A randomized phase II/III trial of rosuvastatin with neoadjuvant chemo-radiation in patients with locally advanced rectal cancer

AimStatins 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...

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Main Authors: Prachi S. Patil, Avanish Saklani, Naveena A. N. Kumar, Ashwin De’Souza, Rahul Krishnatry, Snehal Khanvilkar, Mufaddal Kazi, Reena Engineer, Vikas Ostwal, Anant Ramaswamy, Munita Bal, Priya Ranganathan, Ekta Gupta, Sanjeev Galande
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Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1450602/full
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author Prachi S. Patil
Avanish Saklani
Naveena A. N. Kumar
Ashwin De’Souza
Rahul Krishnatry
Snehal Khanvilkar
Mufaddal Kazi
Reena Engineer
Vikas Ostwal
Anant Ramaswamy
Munita Bal
Priya Ranganathan
Ekta Gupta
Ekta Gupta
Sanjeev Galande
Sanjeev Galande
author_facet Prachi S. Patil
Avanish Saklani
Naveena A. N. Kumar
Ashwin De’Souza
Rahul Krishnatry
Snehal Khanvilkar
Mufaddal Kazi
Reena Engineer
Vikas Ostwal
Anant Ramaswamy
Munita Bal
Priya Ranganathan
Ekta Gupta
Ekta Gupta
Sanjeev Galande
Sanjeev Galande
author_sort Prachi S. Patil
collection DOAJ
description AimStatins 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.MethodsThis 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.ConclusionThe 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 registrationClinical Trials Registry of India, identifier CTRI/2018/11/016459.
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spelling doaj-art-aca083e604f84687bbd5d8be29d728cf2025-08-20T03:41:46ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-03-011510.3389/fonc.2025.14506021450602A randomized phase II/III trial of rosuvastatin with neoadjuvant chemo-radiation in patients with locally advanced rectal cancerPrachi S. Patil0Avanish Saklani1Naveena A. N. Kumar2Ashwin De’Souza3Rahul Krishnatry4Snehal Khanvilkar5Mufaddal Kazi6Reena Engineer7Vikas Ostwal8Anant Ramaswamy9Munita Bal10Priya Ranganathan11Ekta Gupta12Ekta Gupta13Sanjeev Galande14Sanjeev Galande15Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, IndiaDepartment of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, IndiaDepartment of Surgical Oncology, Manipal Comprehensive Cancer Care Center, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, IndiaDepartment of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, IndiaDepartment of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, IndiaTata Memorial Hospital, Homi Bhabha National Institute, Mumbai, IndiaDepartment of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, IndiaDepartment of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, IndiaDepartment of Medical Oncology, Tata Memorial Hospital, Homi Bhabha national Institute, Mumbai, IndiaDepartment of Medical Oncology, Tata Memorial Hospital, Homi Bhabha national Institute, Mumbai, IndiaDepartment of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, IndiaDepartment of Anaesthesiology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, IndiaLaboratory of Chromatin Biology and Epigenetics, Department of Biology, Indian Institute of Science Education and Research, Pune, India0Centre of Excellence in Epigenetics, Department of Life Sciences, Shiv Nadar Institution of Eminence, Delhi, IndiaLaboratory of Chromatin Biology and Epigenetics, Department of Biology, Indian Institute of Science Education and Research, Pune, India0Centre of Excellence in Epigenetics, Department of Life Sciences, Shiv Nadar Institution of Eminence, Delhi, IndiaAimStatins 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.MethodsThis 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.ConclusionThe 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 registrationClinical Trials Registry of India, identifier CTRI/2018/11/016459.https://www.frontiersin.org/articles/10.3389/fonc.2025.1450602/fullrosuvastatinpathological complete responseneoadjuvant chemoradiationrectal cancerdrug repurposing
spellingShingle Prachi S. Patil
Avanish Saklani
Naveena A. N. Kumar
Ashwin De’Souza
Rahul Krishnatry
Snehal Khanvilkar
Mufaddal Kazi
Reena Engineer
Vikas Ostwal
Anant Ramaswamy
Munita Bal
Priya Ranganathan
Ekta Gupta
Ekta Gupta
Sanjeev Galande
Sanjeev Galande
A randomized phase II/III trial of rosuvastatin with neoadjuvant chemo-radiation in patients with locally advanced rectal cancer
Frontiers in Oncology
rosuvastatin
pathological complete response
neoadjuvant chemoradiation
rectal cancer
drug repurposing
title A randomized phase II/III trial of rosuvastatin with neoadjuvant chemo-radiation in patients with locally advanced rectal cancer
title_full A randomized phase II/III trial of rosuvastatin with neoadjuvant chemo-radiation in patients with locally advanced rectal cancer
title_fullStr A randomized phase II/III trial of rosuvastatin with neoadjuvant chemo-radiation in patients with locally advanced rectal cancer
title_full_unstemmed A randomized phase II/III trial of rosuvastatin with neoadjuvant chemo-radiation in patients with locally advanced rectal cancer
title_short A randomized phase II/III trial of rosuvastatin with neoadjuvant chemo-radiation in patients with locally advanced rectal cancer
title_sort randomized phase ii iii trial of rosuvastatin with neoadjuvant chemo radiation in patients with locally advanced rectal cancer
topic rosuvastatin
pathological complete response
neoadjuvant chemoradiation
rectal cancer
drug repurposing
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1450602/full
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