and/or Animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

All patients provided their written informed consent to allow the use of their clinical information and DNA samples, which are available in the NCC Biobank Registry.

Disclosure of potential conflicts of interest

Takashi Kojima received honoraria from Ono and MSD and research funding from Ono, MSD, Taiho, Chugai, Shionogi and Palexel. Tomoaki Yano received honoraria from Olympus, Meijiseika pharma and research funding from Olympus, Fujifirm, HOYA PENTAX, Rakuten Medical, SHIMADZU and Tokyo Giken. All other authors declare no potential conflicts of interest.

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Nomura, H., Tsuji, D., Ueno, S. et al. Relevance of pharmacogenetic polymorphisms with response to docetaxel, cisplatin, and 5-fluorouracil chemotherapy in esophageal cancer. Invest New Drugs 40, 420–429 (2022). https://doi.org/10.1007/s10637-021-01199-y

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