Relationship of Type II Diabetes and Metformin Use to Ovarian Cancer Progression, Survival, and Chemosensitivity

Abstract

OBJECTIVE-To estimate whether metformin use by ovarian cancer patients with type II diabetes was associated with improved survival. METHODS-We reviewed the effect of diabetes and diabetes medications on ovarian cancer treatment and outcomes in a single-institution retrospective cohort. Inclusion criteria were International Federation of Gynecology and Obstetrics (FIGO) stage I-IV epithelial ovarian, fallopian or peritoneal cancer. Exclusion criteria were noninvasive pathology or non-epithelial malignancies. The primary exposures analyzed were history of type II diabetes and diabetes medications. The primary outcomes were progression-free and overall ovarian cancer survival.RESULTS-Of the 341 ovarian cancer patients included in the study, 297 did not have diabetes, 28 were type II diabetic patients who did not take metformin, and 16 were type II diabetic patients who used metformin. The progression-free survival at five years was 51% for diabetic patients who used metformin compared to 23% for the nondiabetic patients and 8% for the diabetic patients who did not use metformin (P=.03). The overall survival at 5 years was 63%, 37%, and 23% for the diabetic patients who used metformin, the nondiabetic patients, and the diabetic patients who did not use metformin, respectively (P=.03). The patients with diabetes received the same treatment for ovarian cancer as the patients without diabetes. The association of metformin use and increased progression-free survival, but not overall survival, remained significant after controlling for standard clinico-pathologic parameters.CONCLUSION-In this ovarian cancer cohort, the patients with type II diabetes who used metformin had longer progression-free survival, despite receiving similar treatment for ovarian cancer.

Molecular Pathways: Preclinical Models and Clinical Trials with Metformin in Breast Cancer

“…A retrospective case note review of patients with breast cancer receiving neoadjuvant chemotherapy (67) demonstrated a remarkable 24% complete pathologic response (cPR) in diabetic patients incidentally taking metformin and receiving neoadjuvant chemotherapy compared with 16% cPR in nondiabetics and 8% cPR in diabetics not receiving metformin. A similar, also historical, series of epithelial ovarian cancer has demonstrated clinical benefit with increased progression-free survival and overall survival in diabetics taking metformin and receiving taxane/carboplatin chemotherapy compared with nondiabetics or diabetics not on metformin (68). However, incidental metformin use has not demonstrated survival benefit in two case series of diabetics with breast cancer (5,67).…”

Metformin, at Concentrations Corresponding to the Treatment of Diabetes, Potentiates the Cytotoxic Effects of Carboplatin in Cultures of Ovarian Cancer Cells

“…27 However, reports are now starting to show that patients with ovarian cancer with type 2 diabetes who used metformin had longer progression-free survival after surgery and chemotherapy, despite receiving similar treatment. In a single-center study by Romero and colleagues, 27 341 patients with ovarian cancer were evaluated, of which 297 did not have diabetes, 28 had type 2 diabetes and did not use metformin, while 16 type 2 diabetic patients were taking metformin. The authors reported that 5-year progression-free survival for patients undergoing the same chemotherapy treatment was 51% for diabetic patients who used metformin, in comparison to 23% for the nondiabetic patients and 8% for the diabetic patients who did not use metformin.…”

Esophageal Adenocarcinoma: The Influence of Medications Used to Treat Comorbidities on Cancer Prognosis

“…[101][102][103][104][105][106][107][108][109] The inconsistent findings across studies may be due to their retrospective design, inappropriate comparators or the use of exposure data from sources such as medical records and automated pharmacy databases.…”