Metformin plus lrinotecan in patients with refractory colorectal cancer: a phase 2 clinical trial

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 intraven...

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Bibliographic Details
Published in:British journal of cancer Vol. 124; no. 6; pp. 1072 - 1078
Main Authors: 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
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 16-03-2021
Nature Publishing Group
Subjects:
631/67/1059/153
692/4028/67/1059/99
Adult
Aged
Antidiabetics
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biomedical and Life Sciences
Biomedicine
Cancer Research
Clinical trials
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - pathology
Diarrhea
Disease control
Drug Resistance
Epidemiology
Female
Follow-Up Studies
Humans
Irinotecan
Irinotecan - administration & dosage
Male
Metformin
Metformin - administration & dosage
Middle Aged
Molecular Medicine
Neoplasm Recurrence, Local - drug therapy
Neoplasm Recurrence, Local - pathology
Oncology
Patients
Prognosis
Solid tumors
Survival
Survival Rate
Young Adult
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Summary: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.
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ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-020-01208-6