School of Medicine and Dentistry, Griffith University, Gold Coast, Australia.
School of Environment and Sciences, Griffith University, Nathan, Australia.
J Cancer Res Clin Oncol. 2023 Aug;149(10):8117-8129. doi: 10.1007/s00432-023-04735-w. Epub 2023 Apr 8.
Pancreatic ductal adenocarcinoma (PDAC) remains a common and difficult cancer to treat. Surgical resection and chemotherapy are standard of care and clinical outcomes remain poor. Oncolytic adenoviruses are a unique approach to the treatment of this challenging cancer, aiming to overcome the features of this disease that pose the key obstacles to standard therapies. This paper provides a detailed review of the clinical trials of conditionally-replicative adenoviruses in pancreatic cancer to date, with a brief summary of the past preclinical literature and future prospects of this therapy.
MEDLINE, Embase, and clinicaltrials.gov were searched from inception to December 23rd 2022 for clinical trials of conditionally-replicative adenoviruses used in patients with pancreatic ductal adenocarcinoma. Primary features for review included patient demographics, treatment protocol including dose and administration route, adverse events, patient responses and survival rates.
The six published clinical trials suggest that objective clinical responses can be achieved with a tolerable level of side effects, even at high viral doses. The more clinically adaptable intravenous route of administration also appears to be as well tolerated as the more challenging intratumoural injections.
Published clinical trials provide data of the safety and some signs of oncolytic activity of conditionally-replicative adenoviruses in patients with pancreatic cancer. Importantly, on the latest trials, the easier intravenous route of administration seems to be well tolerated and safe, providing the opportunity for further clinical evaluation. It is hoped that the ongoing clinical trials will yield more promising results of this therapeutic approach against a currently intractable disease.
胰腺导管腺癌（PDAC）仍然是一种常见且难以治疗的癌症。手术切除和化疗是标准的治疗方法，但临床疗效仍然不佳。溶瘤腺病毒是治疗这种具有挑战性癌症的一种独特方法，旨在克服这种疾病的特征，这些特征是标准疗法的主要障碍。本文详细回顾了迄今为止溶瘤腺病毒在胰腺癌中的临床试验，并简要总结了过去的临床前文献和该疗法的未来前景。
从建库到 2022 年 12 月 23 日，我们在 MEDLINE、Embase 和 clinicaltrials.gov 上搜索了用于治疗胰腺导管腺癌患者的条件复制腺病毒的临床试验。审查的主要特征包括患者人口统计学、治疗方案（包括剂量和给药途径）、不良反应、患者反应和生存率。
已发表的六项临床试验表明，即使使用高病毒剂量，也可以通过可耐受的副作用水平获得客观的临床反应。更具临床适应性的静脉给药途径似乎与更具挑战性的肿瘤内注射一样耐受良好。
已发表的临床试验提供了关于条件复制腺病毒在胰腺癌患者中的安全性和一些溶瘤活性的临床数据。重要的是，在最新的试验中，更容易的静脉给药途径似乎耐受良好且安全，为进一步的临床评估提供了机会。希望正在进行的临床试验能为这种针对目前难以治疗的疾病的治疗方法带来更有希望的结果。
