ATC Group: V03AF Detoxifying agents for antineoplastic treatment

Amifostine is a prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite. This metabolite is believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues.

Calcium folinate is an active metabolite of folinic acid and essential coenzyme for nucleic acid synthesis in cytotoxic therapy. Calcium folinate is frequently used to diminish the toxicity and counteract the action of folate antagonists, such as methotrexate.

Dexrazoxane has two major mechanisms of action, chelation of iron and inhibition of topoisomerase II. It is not known to what extent each of these mechanisms contributes to the preventive effect on tissue destruction following anthracycline extravasation.

Glucarpidase is a recombinant bacterial enzyme that hydrolyses the carboxyl-terminal glutamate residue from folic acid and structurally related molecules such asMTX. Glucarpidase converts MTX to its inactive metabolites DAMPA and glutamate.

Levoleucovorin is the pharmacologically active isomer of 5-formyltetrahydrofolic acid. Administration of levoleucovorin can “rescue” normal cells and thereby prevent toxicity of folic acid antagonists such as methotrexate which act by inhibiting dihydrofolate reductase.

Mesna is an antidote, and offers the possibility of reliably preventing urotoxic side-effects associated with aggressive cancer chemotherapy using oxazaphosphorine cytostatics.

Rasburicase is a highly potent uricolytic agent that catalyses enzymatic oxidation of uric acid into allantoin, a water soluble product, easily excreted by the kidneys in the urine.

Sodium folinate is a reduced derivative of folic acid. Sodium folinate is mainly used for colorectal cancer treatment in association with 5-fluorouracil and Oxaliplatin (FOLFOX regimen) or with 5-fluorouracil and Irinotecan (FOLFIRI regimen). Additionally, it is administered as salvage therapy to reduce toxic effects following high doses of methotrexate in the treatment of some neoplastic diseases, rheumatoid arthritis or severe psoriasis. Sodium folinate is also given to treat anemia caused by folate deficiency.

Sodium levofolinate is the pharmacologically active isomer of 5-formyl tetrahydrofolic acid. Sodium levofolinate does not require reduction by dihydrofolate reductase to participate in reactions utilizing folates as a source of “one-carbon” moieties. Administration of levoleucovorin counteracts the therapeutic and toxic effects of folic acid antagonists such as methotrexate, which act by inhibiting dihydrofolate reductase.