A phase II randomized clinical trial of the effect of metformin versus placebo on progression-free survival in women with metastatic breast cancer receiving standard chemotherapy.

Autor: Pimentel I; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada. Electronic address: immpsp@gmail.com., Lohmann AE; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada., Ennis M; Applied Statistician, 9227, Kennedy Road, Markham; Ontario, Canada., Dowling RJO; Princess Margaret Cancer Centre, University Health Network, Ontario, Canada., Cescon D; Princess Margaret Cancer Centre, University Health Network, Ontario, Canada., Elser C; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada; Princess Margaret Cancer Centre, University Health Network, Ontario, Canada., Potvin KR; Western University, London, ON, Canada., Haq R; St. Michael's Hospital, University of Toronto, Toronto, ON, Canada., Hamm C; Western University, London, ON, Canada., Chang MC; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, VT, USA., Stambolic V; Princess Margaret Cancer Centre, University Health Network, Ontario, Canada., Goodwin PJ; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Jazyk: angličtina
Zdroj: Breast (Edinburgh, Scotland) [Breast] 2019 Dec; Vol. 48, pp. 17-23. Date of Electronic Publication: 2019 Aug 22.
DOI: 10.1016/j.breast.2019.08.003
Abstrakt: Objectives: Pre-clinical data suggest metformin might enhance the effect of chemotherapy in breast cancer (BC). We conducted a Phase II randomized trial of chemotherapy plus metformin versus placebo in metastatic breast cancer (MBC).
Material and Methods: In this double blind phase II trial we randomly assigned non-diabetic MBC patients on 1st to 4th line chemotherapy to receive metformin 850 mg po bid or placebo bid. Primary outcome was progression-free survival (PFS); secondary outcomes included overall survival (OS), response rate (RR), toxicity and quality of life (QOL). With 40 subjects and a type-one error of 0.2 (one-sided), a PFS hazard ratio (HR) of 0.58 could be detected with 80% power.
Results: 40 patients were randomized (22 metformin, 18 placebo) with a mean age of 55 vs 57 years and ER/PR positive BC in 86.4% vs 83.3% off metformin vs placebo, respectively. Mean BMI was 27kg/m2 in both arms. The majority of patients were on 1st line chemotherapy. Grade 3-4 toxicity occurred in 31.8% (metformin) vs 58.8% (placebo). Best response: Partial response 18.2% metformin vs 25% placebo, stable disease 36.4% metformin vs 18.8% placebo, progressive disease 45.4% metformin vs 56.2% placebo. Mean PFS was 5.4 vs 6.3 months (metformin vs placebo), HR 1.2 (95% CI 0.63-2.31). Mean OS was 20.2 (metformin) vs 24.2 months (placebo), HR 1.68 (95% CI 0.79-3.55).
Conclusion: In this population metformin showed no significant effect on RR, PFS or OS. These results do not support the use of metformin with chemotherapy in non-diabetic MBC patients.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: