TY - JOUR
T1 - Relationship between metformin use and recurrence and survival in patients with resected stage III colon cancer receiving adjuvant chemotherapy
T2 - Results from north central cancer treatment group N0147 (Alliance)
AU - Singh, Preet Paul
AU - Shi, Qian
AU - Foster, Nathan R.
AU - Grothey, Axel
AU - Nair, Suresh G.
AU - Chan, Emily
AU - Shields, Anthony F.
AU - Goldberg, Richard M.
AU - Gill, Sharlene
AU - Kahlenberg, Morton S.
AU - Sinicrope, Frank A.
AU - Sargent, Daniel J.
AU - Alberts, Steven R.
N1 - Funding Information:
We acknowledge the accrual of patients by Balkrishna Jahagirdar, Metro-Minnesota National Cancer Institute Community Oncology Research Program, supported by Grant UG1CA189863. This work was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821 (to the Alliance for Clinical Trials in Oncology) and U10CA82 (Alliance Statistics and Data Center), P30CA016058, U10CA025224, U10CA076001, U10CA180820, U10CA180833, U10CA180835, U10CA180847, U10CA180850, and U10CA180888. Support was also received romthe Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota (to P.P.S. and S.R.A.). Support for correlative studies was also provided by unrestricted funds from Bristol-Myers Squibb, ImClone, Sanofi-Aventis, and Pfizer. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Previously presented at the 2015 American Society of Clinical Oncology Annual Conference, Chicago, IL.
Publisher Copyright:
© AlphaMed Press 2016.
PY - 2016/12
Y1 - 2016/12
N2 - Background. Preclinical and epidemiological data suggest that metformin might have antineoplastic properties against colon cancer (CC). However, the effect of metformin use on patient survival in stage III CC after curative resection is unknown. The survival outcomes were comparable regardless of the duration of metformin use. PATIENTS AND METHODS: Before randomization to FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) with or without cetuximab, 1,958 patients with stage III CC enrolled in the N0147 study completed a questionnaire with information on diabetes mellitus (DM) and metformin use. Cox models were used to assess the association between metformin use and disease-free survival (DFS), overall survival (OS), and the time to recurrence (TTR), adjusting for clinical and/or pathological factors. RESULTS: Of the 1,958 patients, 1,691 (86%) reported no history of DM, 115 reported DM with metformin use (6%), and 152 reported DM without metformin use (8%). The adjuvant treatment arms were pooled, because metformin use showed homogeneous effects on outcomes across the two arms. Among the patients with DM (n = 267), DFS (adjusted hazard ratio [aHR], 0.90; 95% confidence interval [CI], 0.59-1.35; p = .60), OS (aHR, 0.99; 95% CI, 0.65-1.49; p = .95), and TTR (aHR, 0.87; 95% CI, 0.56-1.35; p = .53) were not different for the metformin users compared with the nonusers after adjusting for tumor and patient factors. The survival outcomes were comparable regardless of the duration of metformin use (<1, 1-5, 6-10, ≥11 years) before randomization (ptrend = .64 for DFS, ptrend = .84 for OS, and ptrend = .87 for TTR). No interaction effects were observed between metformin use and KRAS, BRAF mutation status, tumor site, T/N stage, gender, or age. CONCLUSIONS: Patients with stage III CC undergoing adjuvant chemotherapy who used metformin before the diagnosis of CC experienced DFS, OS, and TTR similar to those for non-DM patients and DM patients without metformin use.
AB - Background. Preclinical and epidemiological data suggest that metformin might have antineoplastic properties against colon cancer (CC). However, the effect of metformin use on patient survival in stage III CC after curative resection is unknown. The survival outcomes were comparable regardless of the duration of metformin use. PATIENTS AND METHODS: Before randomization to FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) with or without cetuximab, 1,958 patients with stage III CC enrolled in the N0147 study completed a questionnaire with information on diabetes mellitus (DM) and metformin use. Cox models were used to assess the association between metformin use and disease-free survival (DFS), overall survival (OS), and the time to recurrence (TTR), adjusting for clinical and/or pathological factors. RESULTS: Of the 1,958 patients, 1,691 (86%) reported no history of DM, 115 reported DM with metformin use (6%), and 152 reported DM without metformin use (8%). The adjuvant treatment arms were pooled, because metformin use showed homogeneous effects on outcomes across the two arms. Among the patients with DM (n = 267), DFS (adjusted hazard ratio [aHR], 0.90; 95% confidence interval [CI], 0.59-1.35; p = .60), OS (aHR, 0.99; 95% CI, 0.65-1.49; p = .95), and TTR (aHR, 0.87; 95% CI, 0.56-1.35; p = .53) were not different for the metformin users compared with the nonusers after adjusting for tumor and patient factors. The survival outcomes were comparable regardless of the duration of metformin use (<1, 1-5, 6-10, ≥11 years) before randomization (ptrend = .64 for DFS, ptrend = .84 for OS, and ptrend = .87 for TTR). No interaction effects were observed between metformin use and KRAS, BRAF mutation status, tumor site, T/N stage, gender, or age. CONCLUSIONS: Patients with stage III CC undergoing adjuvant chemotherapy who used metformin before the diagnosis of CC experienced DFS, OS, and TTR similar to those for non-DM patients and DM patients without metformin use.
KW - Adjuvant chemotherapy
KW - Colon cancer
KW - Diabetes mellitus
KW - Metformin
KW - Recurrence
KW - Survival
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U2 - 10.1634/theoncologist.2016-0153
DO - 10.1634/theoncologist.2016-0153
M3 - Article
C2 - 27881709
AN - SCOPUS:85006823153
SN - 1083-7159
VL - 21
SP - 1509
EP - 1512
JO - Oncologist
JF - Oncologist
IS - 12
ER -