A Review of the Modulation of Cisplatin Toxicities by Chemoprotectants

  • Robert T. Dorr

Abstract

In 1988, Dr. Brian Leyland-Jones questioned “Whither the Modulation of Platinum” in an editorial in the Journal of the National Cancer Institute (Leyland-Jones, 1988). The quest for specific chemoprotectants clearly predates the advent of platinum-based chemotherapy and yet, progress has been slow with only a few chemoprotectants available in the clinic. These include mesna for the oxazophosphorines (Shaw, 1987), amifostine for cisplatin (in certain European countries), and more recently, the cardioprotectant iron chelator, cardioxane (ADR-529 or ICRF-187) [Speyer et al., 1988 and 1992]. For the platinum-based antitumor agents, a large number of thiol-based or sulfur-containing nucleophiles have been tested. These include the endogenous tripeptide glutathione, disulfiram and its metabolite, diethyldithiocarbamate, the inorganic salt, sodium thiosulfate, and the phosphorylated aminothiol, amifostine (Ethyol or WR-2721) (Glover et al., 1987) (Figure 1). Of these, several appear to have promise for clinical utility against platinum-induced nephrotoxicity and possibly the peculiar cumulative-dose limiting neuropathy. For this condition, a unique melanocortin-derived neuropeptide, ORG-2766, appears to have potential utility.

Keywords

Placebo Toxicity Platinum Cyclophosphamide Thrombocytopenia 

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References

  1. Aamdal S., Fedstad O., and Pihl A., 1988, Sodium thiosulfate fails to increase the therapeutic index of intravenously administered cis-diammine-dichloroplatinum (II) in mice bearing murine and human tumors, Cancer Chemother Pharmacol 21:129.PubMedCrossRefGoogle Scholar
  2. Andrews P.A., and Howell S.B., 1990, Cellular pharmacology of cisplatin: perspectives on mechanisms of acquired resistance, Cancer Cells, 2(2):35.PubMedGoogle Scholar
  3. Andrews P.A., Murphy M.P., and Howel S.B., 1985, Differential potentiation of alkylating and platinating agent cytotoxicity in human ovarian carcinoma cells by glutathione depletion, Cancer Res. 30:643.Google Scholar
  4. Asta-Werke Degussa Pharma Grouppe, 1984, Uromitexan (mesna) uroprotector, basic information, Bielefeld, FRG.Google Scholar
  5. Baskin S.I., Horowitz A.M., and Nealley E.W., 1992, The antidotal action of sodium nitrite and sodium thiosulfate against cyanide poisoning, J Clin Pharmacol 32:368.PubMedCrossRefGoogle Scholar
  6. Berry J.M., Jacobs C., Sikic B., et al, 1990, Modification of cisplatin toxicity with diethyldithiocarbamate, J Clin Oncol 8:1585.PubMedGoogle Scholar
  7. Bodenner D.I., Dedon P.C., Keng P.C., et al., 1986, Effect of diethyldithiocarbamate (DDTC) on cis-diamminedichloroplatinum (II)-induced cytotoxicity, DNA cross-linking and gamma-glutamyl transpeptidase inhibition, Cancer Res. 46:2745.PubMedGoogle Scholar
  8. Bohm S., Spatti G., De Re F., et al., 1991, A feasibility study of cisplatin administration with low-volume hydration and glutathione protection in the treatment of ovarian carcinoma, Anticancer Res. 11:1613.PubMedGoogle Scholar
  9. Bonadonna G., and Karnofsky D.A., 1965, Protection studies with sodium thiosulfate against methyl bis (β-chloroethyl)amine hydrochloride (HN2) and its ethylenimonium derivative, Clin Pharmacol Ther. 6(1):50.PubMedGoogle Scholar
  10. Borch R.F., and Pleasants M.E., 1979, Inhibition of cis-platinum nephrotoxicity by diethyldithiocarbamate rescue in a rat model, Proc Natl Acad Sci USA. 76(12):6611.PubMedCrossRefGoogle Scholar
  11. Borch R.F., Katz J.C., Lieder P.H., and Pleasants M.E., 1980, Effect of diethyldithiocarbamate rescue on tumor response to cis-platinum in a rat model, Proc Natl Acad Sci USA. 77(9):5441.PubMedCrossRefGoogle Scholar
  12. Burchenal J.H., Kalaher K., Dew K., et al., 1978, Studies of cross-resistance, synergistic combinations and blocking of activity of platinum derivatives, Biochimie. 60:961.CrossRefGoogle Scholar
  13. Cascinu S., Cordelia L., Del Ferro E., et al., 1995, Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial, J Clin Oncol. 13(1):26.PubMedGoogle Scholar
  14. Cavaletti G., Tredici G., Pizzini G., et al., 1992, Morphologic, morphometric and toxicologie evaluations of the effect of cisplatin alone or in combination with glutathione on the rat nervous system, Clin Neuropathol. 11:169.Google Scholar
  15. Cersosimo R.J., 1989, Cisplatin neurotoxicity, Cancer Treat Rep. 16:195.CrossRefGoogle Scholar
  16. Cohen J.D., and Robins H.I., 1990, Cytotoxicity of diethyldithiocarbamate in human versus rodent cell lines, Invest New Drugs. 8:137.PubMedCrossRefGoogle Scholar
  17. Colombo N., Bird S., Miceli D., et al., 1995, Weekly cisplatin ± glutathione in relapsed ovarian carcinoma, Int J Gynecol Cancer. 5:81.PubMedCrossRefGoogle Scholar
  18. Cozzaglio L., Doci R., Colla G., et al., 1990, A feasibility study of high-dose cisplatin and 5-fluorouracil with glutathione protection in the treatment of advanced colorectal cancer, Tumori. 76:590.PubMedGoogle Scholar
  19. De Re F., Bohm S., Oriana S., et al., 1993, High-dose cisplatin and cyclophosphamide with glutathione in the treatment of advanced ovarian cancer, Ann Oncol. 4:55.PubMedGoogle Scholar
  20. De Wied D., and Jolies J., 1982, Neuropeptides derived from pro-opiocortin: behavioral, physiological and neurochemical effects, Physiol Rev. 62:976.PubMedGoogle Scholar
  21. de Koning P., Neijt J.P., Jennekens F.G.I., and Gispen W.H., 1987, Org.2766 protects from cisplatin-induced neurotoxicity in rats, Exper Neurol. 97:746.CrossRefGoogle Scholar
  22. de Sauvage F.J., Hass P.E., Spencer S.D., et al., Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand, Nature. 369:533.Google Scholar
  23. Dedon P.C., and Borch R.F., 1987, Characterization of the reactions of platinum antitumor agents with biologic and nonbiologic sulfur-containing nucleophiles, Biochem Pharmacol. 36:1955.PubMedCrossRefGoogle Scholar
  24. DeGregorio M.W., Gandara D.R., Holleran W.M., et al, 1989, High-dose cisplatin with diethyldithiocarbamate (DDTC) rescue therapy: preliminary pharmacologie observations, Cancer Chemother Pharmacol. 23:276.PubMedCrossRefGoogle Scholar
  25. Di Re F., Bohm S., Oriana S., et al., 1990, Efficacy and safety of high-dose cisplatin and cyclophosphamide with glutathione protection in the treatment of bulky advanced epithelial ovarian cancer. Cancer Chemother Pharmacol. 25:355.PubMedCrossRefGoogle Scholar
  26. Dible S.E., Siddik Z.H., Boxall F.E., et al., 1987, The effect of diethyldithiocarbamate on the haematological toxicity and antitumor activity of carboplatin, Eur J Cancer Clin Oncol. 23:813.PubMedCrossRefGoogle Scholar
  27. Doroshow J.H., Locker G., Ifrim I., et al, 1981, Prevention of doxorubicin cardiac toxicity in the mouse by N-acetylcysteine, J Clin Invest. 64:1053.CrossRefGoogle Scholar
  28. Doroshow J.H., Locker G.Y., and Myers C.E., 1980, The enzymatic defenses of the mouse heart against oxygen metabolites, J Clin Invest. 65:128.PubMedCrossRefGoogle Scholar
  29. Dorr R.T., and Lagel L., 1989, Interaction between cisplatin and mesna in mice. J Cancer Res Clin Oncol. 115:604.PubMedCrossRefGoogle Scholar
  30. Dorr R.T., Soble M., and Alberts D.S., 1988, Efficacy of sodium thiosulfate as alocal antidote to mechlorethamine skin toxicity in the mouse, Cancer Chemother Pharmacol 22:299.PubMedCrossRefGoogle Scholar
  31. Elderson A., van der Hoop G.P., Haanstra W., et al., 1989, Vibration perception and thermoperception as quantitative measurements in the monitoring of cisplatin-induced neurotoxicity, J Neurol Sci. 93:167.PubMedCrossRefGoogle Scholar
  32. Evans R.G., Wheatley C., Engel C., et al, 1984, Modification of the bone marrow toxicity of cis-diamminedichloroplatinum(II) in mice by diethyldithiocarbamate, Cancer Res. 44:3686.PubMedGoogle Scholar
  33. Filipski J., Kohn K.W., Prather R., and Bonner W.M., 1979, Thiourea reverses cross-links and restroes biological activity in DNA treated with dichlorodiaminoplatinum(II), Science. 204:181.PubMedCrossRefGoogle Scholar
  34. Fontanelli R., Spatti G., Raspagliesi F., et al., 1992, A preoperative single course of high-dose cisplatin and bleomycin with glutathione protection in bulky stage IB/n carcinoma of the cervix, Ann Oncol. 3:117.PubMedCrossRefGoogle Scholar
  35. Francis P., Markman M., Hakes T., et al., 1989, Diethyldithiocarbamate chemoprotection of carboplatin-induced hematological toxicity, J Cancer Res Clin Oncol. 119:360.CrossRefGoogle Scholar
  36. Freeman M.L., and Meredith M.J., 1989, The relationship between intracellular glutathione concentration and cisplatin cytotoxicity, Proc Amer Assoc Cancer Res. 30:460.Google Scholar
  37. Friedman H.S., Colvin O.M., Aisaka K., et al., 1990, Glutathione protects cardiac and skeletal muscle from cyclophosphamide-induced toxicity, Cancer Res. 50:2455.PubMedGoogle Scholar
  38. Gale G.R., Atkins L.M., and Walker, Jr., E.M., 1982, Further evaluation of diethyldithiocarbamate as an antagonist of cisplatin toxicity, Ann Clin Lab Sci. 12(5):345.PubMedGoogle Scholar
  39. Gandara D.R., Nahhas W.A., Adelson M.D., et al., 1995, Randomized placebo-controlled multicenter evaluation of diethyldithiocarbamate for chemoprotection against cisplatin-induced toxicities, J Clin Oncol. 13(2):490.PubMedGoogle Scholar
  40. Glover D., Glick J.H., Weiler C., et al., 1987, WR-2721 and high-dose cisplatin: an active combination in the treatment of metastatic melanoma, J Clin Oncol. 5:574.PubMedGoogle Scholar
  41. Goel R., Cleary S.M., Horton C., et al., 1989, Effect of sodium thiosulfate on the pharmacokinetics and toxicity of cisplatin, J Natl Cancer Inst. 81:1552.PubMedCrossRefGoogle Scholar
  42. Goldberg J.M., and Lindblom U., 1979, Standardised method of determining vibratory perception thresholds for diagnosis and screening in neurological investigation, J Neurol Neurosurg Psychiatry. 42:793.PubMedCrossRefGoogle Scholar
  43. Gonias S.L., Oakley A.C., Walther P.J., and Pizzo S.V., 1984, Effects of diethyldithiocarbamate and nine other nucleophiles on the intersubunit protein cross-linking and inactivation of purified human α2-macroglobulin by cis-diamminedichloroplatinum(II), Cancer Res. 44:5764.PubMedGoogle Scholar
  44. Gregg R.W., Molepo J.M., Monpetit V.J.A., et al., 1992, Cisplatin neurotoxicity: the relationship between dosage, time, and platinum concentration in neurologic tissues, and morphologic evidence of toxicity, J Clin Oncol. 10(5):795.PubMedGoogle Scholar
  45. Griffith O.W., and Meister A., 1979, Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine), J Biol Chem. 254:7558.PubMedGoogle Scholar
  46. Hacker M.P., Ershler W.B., Newman R.A., and Gamelli R.L., 1982, Effect of disulfiram (tetraethylthiuram disulfide) and diethyldithiocarbamate on the bladder toxicity and antitumor activity of cyclophosphamide in mice, Cancer Res, 42:4490.PubMedGoogle Scholar
  47. Halonen P., 1986, Quantitative vibration perception thresholds in healthy subjects of working age, Eur J Appl Physiol. 54:647.CrossRefGoogle Scholar
  48. Hamers F.P.T., Gispen W.H., and Neijt J.P., 1991, Neurotoxic side-effects of cisplatin, Eur J Cancer. 27:372.CrossRefGoogle Scholar
  49. Hamers F.P.T., Brakkee J.H., Cavalletti E., et al., 1993a, Reduced glutathione protects against cisplatin-induced neurotoxicity in rats, Cancer Res. 53:544.PubMedGoogle Scholar
  50. Hamers F.P.T., Pette C., Bravenboer B., et al., 1993b, Cisplatin-induced neuropathy in mature rats: effects of the melanocortin-derived peptide ORG 2766, Cancer Chemother Pharmacol 32:162.PubMedCrossRefGoogle Scholar
  51. Hamilton T.C., Winker M.A., Louis K.G., et al., 1985, Augmentation of adriamycin, melphalan and cisplatin cytotoxicity in drug-resistant and-sensitive human ovarian carcinoma cell lines by buthionine sulfoximine mediated glutathione depletion, Biochem Pharmacol. 34:2583.PubMedCrossRefGoogle Scholar
  52. Hovestadt A., Van der Burg M.E.L., Verbiest H.B.C., et al., 1992, The course of neuropathy after cessation of cisplatin treatment, combined with ORG 2766 or placebo, J Neurol. 239:143.PubMedCrossRefGoogle Scholar
  53. Howell S.B., and Taetle R., 1980, Effect of sodium thiosulfate on cis-dichlorodiammineplatinum(II) toxicity and antitumor activity in L1210 leukemia, Cancer Treat Rep. 64(4–5):611.PubMedGoogle Scholar
  54. Howell S.B., Pfeifle C.E., Wung W.E., and Olshen R.A., 1982, Intraperitoneal chemotherapy with cisplatin, Proc Am Soc Clin Oncol. 1:27.Google Scholar
  55. Howell S.B., Pfeifle C.E., Wung W.E., and Olshen R.A., 1983, Intraperitoneal cis-diamminedichloroplatinum with systemic thiosulfate protection, Cancer Res. 43:1426.PubMedGoogle Scholar
  56. Leone R., Fracasso M.E., Soresi E., et al., 1992, Influence of glutathione administration on the disposition of free and total platinum in patients after administration of cisplatin, Cancer Chemother Pharmacol 29:385.PubMedCrossRefGoogle Scholar
  57. Lerza R., Bogliolo G., Muzzulini C., and Pannacciulli I., 1986, Failure of N-acetylcysteine to protect against cis-dichlorodiammineplatinum(II)-induced hematopoietic toxicity in mice, Life Sci Rev. 38(19):1795.CrossRefGoogle Scholar
  58. Leyland-Jones B., 1988, Whither the modulation of platinum?, J Natl Cancer Inst. 80(18):1432.PubMedCrossRefGoogle Scholar
  59. Leyland-Jones B., Deesen P., Reidenberg M.M., et al., 1980, Amelioration of cisplatin renal and gastrointestinal toxicity by N-acytylcysteine in rats, Clin Res. 28:622A.Google Scholar
  60. Leyland-Jones B., Morrow C., Tate S., et al., 1983, cis-Diamminedichloro platinum (II) nephrotoxicity and its relationship to renal γ-glutamyl transpeptidase and glutathione, Cancer Res. 43:6072.PubMedGoogle Scholar
  61. Litterest C.L., Bertolero F., and Uozumi J., 1986, The role of glutathione and metallothionein in the toxicity and subcellular binding of cisplatin: In: MCBrain D.C.H., and Slater T.F. (eds) Biochemical mechanism of platinum antitumor drugs, IRL Press, Oxford p 227.Google Scholar
  62. Litterst C.L., Tong S., Hirokata Y., and Siddik Z.H., 1982, Alteration in hepatic and renal levels of glutathione and activities of glutathione S-transferases from rats treated with cis-dichlorodiammine platinum-II, Cancer Chemother Pharmacol 8:67.PubMedCrossRefGoogle Scholar
  63. Maines M.D., 1986, Differential effect of cis-platinum on regulation of liver and kidney haem and haemoprotein metabolism, Biochem J. 237:713.PubMedGoogle Scholar
  64. Mayer R.D., and Maines M.D., 1990, Promotion of fnms-platinum in vivo effects on renal heme and hemoprotein metabolism by D,L-buthionine-S,R-sulfoximine, Biochem Pharmacol 39(10):1565.PubMedCrossRefGoogle Scholar
  65. Mayer R.D., Lee K., and Cockett A.T.K., 1987, Inhibition of cisplatin induced nephrotoxicity in rats by buthionine sulfoximine, a glutathione synthesis inhibitor, Cancer Chemother Pharmacol 20:207.PubMedCrossRefGoogle Scholar
  66. Meister A., Tate S. S., and Griffith O. W., 1981, γ-Glutamyl trans-peptidase, Methods Enzymol. 77:237.PubMedCrossRefGoogle Scholar
  67. Müller L.J., van der Hoop R.G., Moorer-van Delft CM, et al., 1990, Morphological and electrophysiological study of the effects of cisplatin and ORG · 2766 on rat spinal ganglion neurons, Cancer Res. 50:2437.PubMedGoogle Scholar
  68. Neijt J., Van der burg M., Vecht C., et al., 1994, A double-blind randomised study with ORG-2766, an ACTH (4-9) analog, to prevent cisplatin neuropathy, Proc Am Soc Clin Oncol 13:261.Google Scholar
  69. O’Dwyer P.J., Hamilton T.C., Young R.C., et al, 1992, Depletion of glutathione in normal and malignant human cells in vivo by buthionine sulfoximine: Clinical and biochemical results, J Natl Cancer Inst 34:264.CrossRefGoogle Scholar
  70. Ongerboer de Visser B.W., and Tiessens G., 1985, Polyneuropathy induced by cisplatin, Prog Exp Tumor Res. 29:190.PubMedGoogle Scholar
  71. Owens G., and Hatiboglu I., 1961, Clinical evaluation of sodium thiosulfate, a systemic neutralizer of nitrogen mustard, Ann Surg. 154:895.PubMedGoogle Scholar
  72. Paredes J., Hong W.I., Felder T.B., et al., 1988, Prospective randomized trial of high dose cisplatin and fluorouracil infusion with or without sodium diethyldithiocarbamate in recurrent and/or metastatic squamous cell carcinoma of the head and neck, J Clin Oncol 6:955.PubMedGoogle Scholar
  73. Pfeifle C.E., Howell S.B., Felthouse R.D., et al, 1985, High-dose cisplatin with sodium thiosulfate protection, J Clin Oncol 3(2):237.PubMedGoogle Scholar
  74. Pirovano C., Balzarini A., Bohm S., et al., 1992, Peripheral neurotoxicity following high-dose cisplatin with glutathione: clinical and neurophysiological assessment, Tumori. 78:253.PubMedGoogle Scholar
  75. Powell A.K., 1954, Effect of dithiocarbamates on sarcoma cells and fibrocytes in vitro, Br J Cancer. 8:529.PubMedCrossRefGoogle Scholar
  76. Qazi R., Chang A.Y.C., Borch R.F., et al., 1988, Phase I clinical and pharmacokinetic study of diethyldithiocarbamate as a chemoprotector from toxic effects of cisplatin, J Natl Cancer Inst. 80:1486.PubMedCrossRefGoogle Scholar
  77. Renoux G., and Renoux M., 1984, Diethyldithiocarbamate (DTC). A biological augmenting agent specific for T cells, In: R.L. Fenichel and M.A. Chirigos (eds) Immune Modulation Agents and Their Mechanisms, Marcel Dekker, Inc., New York, 1984, p. 7.Google Scholar
  78. Rumack B.H., Peterson R.C., Koch G.G., and Amara I.A., 1981, Acetaminophen overdose: 662 cases with evaluation of oral acetylcysteine treatment, Arch Intern Med. 141:380.PubMedCrossRefGoogle Scholar
  79. Scheef W., Klein H.O., Brock N., et al., 1979, Controlled clinical studies with an antidote against the urotoxicity of oxazaphosphorines: preliminary results, Cancer Treat Rep. 63:501.PubMedGoogle Scholar
  80. Schmalbach T.K., and Borch R.F., 1990, Mechanism of diethyldithiocarbamate modulation of murine bone marrow toxicity, Cancer Res. 50:6218.PubMedGoogle Scholar
  81. Schnellmann R.G., and Mandell L.J., 1986, Multiple effects of presumed glutathione depletors on rabbit proximal tubule, Kidney Int. 29:858.PubMedCrossRefGoogle Scholar
  82. Shaw I.C., and Graham M.I., 1987, Mesna — a short review, Cancer Treat Rev. 14:67.PubMedCrossRefGoogle Scholar
  83. Shea M., Koziol J.A., and Howell S.B., 1984, Kinetics of sodium thiosulfate, a cisplatin neutralizer, Clin Pharmacol Ther. 35(3):419.PubMedCrossRefGoogle Scholar
  84. Slater T.F., Ahmed J., and Ibrahim S.A., 1977, Studies on the nephrotoxicity of cis-dichlorodiammine-platinum2+ and related substances, J Clin Hematol Oncol. 7:534.Google Scholar
  85. Soble M.J., and Dorr R.T., 1987, Lack of enhanced myelotoxicity with buthionine sulfoximine and sulfhydryl-dependent anticancer agents in mice, Res Commun Chem Pathol Pharmacol. 55(2):161.PubMedGoogle Scholar
  86. Spath A., and Tempel K., 1987, Diethyldithiocarbamate inhibits scheduled and unscheduled DNA synthesis of rat thymocytes in vitro and in vivo — dose-effect relationships and mechanisms of action, Chem-Biol Interact. 64:151.PubMedCrossRefGoogle Scholar
  87. Speer R.J., Ridgway H., Hall L.M., et al., 1975, Coordination complexes of platinum as antitumor agents, Cancer Chemother Rep. 59:629.PubMedGoogle Scholar
  88. Speyer J.L., Green M.D., Kramer, E., et al., 1988, Protective effect of the bispiperazinedione ICRF-187 against doxorubicin-induced cardiac toxicity in women with advanced breast cancer, N Engl J Med., 319:745.PubMedCrossRefGoogle Scholar
  89. Speyer J.L., Green M.D., Zeleniuch-Jacquotte A., et al., 1992, ICRF-187 permits longer treatment with doxorubicin in women with breast cancer, J Clin Oncol 10(1):117.PubMedGoogle Scholar
  90. Stewart D.J., Verma S., and Maroun J.A., 1987, Phase I study of the combination of disulfiram with cisplatin, Am J Clin Oncol 10(6):517.PubMedCrossRefGoogle Scholar
  91. Strand F.L., and Smith CM., 1986, LPH, ACTH, MSH and motor systems. In: De Wied D, Gispen WH, Wimersma Greidanus TjB (eds) Neuropeptides and Behavior, Pergamon Press, Oxford Vol. 1, p. 245.Google Scholar
  92. Sunderman F.W., 1971, The treatment of acute nickel-carbonyl poisoning with sodium diethyldithiocarbamate, Ann Clin Res. 3:182.PubMedGoogle Scholar
  93. Ten Bokkel Huinink W.W., Wanders J., and Dubbelman R., 1987, High dose carboplatin in refractory ovarian cancer: a phase II trial assessing the protective role against myelosuppression by diethyldithiocarbamate, Madrid: Eur Cancer Soc. 214.Google Scholar
  94. Trugman J., Hogenkamp H.P.C., Roelofs R., and Hrushesky W.J.M., 1985, Cisplatin neurotoxicity: failure to demonstrate vitamin B12 inactivation, Cancer Treat Rep. 69(4):453.PubMedGoogle Scholar
  95. Uozumi J., and Litterst C.L., 1986, The effect of sodium thiosulfate on subcellular localization of platinum in rat kidney after treatment with cisplatin, Cancer Let. 32:279.CrossRefGoogle Scholar
  96. Uozumi J., Ishizawa M., Iwamoto Y., and Baba T., 1984, Sodium thiosulfate inhibits cis-diamminedichloroplatinum (II) activity, Cancer Chemother Pharmacol 13:82.PubMedCrossRefGoogle Scholar
  97. van der Hoop R.G., de Koning P., Boven E., et al., 1988, Efficacy of the neuropeptide ORG.2766 in the prevention and treatment of cisplatin-induced neurotoxicity in rats, Eur J Cancer Clin Oncol 24(4):637.CrossRefGoogle Scholar
  98. van der Hoop R.G., Vecht C.J., van der Burg M.E.L., et al., 1990, Prevention of cisplatin neurotoxicity with an ACTH(4-9) analogue in patients with ovarian cancer, N Engl J Med. 322:89.PubMedCrossRefGoogle Scholar
  99. Zunino F., Pratesi G., Micheloni A., et al., 1989, Protective effect of reduced glutathione against cisplatin-induced renal and systemic toxicity and its influence on the therapeutic activity of the antitumor drug, Chem Biol Interact. 70:89.PubMedCrossRefGoogle Scholar
  100. Zunino F., Tofanetti O., Besati A., et al., 1983, Protective effect of reduced glutathione against cis-dichlorodiammine Pt(II)induced nephrotoxicity and lethal toxicity, Tumori. 69:106.Google Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Robert T. Dorr
    • 1
  1. 1.College of Medicine and The Arizona Cancer CenterThe University of ArizonaTucsonUSA

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