A Review of the Modulation of Cisplatin Toxicities by Chemoprotectants

  • Robert T. Dorr


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.


Clin Oncol Buthionine Sulfoximine Vibration Perception Threshold Total Platinum Tetraethylthiuram Disulfide 
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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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