Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Mar 19:15:1450602.
doi: 10.3389/fonc.2025.1450602. eCollection 2025.

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

Prachi S Patil  1 , Avanish Saklani  2 , Naveena A N Kumar  3 , Ashwin De'Souza  2 , Rahul Krishnatry  4 , Snehal Khanvilkar  5 , Mufaddal Kazi  2 , Reena Engineer  4 , Vikas Ostwal  6 , Anant Ramaswamy  6 , Munita Bal  7 , Priya Ranganathan  8 , Ekta Gupta  9   10 , Sanjeev Galande  9   10
Affiliations

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

Prachi S Patil et al. Front Oncol. .

Abstract

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.

Keywords: drug repurposing; neoadjuvant chemoradiation; pathological complete response; rectal cancer; rosuvastatin.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow chart depicting the molecular sub-study.
Figure 2
Figure 2
CONSORT flow diagram depicting the trial schema for treatment decisions. .
See this image and copyright information in PMC

References

    1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. (2015) 65:87–108. doi: 10.3322/caac.21262 - DOI - PubMed
    1. Fact Sheets by Population – CRC India ASRs . Available online at: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx (Accessed May 10, 2024).
    1. Sirohi B, Shrikhande SV, Perakath B, Raghunandharao D, Julka PK, Lele V, et al. . Indian Council of Medical Research consensus document for the management of colorectal cancer. Indian J Med Paediatr Oncol. (2014) 35(03):192–6. - PMC - PubMed
    1. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. . Pre-operative vs. post- operative chemo- radiotherapy for rectal cancer. N Engl J Med. (2004) 351:1731–40. doi: 10.1056/NEJMoa040694 - DOI - PubMed
    1. van der Paardt MP, Zagers MB, Beets-Tan RG, Stoker J, Bipat S. Patients who undergo pre-operative chemoradiotherapy for locally advanced rectal cancer re-staged by using diagnostic MR imaging: a systematic review and meta-analysis. Radiology. (2013) 269:101–12. doi: 10.1148/radiol.13122833 - DOI - PubMed

LinkOut - more resources