Evaluation of metformin in early breast cancer: a modification of the traditional paradigm for clinical testing of anti-cancer agents.
Metformin, an inexpensive oral agent commonly used to treat type 2 diabetes, has been garnering increasing attention as a potential anti-cancer agent. Preclinical, epidemiologic, and clinical evidences suggest that metformin may reduce overall cancer risk and mortality, with specific effects in breast cancer. The extensive clinical experience with metformin, coupled with its known (and modest) toxicity, has allowed the traditional process of drug evaluation to be shortened. We review the rationale for a modified approach to evaluation and outline the key steps that will optimize development of this agent in breast cancer, including discussion of a Phase III adjuvant trial (NCIC MA.32) that has recently been initiated.
Goodwin
Pamela J
PJ
Department of Medicine, Division of Clinical Epidemiology at the Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. pgoodwin@mtsinai.on.ca
Stambolic
Vuk
V
Lemieux
Julie
J
Chen
Bingshu E
BE
Parulekar
Wendy R
WR
Gelmon
Karen A
KA
Hershman
Dawn L
DL
Hobday
Timothy J
TJ
Ligibel
Jennifer A
JA
Mayer
Ingrid A
IA
Pritchard
Kathleen I
KI
Whelan
Timothy J
TJ
Rastogi
Priya
P
Shepherd
Lois E
LE
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D011379:Prognosis
D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D008687:Metformin