一项关于瑞舒伐他汀联合新辅助放化疗用于局部晚期直肠癌患者的随机II/III期试验。
A randomized phase II/III trial of rosuvastatin with neoadjuvant chemo-radiation in patients with locally advanced rectal cancer.
作者信息
Patil Prachi S, Saklani Avanish, Kumar Naveena A N, De'Souza Ashwin, Krishnatry Rahul, Khanvilkar Snehal, Kazi Mufaddal, Engineer Reena, Ostwal Vikas, Ramaswamy Anant, Bal Munita, Ranganathan Priya, Gupta Ekta, Galande Sanjeev
机构信息
Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India.
Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India.
出版信息
Front Oncol. 2025 Mar 19;15:1450602. doi: 10.3389/fonc.2025.1450602. eCollection 2025.
AIM
Statins have been shown to improve the possibility of a pathological complete response (pCR) in patients with locally advanced rectal cancer when given in combination with neo-adjuvant chemo-radiation (NACTRT) in observational studies. The primary objective of this phase II randomized controlled trial (RCT) is to determine the impact of rosuvastatin in improving pCR rates in patients with locally advanced rectal cancer who are undergoing NACTRT. The secondary objectives are to compare adverse events, postoperative morbidity and mortality, disease-free survival (DFS), and overall survival in the two arms and to identify potential prognostic and predictive factors determining outcomes. If the study is positive, we plan to proceed to a phase III RCT with 3-year DFS as the primary endpoint.
METHODS
This is a prospective, randomized, open-label phase II/III study. The phase II study has a sample size of 316 patients (158 in each arm) to be accrued over 3 years to have 288 evaluable patients. The standard arm will receive NACTRT while the intervention group will receive 20 mg rosuvastatin orally once daily along with NACTRT for 6 weeks followed by rosuvastatin alone for 6-10 weeks until surgery. All patients will be reviewed after repeat imaging by a multidisciplinary tumor board at 12-16 weeks after starting NACTRT and operable patients will be planned for surgery. The pathological response rate, tumor regression grade (TRG), and post-surgical complications will be recorded.
CONCLUSION
The addition of rosuvastatin to NACTRT may improve the oncological outcomes by increasing the likelihood of pCR in patients with locally advanced rectal cancer undergoing NACTRT. This would be a low-cost, low-risk intervention that could potentially lead to the refinement of strategies, such as "watch and wait", in a select subgroup of patients.
CLINICAL TRIAL REGISTRATION
Clinical Trials Registry of India, identifier CTRI/2018/11/016459.
目的
观察性研究表明，他汀类药物与新辅助放化疗（NACTRT）联合使用时，可提高局部晚期直肠癌患者病理完全缓解（pCR）的可能性。这项II期随机对照试验（RCT）的主要目的是确定瑞舒伐他汀对接受NACTRT的局部晚期直肠癌患者pCR率的影响。次要目的是比较两组的不良事件、术后发病率和死亡率、无病生存期（DFS）和总生存期，并确定决定预后的潜在预后因素和预测因素。如果该研究结果呈阳性，我们计划开展一项以3年DFS为主要终点的III期RCT。
方法
这是一项前瞻性、随机、开放标签的II/III期研究。II期研究的样本量为316例患者（每组158例），将在3年内招募，以获得288例可评估患者。标准组将接受NACTRT，而干预组将在接受NACTRT的同时，每天口服一次20mg瑞舒伐他汀，持续6周，随后单独服用瑞舒伐他汀6 - 10周，直至手术。所有患者在开始NACTRT后12 - 16周经多学科肿瘤委员会重复影像学检查后进行评估，可手术患者将安排手术。记录病理缓解率、肿瘤退缩分级（TRG）和术后并发症。
结论
在NACTRT基础上加用瑞舒伐他汀可能通过增加接受NACTRT的局部晚期直肠癌患者pCR的可能性来改善肿瘤学结局。这将是一种低成本、低风险的干预措施，可能会使“观察等待”等策略在特定亚组患者中得到优化。
临床试验注册
印度临床试验注册中心，标识符CTRI/2018/11/016459。
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