Therapeutic evaluation of five nitrosoureas in a human melanoma xenograft system

✍ Scribed by Rainhardt Osieka; Peter Glatte; Rita Pannenbäcker; Carl Gottfried Schmidt

• Book ID: 104684528
• Publisher: Springer
• Year: 1983
• Tongue: English
• Weight: 639 KB
• Volume: 11
• Category: Article
• ISSN: 0344-5704
• DOI: 10.1007/bf00254194

✦ Synopsis

The development of nitrosoureas has switched from more lipophilic derivatives to congeners with higher water-solubility, since this property was presumably associated with a decrease in myelosuppression. We have compared the therapeutic efficacy of clinically well-known lipophilic nitrosoureas BCNU, CCNU, and MeCCNU with the recently introduced water-soluble nitrosoureas chlorozotocin (CZT) and hydroxyethyl-CNU (HeCNU), using a human melanoma xenograft system. There were considerable differences in tumor-inhibitory activity, with HeCNU ranking first and CZT last, and the rank order was similar for drug-induced lethality or bone marrow damage (in terms of reduced cellularity or macromolecular DNA damage). When the doses are expressed as percentages of the corresponding LD10/30 values, CZT ranks last and HeCNU low among conventional nitrosoureas. We conclude that water-solubility is not associated with reduced myelosuppression and that other guidelines will have to be adopted for rational development of nitrosoureas.