Prolonged survival in a patient with BRCA2 associated metastatic pancreatic cancer after exposure to camptothecin: a case report and review of literature
Prolonged survival in a patient with BRCA2 associated metastatic pancreatic cancer after exposure to camptothecin: a case report and review of literature
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DOI：
10.1097/cad.0b013e32832b511e
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发表时间：
2009-08-01
影响因子：
2.3
通讯作者：
Saif, Muhammad Wasif
中科院分区：
文献类型：
--
作者：
James, Edward;Waldron-Lynch, Maeve G.;Saif, Muhammad Wasif
肿瘤抑制基因BRCA1和BRCA2的种系突变已被证明可以预测携带这些基因的人患乳腺癌和卵巢癌的终身风险大幅增加。许多研究表明，与这些突变相关的第三种最常见的癌症是胰腺癌。在BRCA2突变的胰腺细胞系中，有证据表明交联剂对丝裂霉素C(MMC)有体内治疗作用。我们介绍了第一位服用伊立替康的患者，伊立替康是一种拓扑异构酶I类毒物，单独给药，然后与西妥昔单抗联合使用，可以延长患者的生存时间。我们的病人在71岁时出现前列腺癌和胰腺癌的双重诊断，背景是有明显的癌症家族史。在基因测试中，他被发现有常见的德系犹太人BRCA2突变，6174delT。到目前为止，他已经接受了22个周期的多西他赛、卡培他滨和吉西替宾，然后是单药伊立替康，每3周一次，共27个周期，然后在第28个周期中每周增加一次西妥昔单抗。随后，他的病情又稳定了13个月。他没有突变KRAS。丝裂霉素C和奥沙利铂随后在进展时被引入。他目前的治疗是MMC加伊立替康，因为奥沙利铂因过敏反应而被移除。这位患者在首次诊断后四年半(56个月)的东部合作肿瘤组表现状态稳定。DNA拓扑异构酶是负责调节DNA拓扑结构的核酶。它们参与复制、转录和重组过程中的基本DNA交易。BRCA2缺失的人类细胞缺乏通过同源重组修复双链断裂和DNA交联链的能力。拓扑异构酶I的活性毒物包括喜树碱的衍生物。我们的病例是第一个临床证据表明BRCA2相关的胰腺癌对喜树碱-11的敏感性增加和拓扑异构酶I的松弛活性降低。这一病例表明，转移性胰腺癌和BRCA2突变的患者可能患有生物学上对化疗更敏感的疾病，因此尽管疾病预后不佳，但仍可延长生存期。抗癌药物20：634-638(C)2009沃尔特斯·克鲁沃健康垂直酒吧Lippincott Williams&Wilkins。
Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 have been proven to predict a drastically increased lifetime risk of breast and ovarian cancers in the individuals who carry them. A number of studies have shown that the third most common cancer associated with these mutations is pancreatic cancer. There is evidence of in vivo therapeutic response to the cross-linking agents; such as mitomycin C (MMC) in BRCA2 mutated pancreatic cell lines. We present the 'first patient' who achieved a prolonged survival on irinotecan, a topoisomerase I poison, administered alone and then in combination with cetuximab. Our patient presented at the age of 71 years with a dual diagnosis of prostate carcinoma and pancreatic carcinoma on the background of a significant family history of cancer. On genetic testing, he was found to have the common Ashkenazi Jewish BRCA2 mutation, 6174delT. To date, he has received 22 cycles of docetaxel, capecitabine, and gemcitibine followed by single agent irinotecan every 3 weeks for 27 cycles, and then weekly cetuximab was added to the regimen at cycle 28. His disease then remained stable for an additional 13 months. He did not have mutated KRAS. MMC and oxaliplatin was then introduced upon progression. His current treatment is MMC plus irinotecan as oxaliplatin was removed because of a hypersensitivity reaction. This patient is stable with an Eastern Cooperative Oncology Group performance status of 0, four and a half years (56 months) after his initial diagnosis. DNA topoisomerases are nuclear enzymes responsible for the regulation of DNA topology. They are involved in basic DNA transactions during replication, transcription, and recombination. BRCA2-deficient human cells are deficient in the repair of double-strand breaks and DNA cross-links through homologous recombination. Active poisons of topoisomerase I include derivatives of camptothecin. Our case is the first clinical piece of evidence that demonstrates an increased sensitivity to camptothecin-11 and a reduced topoisomerase I relaxation activity in BRCA2 associated pancreatic cancer. This case shows that patients with metastatic pancreatic carcinoma and BRCA2 mutations may have disease that is biologically more chemosensitive and consequently prolong survival despite prognostically unfavorable disease. Anti-Cancer Drugs 20:634-638 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.