Phase 2 trial tests metformin with neoadjuvant radiochemotherapy for locally advanced rectal cancer

This Phase 2 trial (METCAP) investigated the efficacy of adding metformin to standard neoadjuvant radiochemotherapy for the treatment of locally advanced rectal cancer. The study enrolled 60 patients. The intervention involved a metformin regimen starting at 850 mg twice daily (1700 mg/day) 48 hours after a baseline dosimetric scan. After a minimum of 7 days, and up to 48 hours before surgery, the dosage was increased to 850 mg three times daily (2550 mg/day). On the same day as the dosage increase (J10), patients began a 5-week course of radiochemotherapy. This consisted of capecitabine at 800 mg/m² twice daily (1600 mg/m²/day) alongside 3D irradiation or Intensity-Modulated Radiation Therapy (IMRT) delivering a total dose of 50 Gy (5 sessions of 2 Gy per week). Surgery was scheduled for 6 to 8 weeks after completing chemoradiotherapy. The primary efficacy endpoint was the complete histological response rate (pathological complete response, pCR), defined as the absence of tumor cells in the operative specimen. The study was completed, with enrollment from May 2015 to March 2017. The abstract provides the rationale based on historical cohort data suggesting improved survival in diabetic patients on metformin and in vitro studies demonstrating anti-proliferative properties, but does not report the specific pCR results, safety data, or other secondary outcomes from the trial.

When you're facing a diagnosis of locally advanced rectal cancer, the treatment path is intense: weeks of chemotherapy and radiation to shrink the tumor before surgery. This study asked a simple but important question: could adding a common, well-known diabetes pill make that pre-surgery treatment work better? The drug is called metformin. Doctors had noticed that people with diabetes who took metformin seemed to have better survival odds, and lab studies showed the drug could slow cancer cell growth. So, they designed a trial to test it in people with this specific cancer. In the study, patients took metformin pills alongside their standard pre-surgery chemo and radiation. The goal was to see if this combination led to what doctors call a 'complete pathological response'—meaning when the surgeon removed the tissue, no cancer cells could be found under the microscope. Finding no cancer cells after this intense treatment is a very good sign. The study enrolled 60 people to see if this accessible, repurposed drug could offer them a better chance.