Ovarian Cancer Findings Support Metformin

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Ovarian cancer findings support metformin's antitumor effects
Last Updated: 2012-01-06 10:22:27 -0400 (Reuters Health)
By Megan Brooks
NEW YORK (Reuters Health) - In a review of ovarian cancer outcomes, women with diabetes
survived longer if they took metformin -- and on progression-free survival the diabetics who used
metformin did better even compared to women who didn't have diabetes at all.
Dr. Iris L. Romero and colleagues from the University of Chicago, Illinois say their observations add
to a "growing body of evidence" from epidemiologic and preclinical studies indicating that metformin
has antitumor effects.
"There is also a biologically plausible mechanism mediating metformin's protective effect in cancer
through AMPK (adenosine monophosphate-activated protein kinase) activation and inhibition of insulin
signaling," Dr. Romero noted in an email to Reuters Health.
The study team looked at data on 341 women with stage I to IV epithelial ovarian (n = 273),
fallopian (n = 34), or peritoneal (n = 34) cancer treated at their institution between 1992 and 2010.
The cohort included 16 diabetics who used metformin and another 28 who did not.
Women received same treatment for ovarian cancer regardless of whether they had diabetes. Rates
of primary cytoreductive surgery with residual disease smaller than 1 cm after surgery, the type of
chemotherapy used, and the average number of chemotherapy cycles were similar among the
groups. Nearly all of the women (95%) received both platinum-based and taxane-based
chemotherapy, most commonly carboplatin and taxol.
But as the study team reports this month in Obstetrics and Gynecology, five-year progression-free
survival rates were 51% in diabetic patients who used metformin, 8% in diabetic patients who did
not use metformin, and 23% in nondiabetics (p=0.03).
Overall survival at five years was 63% in metformin users, 23% in non-metformin users and 37%
in the nondiabetic group (p=0.03).
After controlling for "standard clinicopathologic parameters," metformin use remained significantly
associated with progression-free survival, but not with overall survival, the investigators said.
In a survival analysis adjusted for confounding factors, comparing diabetic metformin users to
diabetic nonusers, the risk of disease recurrence was significantly decreased in metformin users
(hazard ratio 0.38). The metformin group also had a lower risk of dying during the study (hazard
ratio 0.43), although this difference failed to reach statistical significance.
The risk of disease recurrence and death were also lower in patients with diabetes who used
metformin when compared with the nondiabetic group, but this reduction was not statistically
significant.
In contrast, patients with diabetes who did not take metformin were more apt to have their cancer
recur (hazard ratio, 1.42) and to die of their disease (hazard ratio, 1.33) when compared with
patients without diabetes.
These findings, note the researchers, are in line with other studies that have demonstrated
anticancer effects of metformin in several cancers including breast, prostate, colon and ovarian
cancer.
Clinical and laboratory studies have also suggested that metformin may improve response to
chemotherapy. In the current study, the best response to chemotherapy occurred in metformin users,
Dr. Romero and colleagues say.
Given the retrospective nature of the study, the results should be considered hypothesis-generating
and should not be generalized to clinical practice, the authors emphasize.
Also, they say, the small sample size limited their ability to find a difference in survival between
diabetic metformin users and nondiabetic patients and kept them from analyzing the effects of
diabetic medications other than metformin. Furthermore, the researchers could not control for
diabetes severity.
Despite these limitations, the researchers say the idea that specific anti-diabetes treatments affect
cancer survival is clinically relevant given the increasing prevalence of diabetes.
The World Health Organization estimates that 171 million people worldwide have type 2 diabetes, a
number that is expected to double by 2030.
"If future studies continue to support the protective effect of metformin in cancer, then this will be
an important consideration when managing diabetic patients with cancer," Dr. Romero and colleagues
conclude.
"It is also important to note that metformin has a strong track record of safety, is inexpensive and
is already widely used," Dr. Romero told Reuters Health.
She added that prospective randomized clinical trials are needed looking at metformin as
chemoprevention for patients at high-risk of developing ovarian cancer and as adjuvant treatment
and maintenance during and after chemotherapy. Such trials are already under way in breast
cancer, she said.
The study was supported by grants from the National Institutes of Health and the Gynecologic
Cancer Foundation/St. Louis Ovarian Cancer Awareness. The authors have disclosed no relevant
conflicts of interest.
SOURCE: http://bit.ly/A9smFS
Obstet Gynecol 2012;119:61-67. SOURCE: http://bit.ly/A9smFS Obstet Gynecol 2012;119:61-67.
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