Pharmacogenomic study of gemcitabine efficacy in patients with metastatic pancreatic cancer: A multicenter, prospective, observational cohort study (GENESECT study)

被引：1

作者：

Hatori, Masahiro ^{[1
,2
]}

Tsuji, Daiki ^{[2
]}

Suzuki, Kenichi ^{[3
]}

Yokokawa, Takashi ^{[1
]}

Kawakami, Kazuyoshi ^{[1
]}

Moriyama, Ryo ^{[2
]}

Osada-Tsuchiya, Marika ^{[2
]}

Otake, Aki ^{[2
]}

Nakao, Masahiko ^{[4
,5
]}

Yano, Takuya ^{[6
]}

Arakawa, Yuichiro ^{[7
]}

Matsuo, Keisuke ^{[8
]}

Ohashi, Yasukata ^{[9
]}

Sakata, Yasuhiko ^{[10
]}

Kogure, Yuki ^{[11
]}

Tamaki, Shinya ^{[12
]}

Wada, Atsushi ^{[13
]}

Taki, Yusuke ^{[14
]}

Sasahira, Naoki ^{[15
]}

Ishii, Hiroshi ^{[16
]}

Yamaguchi, Masakazu ^{[1
]}

Itoh, Kunihiko ^{[2
]}

机构：

[1] Japanese Fdn Canc Res, Canc Inst Hosp, Dept Pharm, Tokyo, Japan

[2] Univ Shizuoka, Sch Pharmaceut Sci, Dept Clin Pharmacol & Genet, 52-1 Yada,Suruga Ku, Shizuoka, Shizuoka 4228526, Japan

[3] Tokyo Univ Pharm & Life Sci, Sch Pharm, Dept Clin Pharmacol, Tokyo, Japan

[4] Osaka City Gen Hosp, Dept Pharm, Osaka, Japan

[5] Osaka City Gen Hosp, Clin Res Ctr, Osaka, Japan

[6] Sumitomo Besshi Hosp, Dept Pharm, Niihama, Japan

[7] Tochigi Canc Ctr, Dept Pharm, Utsunomiya, Japan

[8] Beppu Med Ctr, Dept Pharm, Beppu, Japan

[9] Natl Ctr Global Hlth & Med, Dept Pharm, Tokyo, Japan

[10] Hiroshima Citizens Hosp, Dept Pharm, Hiroshima, Japan

[11] Natl Ctr Higashi Hiroshima, Med Ctr, Dept Pharm, Higashihiroshima, Japan

[12] KKR Sapporo Med Ctr, Dept Pharm, Sapporo, Japan

[13] Kobe Minimally Invas Canc Ctr, Dept Pharm, Kobe, Japan

[14] Kikugawa Gen Hosp, Dept Pharm, Kikugawa, Japan

[15] Canc Inst Hosp, Dept Gastroenterol, Tokyo, Japan

[16] Chiba Canc Ctr, Div Gastroenterol, Tokyo, Japan

来源：

CANCER | 2024年 / 130卷 / 17期

关键词：

cyclooxygenase-2 (COX-2); gemcitabine; pancreatic cancer; pharmacogenomics; ribonucleotide reductase subunit 1 (RRM1); SINGLE NUCLEOTIDE POLYMORPHISMS; MESSENGER-RNA EXPRESSION; REDUCTASE SUBUNIT M2; CHEMOTHERAPY; SURVIVAL; ASSOCIATION; CA-19-9; ADENOCARCINOMA; RESISTANCE; DECREASE;

D O I：

10.1002/cncr.35343

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Genetic polymorphisms of molecules are known to cause individual differences in the therapeutic efficacy of anticancer drugs. However, to date, germline mutations (but not somatic mutations) for anticancer drugs have not been adequately studied. The objective of this study was to investigate the association between germline polymorphisms of gemcitabine metabolic and transporter genes with carbohydrate antigen 19-9 (CA 19-9) response (decrease >= 50% from the pretreatment level at 8 weeks) and overall survival (OS) in patients with metastatic pancreatic cancer who receive gemcitabine-based chemotherapy. Methods: This multicenter, prospective, observational study enrolled patients with metastatic pancreatic cancer patients who were receiving gemcitabine monotherapy or gemcitabine plus nanoparticle albumin-bound paclitaxel combination chemotherapy. Thirteen polymorphisms that may be involved in gemcitabine responsiveness were genotyped, and univariate and multivariate logistic regression analyses were used to determine the association of these genotypes with CA 19-9 response and OS. The significance level was set at 5%. Results: In total, 180 patients from 11 hospitals in Japan were registered, and 159 patients whose CA 19-9 response could be assessed were included in the final analysis. Patients who had a CA 19-9 response had significantly longer OS (372 vs. 241 days; p = .007). RRM1 2464A>G and RRM2 175T>G polymorphisms suggested a weak association with CA 19-9 response and OS, but it was not statistically significant. COX-2 -765G>C polymorphism did not significantly correlate with CA 19-9 response but was significantly associated with OS (hazard ratio, 2.031; p = .019). Conclusions: Genetic polymorphisms from the pharmacokinetics of gemcitabine did not indicate a significant association with efficacy, but COX-2 polymorphisms involved in tumor cell proliferation might affect OS.

引用

页码：2988 / 2999

页数：12

共 48 条

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