BACKGROUND
pneumonitis, nausea/vomiting, fatigue, abdominal pain, cancer, toxicities, malignancies, cancer deaths, tumors
PNEUMONITIS, CANCER, THROMBOCYTOPENIA, MALIGNANCIES, TUMORS, TYPE II DIABETES
Solid tumors, including central nervous system (CNS) tumors, represent approximately 60% of all childhood malignancies and account for the majority of cancer deaths in children.Irinotecan and temozolomide are frequently used in pediatric solid and CNS tumors due to clinical tolerability and preclinical evidence of synergy.Metformin is an FDA‐approved oral biguanide used to treat type II diabetes. An international randomized placebo‐controlled trial showed metformin was safe and effective in children 12 and older, with main side effects of abdominal pain and nausea/vomiting.Phase I studies of metformin alone and in combination with other agents in adults with cancer have found a wide range of tolerable metformin doses as high as 2000 mg/day. However in one study in combination with temsirolimus, the starting dose level was not tolerated due to dose limiting toxicities of pneumonitis, fatigue and thrombocytopenia, requiring a dose reduction of temsirolimus and a maximum metformin dose of only 500 mg/day.