Evaluation of Clinical Safety of Combining Metformin With Anticancer Chemotherapy

Inclusion criteria

• Histologically or cytologically documented cancer; diagnosis of hepatocellular carcinoma may be made by characteristic radiographic and/or AFP findings 33;
• Intended treatment with, or currently being treated by anti-cancer chemotherapy in the adjuvant or advanced setting;
• Age 18 to 79;
• Adequate renal function (serum creatinine levels <1.5 mg/dL [males], <1.4 mg/dL [females]). If a subject does not meet these criteria, but does have an estimated creatinine clearance >= 60 ml/min using the Cockroft-Gault calculation, they will be allowed. The Cockroft-Gault formula is CrCl = (140-age) x weight(kg)÷(Cr x72), where CrCl = estimated creatinine clearance and Cr is plasma creatinine in mg/dL;
• Adequate hepatic parameters, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 x upper limit of normal (ULN), total bilirubin ≤ 1.5 x ULN, and alkaline phosphatase levels ≤ 2.5 x ULN;
• Must anticipate receiving at least 3 cycles (or treatment periods of at least 3-weeks) of chemotherapy;
• Ability to understand and willingness to sign a written informed consent document.

Exclusion criteria

• Current use of metformin (within 1 week of start of chemotherapy regimen to be assessed);
• Patients with type 2 diabetes are allowed, however they will be excluded if there is intent to use metformin for treatment of diabetes during the course of the study;
• Undergoing chemotherapy treatment concurrent with radiation therapy;
• Undergoing chemotherapy in a neoadjuvant setting prior to potentially curative surgery;
• Renal disease or renal dysfunction not meeting inclusion criteria;
• Significant medical conditions such as cardiovascular collapse (shock), acute myocardial infarction, septicemia, acute or chronic metabolic acidosis;
• History of, or states associated with, lactic acidosis such as shock or pulmonary insufficiency, alcoholism (acute or chronic), conditions associated with hypoxemia and pancreatitis;
• Severe dehydration;
• Clinical or laboratory evidence of hepatic disease;
• Congestive heart failure requiring pharmacologic treatment, or unstable or acute congestive heart failure;
• Known hypersensitivity to metformin hydrochloride;
• Pregnant or lactating women (serum pregnancy test will be performed for all women of child-bearing potential);
• Psychiatric illness or social situation that would limit compliance with study requirements and/or obscure results