Efficacy of camptothecin congeners in the treatment of human breast carcinoma xenografts.
We have shown recently that the plant alkaloid camptothecin and some of its derivatives inhibit growth of human breast carcinoma cells in vitro and induce complete regression of human breast tumors grown in nude mice. Because of the use of camptothecin derivatives in several clinical studies with patients bearing various types of cancer, in this report, we have investigated and described parameters and conditions that can modulate the anticancer effectiveness and cytotoxicity of these drugs when administered as suspensions. It is demonstrated that the antitumor effectiveness and drug-induced toxicity depend on the camptothecin derivative, the drug dose administered, the route of administration, and the scheduling of drug administration. 9-aminocamptothecin administered i.m. generates the best results, but for all practical purposes, 9-nitrocamptothecin administered orally appeared to be the camptothecin derivative and route of administration of choice. Further, we report the partial response of one breast tumor to camptothecin and propose that this tumor may require chemotherapy with a camptothecin derivative followed by an anticancer drug with a different mechanism of cell-killing activity.
Pantazis
P
P
Stehlin Foundation for Cancer Research, St. Joseph Hospital, Houston, Texas 77003.
Kozielski
A J
AJ
Vardeman
D M
DM
Petry
E R
ER
Giovanella
B C
BC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002166:Camptothecin