Association Between ABCC2 -24C>T and Nab-Paclitaxel-induced Peripheral Neuropathy in Japanese Patients With Pancreatic Cancer.

IF 1.6 4区医学 Q4 ONCOLOGY

Anticancer research Pub Date : 2024-11-01 DOI:10.21873/anticanres.17326

Hana Nakayama, Hiroo Ishida, Masanori Iidaka, Shoko Kato, Kei Nakatani, Akihiro Nakayama, Toshihiro Noguchi, Shigetoshi Nishihara, Shu Oikawa, Tomono Usami, Yuta Mitsui, Y U Ishii, Hirokazu Toshima, Kouji Kobayashi, Remi Murase, Natsumi Matsumoto, Kosuke Suzuki, Ken Shimada, Hitoshi Yoshida, Ken-Ichi Fujita

{"title":"Association Between ABCC2 -24C>T and Nab-Paclitaxel-induced Peripheral Neuropathy in Japanese Patients With Pancreatic Cancer.","authors":"Hana Nakayama, Hiroo Ishida, Masanori Iidaka, Shoko Kato, Kei Nakatani, Akihiro Nakayama, Toshihiro Noguchi, Shigetoshi Nishihara, Shu Oikawa, Tomono Usami, Yuta Mitsui, Y U Ishii, Hirokazu Toshima, Kouji Kobayashi, Remi Murase, Natsumi Matsumoto, Kosuke Suzuki, Ken Shimada, Hitoshi Yoshida, Ken-Ichi Fujita","doi":"10.21873/anticanres.17326","DOIUrl":null,"url":null,"abstract":"Background/aim: Nab-paclitaxel is used to treat patients with pancreatic cancer. However, it frequently induces peripheral neuropathy. Notably, pharmacokinetic factors may be associated with neuropathic symptoms as the onset depends on the cumulative dose. Therefore, we prospectively examined the association between the cumulative dose of nab-paclitaxel at the onset of peripheral neuropathy and polymorphisms of hepatic transporter genes.Patients and methods: Patients with pancreatic cancer receiving nab-paclitaxel (125 mg/m2) and gemcitabine (1,000 mg/m2) were enrolled. Peripheral neuropathy was assessed using the Common Terminology Criteria for Adverse Events (CTCAE), Patient-Reported Outcomes CTCAE (PRO-CTCAE), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), every 2-12 weeks, and every 4 weeks thereafter. solute carrier organic anion transporter family member 1B1 (SLCO1B1) 521T>C, 388A>G; SLCO1B3 rs11045585; ATP-binding cassette transporters, subfamily B, member 1 (ABCB1) 1236C>T, 2677G>T/A, 3435C>T; ABCC1 rs2644983; ABCC2 24C>T; and ABCG2 421C>A were analyzed by direct sequencing. Correlations between transporter genotypes and cumulative dose at symptom onset were assessed using Kaplan-Meier and log-rank tests.Results: In total, 25 patients were enrolled. The lowest median cumulative dose for nab-paclitaxel at peripheral neuropathy onset using PRO-CTCAE was 593 mg. By CTCAE it was 800 mg, and by FACT/GOG-Ntx it was 1,090 mg (p<0.0001). At symptom onset, patients with ABCC2 -24C/T genotype had received a significantly lower median cumulative dose by PRO-CTCAE (540 mg) than those with C/C (720 mg) (p=0.0188). However, the other polymorphisms studied were not associated with symptoms.Conclusion: Herein, we found for the first time that ABCC2 -24C/T genotype was significantly associated with the onset of nab-paclitaxel-induced peripheral neuropathy detected with PRO-CTCAE.","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"5023-5033"},"PeriodicalIF":1.6000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anticancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21873/anticanres.17326","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background/aim: Nab-paclitaxel is used to treat patients with pancreatic cancer. However, it frequently induces peripheral neuropathy. Notably, pharmacokinetic factors may be associated with neuropathic symptoms as the onset depends on the cumulative dose. Therefore, we prospectively examined the association between the cumulative dose of nab-paclitaxel at the onset of peripheral neuropathy and polymorphisms of hepatic transporter genes.

Patients and methods: Patients with pancreatic cancer receiving nab-paclitaxel (125 mg/m²) and gemcitabine (1,000 mg/m²) were enrolled. Peripheral neuropathy was assessed using the Common Terminology Criteria for Adverse Events (CTCAE), Patient-Reported Outcomes CTCAE (PRO-CTCAE), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), every 2-12 weeks, and every 4 weeks thereafter. solute carrier organic anion transporter family member 1B1 (SLCO1B1) 521T>C, 388A>G; SLCO1B3 rs11045585; ATP-binding cassette transporters, subfamily B, member 1 (ABCB1) 1236C>T, 2677G>T/A, 3435C>T; ABCC1 rs2644983; ABCC2 24C>T; and ABCG2 421C>A were analyzed by direct sequencing. Correlations between transporter genotypes and cumulative dose at symptom onset were assessed using Kaplan-Meier and log-rank tests.

Results: In total, 25 patients were enrolled. The lowest median cumulative dose for nab-paclitaxel at peripheral neuropathy onset using PRO-CTCAE was 593 mg. By CTCAE it was 800 mg, and by FACT/GOG-Ntx it was 1,090 mg (p<0.0001). At symptom onset, patients with ABCC2 -24C/T genotype had received a significantly lower median cumulative dose by PRO-CTCAE (540 mg) than those with C/C (720 mg) (p=0.0188). However, the other polymorphisms studied were not associated with symptoms.

Conclusion: Herein, we found for the first time that ABCC2 -24C/T genotype was significantly associated with the onset of nab-paclitaxel-induced peripheral neuropathy detected with PRO-CTCAE.

查看原文本刊更多论文

日本胰腺癌患者 ABCC2 -24C>T 与纳布-紫杉醇诱发的周围神经病变之间的关系

背景/目的：纳布紫杉醇用于治疗胰腺癌患者。然而，它经常诱发周围神经病变。值得注意的是，药代动力学因素可能与神经病理性症状有关，因为发病与累积剂量有关。因此，我们前瞻性地研究了外周神经病变发生时纳布-紫杉醇的累积剂量与肝脏转运体基因多态性之间的关系：纳入接受纳布-紫杉醇（125 mg/m2）和吉西他滨（1,000 mg/m2）治疗的胰腺癌患者。采用不良事件通用术语标准（CTCAE）、患者报告结果CTCAE（PRO-CTCAE）和癌症治疗功能评估/妇科肿瘤组-神经毒性（FACT/GOG-Ntx）评估外周神经病变，每2-12周评估一次，此后每4周评估一次。通过直接测序分析了溶质载体有机阴离子转运体家族成员 1B1 (SLCO1B1) 521T>C、388A>G；SLCO1B3 rs11045585；ATP 结合盒转运体 B 亚家族成员 1 (ABCB1) 1236C>T、2677G>T/A、3435C>T；ABCC1 rs2644983；ABCC2 24C>T；以及 ABCG2 421C>A。采用 Kaplan-Meier 检验和对数秩检验评估了转运体基因型与发病时累积剂量之间的相关性：结果：共有 25 名患者入选。根据PRO-CTCAE，外周神经病发时纳布-紫杉醇的最低中位累积剂量为593毫克。根据 CTCAE，中位数为 800 毫克，根据 FACT/GOG-Ntx 中位数为 1,090 毫克（pConclusion）：在此，我们首次发现 ABCC2 -24C/T 基因型与使用 PRO-CTCAE 检测到的纳布-紫杉醇诱导的周围神经病变的发生有显著相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.