Insulin and Diazoxide for Treatment of Cancer

Abstract

Insulin is a growth stimulating hormone for several malignant tumors. In experimental breast cancer, diabetes induction with alloxan, strep-tozotocin or diazoxide leads to remission and intensifies the effect of an ovariectomy and of antiestrogen treatment. Clinically, in one of nine breast cancer patients, a partial remission of dermal metastases of seven months duration was achieved following a tamoxifen-induced remission by additional treatment with 200 mg diazoxide daily. In two other breast cancer patients, diazoxide led to stable disease of four (monotherapy) and eight months duration. Increased insulin levels can enhance the effect of simultaneous cytostatic therapy in a number of experimental systems. Initial clinical trials of combined therapy with methotrexate (MTX)/5-fluorouracil (5FU) and glucose/insulin indicate an increased cytostatic effect of this combination in some patients with breast cancer and in two patients with colon cancer, who were both pretreated with the same MTX/5FU regimen without glucose/insulin. In a case treated with high dose methotrexate therapy, the decrease of serum MTX-levels was slightly accelerated during and markedly delayed after the end of the glucose/ insulin-infusion.

Diazoxide for Lowering Insulin Levels in Breast Cancer Patients

“…Another 2 months later, the patient exhibited a rebound response of 4 months duration with the disappearance of pleural effusions, partial remission of the cutaneous metastases, and stable size of the liver metastases. In two additional patients with prior disease progress, diazoxide treatment resulted in stable disease of 8 (combined with tamoxifen) and 4 (monotherapy) months [4].We think that diazoxide is an underrated drug for studies on cancer treatment because it lowers insulin and IGF-1 levels. While hyperglycemia correlates with poor outcomes in cancer patients [2], this side effect could be overcome by combining the drug with (a) acarbose, which completely inhibited mammary carcinogenesis in rats [5]; (b) carbohydrate restriction, which by itself could retard tumor growth [6]; and (c) medium chain triglycerides and exogenous ketone bodies, which rapidly elevate ketone body levels while decreasing blood glucose concentration [7].…”

“…Another 2 months later, the patient exhibited a rebound response of 4 months duration with the disappearance of pleural effusions, partial remission of the cutaneous metastases, and stable size of the liver metastases. In two additional patients with prior disease progress, diazoxide treatment resulted in stable disease of 8 (combined with tamoxifen) and 4 (monotherapy) months [4].…”

“…This effect was completely abolished by additional treatment with 2 IU depot insulin per day, and, thus, an insulin-mediated effect of diazoxide was proven [3]. Adding 200 mg/kg diazoxide synergistically prolonged the remission duration induced by different tamoxifen doses by about 50% [2].In a clinical pilot study with nine breast cancer patients, diazoxide was used at a dose of 200-300 mg per day [4]. For inclusion, maximal tolerated fasting glucose level was 110 mg/ dL, and 180 mg/dL after an oral glucose load with 75 g. The best response was seen in a 60-year-old woman, who had glucose levels of only 56-105-115 mg/dL in the oral glucose load test.…”

“…In a clinical pilot study with nine breast cancer patients, diazoxide was used at a dose of 200-300 mg per day [4]. For inclusion, maximal tolerated fasting glucose level was 110 mg/ dL, and 180 mg/dL after an oral glucose load with 75 g. The best response was seen in a 60-year-old woman, who had glucose levels of only 56-105-115 mg/dL in the oral glucose load test.…”