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Unchanged glutamate or glutamine is consistent with a properly functioning citric acid cycle because the enzymes involved in -ketoglutarate metabolism (isocitrate dehydrogenase and -ketoglutarate dehydrogenase complex) are key pathway regulators and therefore a disruption in the cycle would be reflected in changes in -ketoglutarate and its equilibrium with glutamateglutamine

The main drawbacks involve needle discomfort, potential injection site reactions, and the requirement for sterile technique

Everolimus is approved for advanced renal cell carcinoma on the basis of improved progression-free survival in a phase III trial (NCT00410124)