Neoadjuvant Metformin in Association to Chemoradiotherapy for Locally Advanced Rectal Cancer

Inclusion Criteria: * 18 years or older; * biopsy proven poorly differentiated carcinoma or adenocarcinoma of the rectum; * lesions located within 12 cm of the anal verge (from colonoscopy assessment); * ability to tolerate oral treatment; * locally advanced tumor, classified by the presence of positive regional lymph nodes or primary tumor invasion beyond the serosa (T3 or T4), assessed by MRI; * eligibility for curative surgery (no distant metastasis or invasion of bony structures of the pelvis); * Performance Status (PS) Eastern Cooperative Oncology Group (ECOG) 0-2; * adequate hematologic functions (hemoglobin ≥ 10 g / dL \[5.6 mmol / L\]; neutrophil count ≥ 1,500 / mm3 and platelet count ≥ 100,000 / mm3), adequate renal function (serum creatinine less than 1.5 times the UNL) and adequate hepatic function (bilirubin less than 1.5 times the UNL; aspartate aminotransferase and alanine aminotransferase less than 2.5 times the UNL); Exclusion Criteria: * known hypersensitivity to metformin or its excipients; * squamous carcinomas of the rectum or anal canal; * chronic treatment with corticosteroids or other immunosuppressive agents; * treatment with oral antidiabetic products; * distant metastasis at diagnosis or tumor invasion of pelvic bone structures that may proscribe curative intent surgery; * chronic or acute infections; * use of drugs under study up to four weeks prior to randomization; * pregnant or nursing patients; * prior radiotherapy to the pelvic region; * myocardial infarction up to six months prior to randomization, or uncontrolled ischemic heart disease; * congestive heart insufficiency New York Heart Association (NYHA) III-IV.