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Ann Oncol. 2016 Feb;27(2):262-6. doi: 10.1093/annonc/mdv539. Epub 2015 Nov 16.

Phase II study of medroxyprogesterone acetate plus metformin as a fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer.

Author information

1
Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Chiba antira@faculty.chiba-u.jp.
2
Clinical Research Center, Chiba University Hospital, Chiba.
3
Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan.
4
Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Chiba.

Abstract

BACKGROUND:

Metformin, widely used in the treatment of type 2 diabetes mellitus, reduces the risk of cancer and relapse after treatment. Fertility-sparing treatment for endometrial cancer (EC) with progestin is associated with a high chance of disease regression, and the high relapse rate continues to be a problem. We assessed the efficacy of metformin in preventing recurrence after medroxyprogesterone acetate (MPA) as fertility-sparing treatment for atypical endometrial hyperplasia (AEH) and EC.

PATIENTS AND METHODS:

This phase II study enrolled 17 patients with AEH and 19 patients with EC limited to the endometrium (age, 20-40 years). MPA (400 mg/day) and metformin (750-2250 mg/day) were administered for 24-36 weeks to achieve a complete response (CR). Metformin was administered until conception, even after MPA discontinuation. The primary end point was relapse-free survival (RFS) after remission. We analyzed all efficacy end points in the full analysis set.

RESULTS:

The body mass index was ≥25 kg/m(2) in 27 patients (mean, 31 kg/m(2); range, 19-51 kg/m(2)), and the homeostasis model assessment for insulin resistance index was ≥2.5 in 24 patients (mean, 4.7; range, 0.7-21). Two patients showed progression at 12 weeks [6%; 95% confidence interval (CI) 2-18]. At 36 weeks, 29 (81%; 95% CI 65-90) patients achieved CR, and 5 (14%; 95% CI 6-29) patients achieved partial response. During a median follow-up of 38 months (range, 9-66 months) after remission, relapse was confirmed in three of the patients who had achieved CR (relapse rate, 10%). The 3-year estimated RFS rate was 89%. No patients experienced severe toxicity.

CONCLUSIONS:

Metformin inhibited disease relapse after MPA therapy. The combination of metformin and MPA in EC treatment should be studied further.

TRIAL REGISTRATION NUMBER:

UMIN 000002210.

KEYWORDS:

endometrial cancer; fertility-sparing treatment; insulin resistance; medroxyprogesterone acetate; metformin

PMID:
26578736
DOI:
10.1093/annonc/mdv539
[Indexed for MEDLINE]

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