ANTITUMOR-ACTIVITY OF TAXOL (NSC-125973) IN HUMAN OVARIAN CARCINOMAS GROWING IN THE PERITONEAL-CAVITY OF NUDE-MICE

Background: The unique mechanism of action of taxol (NSC-125973) as microtubule stabilizing agent and its potential activity in clinical trials have generated considerable interest in the development of this agent. As taxol was reported to be active on advanced and refractory ovarian carcinomas we focused our studies on the xenograft model of human ovarian carcinoma that develops ascites and tumor dissemination in the peritoneal cavity of nude mice. Methods: The antitumor activity of taxol was evaluated on two human ovarian carcinoma xenografts (HOC8 and HOC22) transplanted i.p. in nude mice. Drug was given i.v. at doses of 20-34.5 mg/kg every four days three times (Q4 x 3) and the increment of life span (%ILS) was evaluated. Cisplatin at the dosage of 4mg/kg, Q4 x 3 was used as reference drug in each experiment. Results: Taxol given at doses of 20 mg/kg and 34.5 mg/kg to early-stage HOC22 (treatment starting 3 days after tumor transplant) cured all the mice, while the same dose regimens given to advanced HOC22 (treatment starting 14 days after tumor transplant) significantly prolonged the survival time of the mice (ILS = 197% and 300%). Taxol given 3 days after HOC8 transplant significantly prolonged the survival time of tumor-bearing nude mice, inducing complete responses in 50% and 25% of mice receiving, respectively, 34.5 mg/kg/injection and 20 mg/kg/injection. On both ovarian carcinoma xenografts taxol was more active than equitoxic doses of the reference drug cisplatin. Conclusions: The therapeutic activity against ovarian carcinoma xenografts supports the potential of taxol in the treatment of this neoplasia and forms the basis for future investigations aimed at optimizing the therapeutic activity of taxol given alone or in combination with other drugs.