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Tytuł:
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(Ir)relevance of Metformin Treatment in Patients with Metastatic Pancreatic Cancer: An Open-Label, Randomized Phase II Trial.
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Autorzy:
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Reni M; Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. .
Dugnani E; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Cereda S; Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Belli C; Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Balzano G; Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Nicoletti R; Department of Radiology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Liberati D; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Pasquale V; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Scavini M; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Maggiora P; Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Sordi V; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Lampasona V; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Ceraulo D; Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Di Terlizzi G; Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Doglioni C; Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy. Vita-Salute San Raffaele University, Milan, Italy.
Falconi M; Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. Vita-Salute San Raffaele University, Milan, Italy.
Piemonti L; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy. .
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Źródło:
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Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2016 Mar 01; Vol. 22 (5), pp. 1076-85. Date of Electronic Publication: 2015 Oct 12.
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Typ publikacji:
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Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: Denville, NJ : The Association, c1995-
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MeSH Terms:
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Antineoplastic Combined Chemotherapy Protocols/*administration & dosage
Metformin/*administration & dosage
Pancreatic Neoplasms/*drug therapy
Adult ; Aged ; Capecitabine/administration & dosage ; Cisplatin/administration & dosage ; Deoxycytidine/administration & dosage ; Deoxycytidine/analogs & derivatives ; Disease-Free Survival ; Epirubicin/administration & dosage ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Pancreatic Neoplasms/pathology ; Treatment Outcome ; Gemcitabine
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Substance Nomenclature:
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0W860991D6 (Deoxycytidine)
3Z8479ZZ5X (Epirubicin)
6804DJ8Z9U (Capecitabine)
9100L32L2N (Metformin)
Q20Q21Q62J (Cisplatin)
0 (Gemcitabine)
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Entry Date(s):
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Date Created: 20151014 Date Completed: 20161213 Latest Revision: 20221207
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Update Code:
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20240104
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DOI:
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10.1158/1078-0432.CCR-15-1722
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PMID:
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26459175
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Purpose: We aimed to assess the safety and efficacy of metformin for treating patients with metastatic pancreatic cancer and to identify endocrine and metabolic phenotypic features or tumor molecular markers associated with sensitivity to metformin antineoplastic action.
Experimental Design: We designed an open-label, randomized, phase II trial to assess the efficacy of adding metformin to a standard systemic therapy with cisplatin, epirubicin, capecitabine, and gemcitabine (PEXG) in patients with metastatic pancreatic cancer. Patients ages 18 years or older with metastatic pancreatic cancer were randomly assigned (1:1) to receive PEXG every 4 weeks in combination or not with 2 g oral metformin daily. The primary endpoint was 6-months progression-free survival (PFS-6) in the intention-to-treat population.
Results: Between August 2010 and January 2014, we randomly assigned 60 patients to receive PEXG with (n = 31) or without metformin (n = 29). At the preplanned interim analysis, the study was ended for futility. PFS-6 was 52% [95% confidence interval (CI), 33-69] in the control group and 42% (95% CI, 24-59) in the metformin group (P = 0.61). Furthermore, there was no difference in disease-free survival and overall survival between groups. Despite endocrine metabolic modifications induced by metformin, there was no correlation with the outcome. Single-nucleotide polymorphism rs11212617 predicted glycemic response, but not tumor response to metformin. Gene expression on tumor tissue did not predict tumor response to metformin.
Conclusions: Addition of metformin at the dose commonly used in diabetes did not improve outcome in patients with metastatic pancreatic cancer treated with standard systemic therapy. See related commentary by Yang and Rustgi, p. 1031.
(©2015 American Association for Cancer Research.)
Comment in: Clin Cancer Res. 2016 Mar 1;22(5):1031-3. (PMID: 26637275)
