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Lee, Kim, Lee, Park, Hong, Cheon, Kim, and Kim: The Effect of Metformin on Responses to Chemotherapy and Survival in Stage IV Colorectal Cancer with Diabetes
Original Article
Alimentary Tract
The Korean Journal of Gastroenterology

The Korean Journal of Gastroenterology 2012; 60(6): 355-361.

Published online: 17 December 2012

DOI: https://doi.org/10.4166/kjg.2012.60.6.355

The Effect of Metformin on Responses to Chemotherapy and Survival in Stage IV Colorectal Cancer with Diabetes

Dong-Jun Lee, Bun Kim, Jin Ha Lee, Su Jung Park, Sung Pil Hong, Jae Hee Cheon, Tae Il Kim, Won Ho Kim

Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.

Correspondence to: Tae Il Kim, Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea. Tel: +82-2-2228-1965, Fax: +82-2-393-6884, taeilkim@yuhs.ac

Received 4 July 2012       Revised 22 August 2012       Accepted 24 August 2012

Copyright © 2012 The Korean Society of Gastroenterology

(open-access):

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims

Metformin is known to lower the risk of cancer and cancer mortality. However, the effect of metformin in stage IV colorectal cancer (CRC) patients with diabetes mellitus (DM) remains unknown. The aim of this study was to evaluate the effect of metformin on tumor response and survival in stage IV CRC patients with DM.

Methods

We identified 106 patients who were diagnosed with both stage IV CRC and DM (81 patients who underwent palliative chemotherapy and 25 patients who underwent curative resection). Retrospective data of each patient's clinical characteristics, tumor response, and survival rate were compared between two groups of patients who either were or were not administered metformin.

Results

For the palliative chemotherapy group, tumor response, change in target lesion size, progression free survival rate, and overall survival rate were not significantly different between the metformin group and the non-metformin group on univariate and multivariate analysis. For the curative resection patient group, metformin use was associated with increased disease free survival on univariate analysis (p=0.012) and multivariate analysis (hazard ratio, 0.024; 95% CI 0.001-0.435; p=0.010), but not with overall survival.

Conclusions

Metformin use in stage IV CRC patients with diabetes was shown to be associated with a lower risk of tumor recurrence after curative resection.

Keywords: Colorectal neoplasms, Diabetes mellitus, Metformin, Recurrence

Figures and Tables

Fig. 1
Comparison of progression free survival (A) and overall survival (B) in stage IV colorectal cancer patients with diabetes mellitus who underwent palliative chemotherapy.
kjg-60-355-g001
Fig. 2
Comparison of disease free survival according to metformin use in 25 stage IV colorectal cancer (CRC) patients with diabetes mellitus (DM) who underwent curative resection without preoperative chemotherapy (A) and 37 stage IV CRC patients with DM who underwent curative resection with or without preoperative chemotherapy (B).
kjg-60-355-g002
Table 1
Baseline Characteristics of 81 Patients with Stage IV Colorectal Cancer and Diabetes Mellitus Who Underwent Palliative Chemotherapy
kjg-60-355-i001

Values are presented as mean±SD or number (%).

Targeted agents include bevasizumab and cetuximab.

ECOG, Eastern Cooperative Oncology Group; HbA1c, hemoglobin A1c; 5-FU, 5-fluorouracil; FOLFOX, 5-fluorouracil-leucovorin-oxaliplatin; FOLFIRI, 5-fluorouracil-leucovorin-irinotecan.

Table 2
Baseline Characteristics of 25 Patients with Stage IV Colorectal Cancer and Diabetes Mellitus Who Underwent Curative Resection
kjg-60-355-i002

Values are presented as mean±SD or number (%).

Targeted agents include bevasizumab and cetuximab.

ECOG, Eastern Cooperative Oncology Group; HbA1c, hemoglobin A1c; 5-FU, 5-fluorouracil; FOLFOX, 5-fluorouracil-leucovorin-oxaliplatin; FOLFIRI, 5-fluorouracil-leucovorin-irinotecan.

Table 3
Comparison of 1st Response Evaluation according to Metformin Use in Stage IV Colorectal Cancer Patients with Diabetes Mellitus Who Underwent Palliative Chemotherapy
kjg-60-355-i003

Values are presented as mean±SD or number of patients (%).

aChange in the sum of the longest diameters of all target lesions (%).

Table 4
Univariate and Multivariate Adjusted Progression Free Survival and Overall Survival according to Metformin Use in Stage IV Colorectal Cancer Patients with Diabetes Mellitus Who Underwent Palliative Chemotherapy
kjg-60-355-i004

aAdjusted variables: age, sex, BMI, lab (WBC, cholesterol, sugar, hemoglobin A1c), diabetes mellitus duration, smoking, comorbidity, aspirin use.

Table 5
Univariate and Multivariate Adjusted Disease Free Survival and Overall Survival according to Metformin Use in Stage IV Colorectal Cancer Patients with Diabetes Mellitus Who Underwent Curative Resection without Preoperative Chemotherapy
kjg-60-355-i005

aAdjusted variables: age, sex, BMI, lab (WBC, cholesterol, sugar, hemoglobin A1c), diabetes mellitus duration, smoking, comorbidity, aspirin use.

bAdjusted variables: age, sex, BMI.

Table 6
Univariate and Multivariate Adjusted Disease Free Survival and Overall Survival according to Metformin Use in Stage IV Colorectal Cancer Patients with Diabetes Mellitus Who Underwent Curative Resection with or without Preoperative Chemotherapy
kjg-60-355-i006

aAdjusted variables: age, sex, BMI, lab (WBC, cholesterol, sugar, hemoglobin A1c), diabetes mellitus duration, smoking, comorbidity, aspirin use.

bAdjusted variables: age, sex, BMI.

Notes

Financial support: None.

Conflict of interest: None.

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