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Metformin plus lrinotecan in patients with refractory colorectal cancer: a phase 2 clinical trial
BACKGROUND: Patients with refractory colorectal (CRC) cancer have few treatment options. This trial tests the combination of metformin and irinotecan in this setting. METHODS: A phase 2 single-arm trial was conducted, patients received metformin 2500 mg orally a day plus irinotecan 125 mg/m(2) intra...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961008/ https://www.ncbi.nlm.nih.gov/pubmed/33398062 http://dx.doi.org/10.1038/s41416-020-01208-6 |
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author | Bragagnoli, Arinilda Campos Araujo, Raphael L. C. Ferraz, Mauricio Wagner dos Santos, Lucas Vieira Abdalla, Kathia Cristina Comar, Fabiana Santos, Florinda Almeida Oliveira, Marco Antonio Carvalheira, José Barreto Campello Cárcano, Flávio Mavigner da Silveira Nogueira Lima, João Paulo |
author_facet | Bragagnoli, Arinilda Campos Araujo, Raphael L. C. Ferraz, Mauricio Wagner dos Santos, Lucas Vieira Abdalla, Kathia Cristina Comar, Fabiana Santos, Florinda Almeida Oliveira, Marco Antonio Carvalheira, José Barreto Campello Cárcano, Flávio Mavigner da Silveira Nogueira Lima, João Paulo |
author_sort | Bragagnoli, Arinilda Campos |
collection | PubMed |
description | BACKGROUND: Patients with refractory colorectal (CRC) cancer have few treatment options. This trial tests the combination of metformin and irinotecan in this setting. METHODS: A phase 2 single-arm trial was conducted, patients received metformin 2500 mg orally a day plus irinotecan 125 mg/m(2) intravenously weekly D1 and D8 every 21 days. The primary endpoint was the disease control rate according to the Response Evaluation Criteria in Solid Tumors version 1.1 at 12 weeks. RESULTS: Between December 2015 and January 2018, 41 patients were enrolled. Seventeen patients (41%) met the primary endpoint of disease control in 12 weeks; hence, the study was deemed positive. The median progression-free survival was 3.3 months (CI 95%, 2.0–4.5 months), and the median overall survival was 8.4 months (CI 95%, 5.9–10.8 months). Both mutation RAS status and disease control at 12 weeks impacted overall survival in the multivariate model (HR 2.28, CI 95%, 1.12–4.7, p = 0.02; and HR 0.21, CI 95%, 0.08–0.5, p = 0.001, respectively). The most common adverse event was diarrhoea (29.2% grade 3). CONCLUSIONS: In this trial, metformin plus irinotecan demonstrated disease control in patients with refractory CRC. Further trials with optimised diarrhoea control are needed to confirm these results. |
format | Online Article Text |
id | pubmed-7961008 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79610082022-01-04 Metformin plus lrinotecan in patients with refractory colorectal cancer: a phase 2 clinical trial Bragagnoli, Arinilda Campos Araujo, Raphael L. C. Ferraz, Mauricio Wagner dos Santos, Lucas Vieira Abdalla, Kathia Cristina Comar, Fabiana Santos, Florinda Almeida Oliveira, Marco Antonio Carvalheira, José Barreto Campello Cárcano, Flávio Mavigner da Silveira Nogueira Lima, João Paulo Br J Cancer Article BACKGROUND: Patients with refractory colorectal (CRC) cancer have few treatment options. This trial tests the combination of metformin and irinotecan in this setting. METHODS: A phase 2 single-arm trial was conducted, patients received metformin 2500 mg orally a day plus irinotecan 125 mg/m(2) intravenously weekly D1 and D8 every 21 days. The primary endpoint was the disease control rate according to the Response Evaluation Criteria in Solid Tumors version 1.1 at 12 weeks. RESULTS: Between December 2015 and January 2018, 41 patients were enrolled. Seventeen patients (41%) met the primary endpoint of disease control in 12 weeks; hence, the study was deemed positive. The median progression-free survival was 3.3 months (CI 95%, 2.0–4.5 months), and the median overall survival was 8.4 months (CI 95%, 5.9–10.8 months). Both mutation RAS status and disease control at 12 weeks impacted overall survival in the multivariate model (HR 2.28, CI 95%, 1.12–4.7, p = 0.02; and HR 0.21, CI 95%, 0.08–0.5, p = 0.001, respectively). The most common adverse event was diarrhoea (29.2% grade 3). CONCLUSIONS: In this trial, metformin plus irinotecan demonstrated disease control in patients with refractory CRC. Further trials with optimised diarrhoea control are needed to confirm these results. Nature Publishing Group UK 2021-01-04 2021-03-16 /pmc/articles/PMC7961008/ /pubmed/33398062 http://dx.doi.org/10.1038/s41416-020-01208-6 Text en © The Author(s), under exclusive licence to Cancer Research UK 2021 https://creativecommons.org/licenses/by/4.0/ Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0). |
spellingShingle | Article Bragagnoli, Arinilda Campos Araujo, Raphael L. C. Ferraz, Mauricio Wagner dos Santos, Lucas Vieira Abdalla, Kathia Cristina Comar, Fabiana Santos, Florinda Almeida Oliveira, Marco Antonio Carvalheira, José Barreto Campello Cárcano, Flávio Mavigner da Silveira Nogueira Lima, João Paulo Metformin plus lrinotecan in patients with refractory colorectal cancer: a phase 2 clinical trial |
title | Metformin plus lrinotecan in patients with refractory colorectal cancer: a phase 2 clinical trial |
title_full | Metformin plus lrinotecan in patients with refractory colorectal cancer: a phase 2 clinical trial |
title_fullStr | Metformin plus lrinotecan in patients with refractory colorectal cancer: a phase 2 clinical trial |
title_full_unstemmed | Metformin plus lrinotecan in patients with refractory colorectal cancer: a phase 2 clinical trial |
title_short | Metformin plus lrinotecan in patients with refractory colorectal cancer: a phase 2 clinical trial |
title_sort | metformin plus lrinotecan in patients with refractory colorectal cancer: a phase 2 clinical trial |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961008/ https://www.ncbi.nlm.nih.gov/pubmed/33398062 http://dx.doi.org/10.1038/s41416-020-01208-6 |
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