Antitumor activity of taxotere (RP 56976, NSC 628503), a new taxol analog, in experimental ovarian cancer.
BACKGROUND
The new cytostatic agent taxol has clearly demonstrated its effectiveness in ovarian cancer patients. The synthesis of drugs related to taxol could overcome its limited natural supply and may have additional benefits, such as greater efficacy or better solubility. Taxotere (RP 56976, NSC 628503) is such a compound. We investigated the drug for its antitumor activity in human ovarian cancer xenografts.


METHODS
Five human ovarian cancer lines were selected with respect to differences in histological sub-types, growth rates and chemosensitivity to conventional cytostatic agents. Tumors were implanted as fragments s.c. into both flanks of female nude mice (Hsd: athymic nude-nu). Treatment was started in groups of 5-8 mice at the time mean tumor volume measured 50-150 mm3. Taxotere was injected i.v. weekly x 2. Drug efficacy was expressed as the maximum percentage of growth inhibition of treated tumors as compared to control tumors.


RESULTS
At the maximum tolerated dose of 15-20 mg/kg for weekly i.v. x 2 injections, taxotere induced a mean weight loss of 10%-15% of the initial weight within 2 weeks after the first injection. The maximum percentage of growth inhibition obtained was > or = 50% in 4/5 lines and > or = 90% in 3/5 lines. In 2 lines, taxotere appeared more effective than cisplatin, cyclophosphamide or doxorubicin, drugs studied previously at maximum tolerated doses in the same tumor lines.


CONCLUSIONS
Our findings in human ovarian cancer xenografts hold promise for the efficacy of taxotere in this type of disease in the clinic.
Boven
E
E
Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
Venema-Gaberscek
E
E
Erkelens
C A
CA
Bissery
M C
MC
Pinedo
H M
HM
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D000077143:Docetaxel; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000627:therapeutic use; D043823:Taxoids; D014183:Transplantation, Heterologous
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D002945:Cisplatin