Abstract
Otto Warburg observed in 1924 that cancer cells were dependent exclusively on glycolysis for the production of energy even in the presence of oxygen (the 'Warburg effect'). Consequently, cancer cells require ~19 times more glucose uptake to obtain equivalent amounts of energy as normal cells. The Warburg effect is the scientific basis for positron emission tomography (PET), which has markedly improved cancer detection. During chemotherapy, cancer cells may upregulate their expression of multi-drug resistance proteins and ultimately cause treatment failure. As multi-drug resistance proteins require energy to operate, the present report evaluated the potential clinical efficacy of lowering blood glucose with insulin during chemotherapy for a patient with advanced pulmonary adenocarcinoma with multiple metastases. A 64-year-old male was admitted to the Department of Medical Oncology at Changzhou Tumor Hospital (Changzhou, China) due to an irritating cough and multiple bone pain. PET/computed tomography (CT) with F-18 fluorodeoxy glucose (18F-FDG) identified multiple hypermetabolic foci in the right hilum, right upper lung, shoulder blades, thoracic vertebrae, lumbar, sacrum, bilateral iliac crest and pelvis. Additionally, magnetic resonance imaging detected multiple metastases in the brain. The patient received 56 repeat treatments with insulin to induce hypoglycemia combined with reduced doses of chemotherapy over an 8-month period. For each treatment, insulin at 0.2 U/kg body weight was injected intravenously (i.v.), and when blood glucose level reached 2.5-3.0 mmol/l, navelbine (10 mg), cisplatin (10 mg) and fluorouracil (250 mg) were injected (i.v.) over a period of ~10 min. The patient's blood glucose level was returned to normal immediately after chemotherapy with an i.v. injection of 20 ml 50% glucose solution. During the 8-month chemotherapy regimen, the patient received two PET/CT follow-ups. The results demonstrated that the levels of 18F-FDG uptake in all lesions had been reduced. In addition, the patient exhibited improved appetite and weight gain, a reduced cough, and had less pain. The levels of tumor markers, namely carcinoembryonic antigen, carcinoma antigen 15-3, CYRA21-1, neuron-specific enolase, also declined gradually. These results suggest that controlled, mild hypoglycemia may be safely combined with low dose chemotherapy to provide clinical benefit for advanced non-small cell lung cancer.