Tumor Necrosis Factor

Uses

Tumor Necrosis Factor is a tumor necrosis factor alpha used along with surgery to remove soft tissue sarcomas of the limbs.

For use in adults as an adjunct to surgery for subsequent removal of the tumour so as to prevent or delay amputation, or in palliative care, for irresectable soft tissue sarcoma of the limbs . Used in combination with melphalan via mild hyperthermic isolated limb perfusion.

Tumor Necrosis Factor is also used to associated treatment for these conditions: Soft Tissue Sarcoma (STS), Tumour excision

How Tumor Necrosis Factor works

Since tasonermin is recombinant TNF-α, it functions exactly as endogenous TNF-α does. The direct cytotoxic effect of TNF-α is mediated by TNF-α receptor 1 . The bound receptor activates the well-reviewed death receptor pathway involving the activation of initiator caspases 8 and 9 then ultimately ending in the activation of effector caspase 3 which begins the process of apoptosis.

The effect on tumor vasculature is mediated by the inflammatory signalling pathway of TNF-α, the NFκB pathway . This pathway is also activated by TNFR1 when bound to TNFα. The NFκB transcription factor increases expression of proteins in vascular endothelial cells. These proteins include cell adhesion molecules, inflammatory mediators like prostaglandins and interleukins, and growth factors . TNF-&alpha also increases the expression of inducible nitric oxide synthase via this pathway which contributes to the generation of reactive nitrogen species . These species are able to damage cells in the tumor and microvasculature.

The cytokines produced from NFκB activation and TNF-&aplha; itself serve to activate the cells of the immune system which further damage tumor cells with respiratory bursts, phagocytosis and subsequent breakdown of the cell, and release of cytotoxic enzymes. The antigen presenting cells which phagocytose the tumor cells are able to activate lymphocytes and allow the adaptive immune system to further damage the tumor tissue .

Toxicity

In addition to its intended cytotoxic effects, tasonermin produces secondary adverse effects.

Studies in mice, rats, dogs, monkeys, and rabbits observed hematological changes including anemia, increased hematocrit, and changes in leukocyte and platelet counts dependent on species and treatment duration .

Tumor Necrosis Factor also produces decreases in blood pressure. Increases in heart rate and reductions in cardiac contractility have been noted in some studies.

Increased liver enzymes suggest altered liver function as a result of tasonermin administration. Changes in kidney function have also been observed including increased water and sodium excretion as well as increased serum urea and creatinine.

The only study to determine a no observable adverse effect level found the value to be 0.1 μg/kg in monkeys during a 7-day course of tasonermin.

Food Interaction

Volume of Distribution

The estimated volume of distribution varies with the dose administered with intravenous doses of 35 μg/m² and 150 μg/m² producing values of 55 L and 17 L respectively .

Elimination Route

No absorption data is available. No enteral route formulation exists for tasonermin.

Half Life

Tumor Necrosis Factor has a terminal half life of 20-30 min at doses of 150 μg/m² . This value increases as dosage increases.

Clearance

Clearance was estimated to be 2 L/min and 0.5 L/min after intravenous doses of 35 μg/m² and 150 μg/m² respectively . This value decreases as dosage increases.

Elimination Route

No data is available on route of elimination.

Innovators Monograph

You find simplified version here Tumor Necrosis Factor