Knowledge about how anticancer drugs work has stimulated the search for drugs that counteract toxicities (protectors) or enhance their effectiveness (potentiators).
• Protectors include the thiol amifostine, other thiols including glutathione, dexrazoxane and the
colony-stimulating factors.
• Potentiators—also named modulators—include buthionine sulfoximine (BSO), L-leucovorin, dipyridamole and
drugs such as cyclosporin and its derivatives that reverse multi-drug resistance .
Amifostine (Ethyol, WR2721) is under study by US Bioscience as a protector against the bone marrow toxicity of cisplatin and cyclophosphamide and possibly as a protector against some other toxic effects of cisplatin, such as those on the nerves and kidney. Antitumor effects appear to be unchanged. Vomiting and low blood pressure are its principal side effects.
Buthionine sulfoximine (BSO) is under investigation as a drug to deplete glutathione and make alkylating drugs such as melphalan or platinum derivatives more effective.
Cyclosporin A analogues that do not suppress the immune system are undergoing testing to reverse multi-drug resistance. We have improved our ability to identify tumors that have become resistant by expression of the gene named MDR. Many drugs of various kinds are being tested to counteract this resistance, but the restoration of drug effectiveness has yet to be shown convincingly.
