A pilot study of chlorambucil in pre-treated metastatic pancreatic adenocarcinoma patients bearing germline BRCA or other DNA damage repair system variants

IF 2.8 2区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pancreatology Pub Date : 2024-11-01 DOI:10.1016/j.pan.2024.09.006
Catia Carconi , Carlo Bosi , Mario Scartozzi , Massimiliano Cergnul , Marika Cinausero , Luca Faloppi , Ingrid Garajova , Sara Lonardi , Irene Pecora , Laura Pisanu , Rosella Spadi , Andrea Spallanzani , Umberto Peretti , Marina Macchini , Giulia Orsi , Michele Reni
{"title":"A pilot study of chlorambucil in pre-treated metastatic pancreatic adenocarcinoma patients bearing germline BRCA or other DNA damage repair system variants","authors":"Catia Carconi ,&nbsp;Carlo Bosi ,&nbsp;Mario Scartozzi ,&nbsp;Massimiliano Cergnul ,&nbsp;Marika Cinausero ,&nbsp;Luca Faloppi ,&nbsp;Ingrid Garajova ,&nbsp;Sara Lonardi ,&nbsp;Irene Pecora ,&nbsp;Laura Pisanu ,&nbsp;Rosella Spadi ,&nbsp;Andrea Spallanzani ,&nbsp;Umberto Peretti ,&nbsp;Marina Macchini ,&nbsp;Giulia Orsi ,&nbsp;Michele Reni","doi":"10.1016/j.pan.2024.09.006","DOIUrl":null,"url":null,"abstract":"<div><h3>Backgorund</h3><div>Pancreatic adenocarcinoma remains a malignancy with a grim prognosis and scarce personalized treatment options. Pathogenic variants of DNA damage repair (DDR) genes are emerging as molecular targets, as they confer a higher sensitivity to DNA-damaging agents. This study aimed at assessing the activity of chlorambucil as salvage therapy in metastatic pancreatic cancer patients bearing a germline pathogenetic variant or variant of uncertain significance on a DDR-related gene.</div></div><div><h3>Methods</h3><div>Platinum-pretreated metastatic pancreatic cancer patients harbouring a germline variant on a DDR gene received chlorambucil at a daily oral dose of 6 mg/m<sup>2</sup> for 42 every 56 days for the first cycle and for 14 every 28 days for the following cycles, until disease progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival rate (PFS-6). Median progression-free survival (PFS) and overall survival (OS) were secondarily described.</div></div><div><h3>Results</h3><div>Twenty patients were enrolled between December 2020 and September 2022. PFS-6 was 5%, median PFS and OS were 1.6 months and 3.0 months, respectively. Grade-3 adverse events were observed in 25% of patients, while no Grade-4 toxicity was reported.</div></div><div><h3>Conclusions</h3><div>Single agent chlorambucil did not show sufficient signal of activity to warrant its further investigation in metastatic pancreatic cancer patients bearing a DDR-related germline alteration.</div></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":"24 7","pages":"Pages 1066-1072"},"PeriodicalIF":2.8000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pancreatology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1424390324007361","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Backgorund

Pancreatic adenocarcinoma remains a malignancy with a grim prognosis and scarce personalized treatment options. Pathogenic variants of DNA damage repair (DDR) genes are emerging as molecular targets, as they confer a higher sensitivity to DNA-damaging agents. This study aimed at assessing the activity of chlorambucil as salvage therapy in metastatic pancreatic cancer patients bearing a germline pathogenetic variant or variant of uncertain significance on a DDR-related gene.

Methods

Platinum-pretreated metastatic pancreatic cancer patients harbouring a germline variant on a DDR gene received chlorambucil at a daily oral dose of 6 mg/m2 for 42 every 56 days for the first cycle and for 14 every 28 days for the following cycles, until disease progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival rate (PFS-6). Median progression-free survival (PFS) and overall survival (OS) were secondarily described.

Results

Twenty patients were enrolled between December 2020 and September 2022. PFS-6 was 5%, median PFS and OS were 1.6 months and 3.0 months, respectively. Grade-3 adverse events were observed in 25% of patients, while no Grade-4 toxicity was reported.

Conclusions

Single agent chlorambucil did not show sufficient signal of activity to warrant its further investigation in metastatic pancreatic cancer patients bearing a DDR-related germline alteration.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
对携带生殖系 BRCA 或其他 DNA 损伤修复系统变异的预处理转移性胰腺癌患者进行氯霉素试点研究
胰腺腺癌仍然是一种预后严重、个性化治疗方案匮乏的恶性肿瘤。DNA损伤修复(DDR)基因的致病变异正在成为分子靶点,因为它们对DNA损伤药物具有更高的敏感性。本研究旨在评估氯霉素作为挽救疗法对带有DDR相关基因种系致病变异或意义不确定变异的转移性胰腺癌患者的活性。
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 去求助
来源期刊
Pancreatology
Pancreatology 医学-胃肠肝病学
CiteScore
7.20
自引率
5.60%
发文量
194
审稿时长
44 days
期刊介绍: Pancreatology is the official journal of the International Association of Pancreatology (IAP), the European Pancreatic Club (EPC) and several national societies and study groups around the world. Dedicated to the understanding and treatment of exocrine as well as endocrine pancreatic disease, this multidisciplinary periodical publishes original basic, translational and clinical pancreatic research from a range of fields including gastroenterology, oncology, surgery, pharmacology, cellular and molecular biology as well as endocrinology, immunology and epidemiology. Readers can expect to gain new insights into pancreatic physiology and into the pathogenesis, diagnosis, therapeutic approaches and prognosis of pancreatic diseases. The journal features original articles, case reports, consensus guidelines and topical, cutting edge reviews, thus representing a source of valuable, novel information for clinical and basic researchers alike.
期刊最新文献
Tailoring endoscopy for infected pancreatic necrosis: DEN or PEN or combined? Early prediction of post-pancreatectomy acute pancreatitis after pancreaticoduodenectomy based on serum C-reactive protein. Letter re: Outcomes of percutaneous endoscopic versus endoscopic transmural necrosectomy for necrotizing pancreatitis. No definite associations between opioid doses and severity of acute pancreatitis - Results from a multicentre international prospective study. Patient-derived organoids from pancreatic cancer after pancreatectomy: Feasibility and organoid take rate in treatment-naïve periampullary tumors.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1