Reduced glutathione (GSH) has been reported to be an effective protector against cyclophosphamide-induced urotoxicity in experimental models, providing protection comparable to that of mesna. This paper describes our preliminary results of the clinical use of GSH in combination with cyclophosphamide. GSH was administered i.v. in two divided doses of 2.5 g, 15 min before and 30 min after escalating doses of cyclophosphamide ranging from 1.2 up to 1.6 g/m2 (1-h infusion). GSH was well tolerated and did not produce unexpected toxicity. The lack of bladder damage, including microscopic hematuria, supports the protective role of this thiol compound.
Get full access to this article
View all access options for this article.
References
1.
BohmS., OrianaS., SpattiG.B., TognellaS., TedeschiM., ZuninoF., Di ReF.: A clinical study of reduced glutathione as a protective agent against cisplatin-induced toxicity. In: Platinum and other metal coordination compounds in cancer chemotherapy.NicoliniM. (ed.), pp. 456–459, Martinus Nijhoff Publishing, Boston, 1988.
2.
BradeW., SeeberS., HerdrichK.: Comparative activity of ifosfamide and cyclophosphamide.Cancer Chemother. Pharmacol., 18(Suppl. 2): S1–S9, 1986.
3.
BrockN., PohlJ., StekarJ.: Studies on the urotoxicity of oxazaphosphorine cytostatic and its prevention. I. Experimental studies on the urotoxicity of alkylating compounds.Europ. J. Cancer, 17: 595–607, 1981.
4.
CavallettiE., TofanettiO., ZuninoF.: Comparison of reduced glutathione with 2-mercaptoethane sulfonate to prevent cyclophosphamide-induced urotoxicity.Cancer Letters, 32: 1–6, 1986.
5.
ColvinM., HiltonJ.: Pharmacology of cyclophosphamide and metabolites.Cancer Treat. Rep., 65(Suppl. 3): 89–95, 1981.
6.
CoxP.J.: Cyclophosphamide cystitis - identification of acrolein as the causative agent.Biochem. Pharmacol., 28: 2045, 1979.
7.
HansenH.H., MuggiaF.M., SainiN.: Cyclophosphamide and the urinary bladder.N. Engl. J. Med., 284: 1043, 1971.
8.
HowsJ.M., MehtaA., WardL., WoodsK., PerezR., GordonM.Y., Gordon-SmithE.C.: Comparison of mesna with forced diuresis to prevent cyclophosphamide induced haemorrhagic cystitis in marrow transplantation: a prospective randomised study.Br. J. Cancer, 50: 753–756, 1984.
9.
LangE., GoosM.: Hypersensitivity to Mesna.Lancet, 2: 329, 1985.
10.
MeanwellC.A., BlakeA.E., KellyK.A., HonigsbergerL., BlackledgeG.: Prediction of ifosfamide/mesna associated encephalopathy.Eur. J. Cancer Clin. Oncol., 22: 815–819, 1986.
11.
MendelsonD., BlockJ.B., SerpickA.A.: Effect of large intermittent intravenous doses of cyclophosphamide in lymphoma.Cancer, 25: 715–720, 1970.
12.
ShawI.C., GrahamM.I.: Mesna - a short review.Cancer Treat. Rev., 14: 67–86, 1987.
13.
TofanettiO., CavallettiE., BesatiA., PratesiG., PezzoniG., ZuninoF.: Prevention of cyclophosphamide-induced urotoxicity by reduced glutathione and its effect on acute toxicity and antitumor activity of the alkylating agent.Cancer Chemother. Pharmacol., 14: 188–193, 1985.
