Lung tumour growth delay and normal tissue toxicity induced by three cytotoxic platinum drugs.
Single doses of the drug cisplatin and its analogues carboplatin and iproplatin were administered to tumour-bearing rats. The tumours used were two bronchial squamous cell carcinomas, that are part of a panel of experimental lung tumours developed at this institute. Cisplatin resulted in severe nephrotoxicity. Carboplatin and iproplatin were less nephrotoxic, but resulted in acute gastrointestinal and (probably) hematological toxicity. Carboplatin also caused late occurring liver damage. The responses of the tumours were compared at the level of maximum tolerated drug doses for early toxicity. The level of response was different for the two tumours. One was more sensitive to the drugs than the other. The effects of cisplatin and carboplatin were approximately similar. Iproplatin was less effective. Because cisplatin caused more severe late toxicity, it is concluded that carboplatin has the best therapeutic index for these two lung tumours.
van Rongen
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TNO Institute of Applied Radiobiology and Immunology, Rijswijk, The Netherlands.
Kal
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Kuijpers
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WC
van Berkel
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AH
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D016190:Carboplatin / Q000627:therapeutic use* / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D002945:Cisplatin / Q000627:therapeutic use* / Q000633:toxicity; D004064:Digestive System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007668:Kidney / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000627:therapeutic use* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C023359:iproplatin; D016190:Carboplatin; D002945:Cisplatin