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.