Therapeutic evaluation of five nitrosoureas in a human melanoma xenograft system.

Abstract

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.

• Authors: R Osieka, P Glatte, R Pannenbäcker, C G Schmidt
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 11 Issue 3 Pg. 147-52 ( 1983) ISSN: 0344-5704 [Print] Germany
• PMID: 6227420 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitrosourea Compounds
• Semustine
• chlorozotocin
• Streptozocin
• Lomustine
• elmustine
• Carmustine

Topics

• Animals
• Bone Marrow (drug effects)
• Brain Neoplasms (drug therapy)
• Carmustine (therapeutic use)
• Dose-Response Relationship, Drug
• Female
• Humans
• Lomustine (therapeutic use)
• Male
• Melanoma (drug therapy)
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Nitrosourea Compounds (therapeutic use)
• Semustine (therapeutic use)
• Streptozocin (analogs & derivatives, therapeutic use)
• Transplantation Immunology (drug effects)
• Transplantation, Heterologous