Metformin intervention against ovarian toxicity during chemotherapy for early breast cancer: Study protocol for a randomized double-blind placebo-controlled trial

Maturitas. 2020 Jul:137:1-6. doi: 10.1016/j.maturitas.2020.04.010. Epub 2020 Apr 21.

Abstract

Background: With the significant improvement of the cure rate and survival rate of cancer patients, the survivors face quality-of-life problems, such as a significant decline in reproductive system development, ovarian reserves and function, and even fertility loss and early menopause. These problems are often highly associated with chemotherapy-induced ovarian damage in cancer treatment. However, there are no ideal treatment strategies at present. In our attempt to develop reagents and approaches for delaying ovarian aging and protecting chemotherapy-induced ovarian injury, we recently found that metformin may be the most promising drug to protect female malignant tumor patients from chemotherapy-induced ovarian injury. This trial aims to test whether administration of metformin during chemotherapy can protect the normal ovarian function of patients with early breast cancer.

Methods: This study is prospective, randomized, double-blind and placebo-controlled. Female patients with early breast cancer (N = 314) will be randomly assigned to two groups (placebo, metformin 2000 mg). Metformin will be administered during and after chemotherapy for patients with stage I-IIIa breast cancer. The primary outcome will be the menstruation recovery rate 12 months after chemotherapy, defined as recovery of menstruation twice in a row within 1 year. Patients will be followed up for 5 years to observe long-term ovarian function and prognosis, such as overall survival (OS), objective response rate (ORR), and disease-free survival (DFS). Quality of life and safety will also be assessed.

Discussion: Our research will provide a new treatment strategy for fertility protection, and clinical treatment guidance for cancer patients.

Keywords: Breast cancer; Chemotherapy; Metformin; Ovarian toxicity.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Double-Blind Method
  • Female
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Menstruation / drug effects*
  • Metformin / pharmacology
  • Metformin / therapeutic use*
  • Middle Aged
  • Ovarian Function Tests
  • Ovary / drug effects*
  • Ovary / pathology
  • Ovary / physiopathology
  • Prospective Studies
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • Recovery of Function / drug effects
  • Survival Rate
  • Young Adult

Substances

  • Hypoglycemic Agents
  • Metformin