RESPONSE OF HUMAN TUMOR XENOGRAFTS IN ATHYMIC NUDE-MICE TO DOCETAXEL (RP-56976, TAXOTERE(R))

Docetaxel (Taxotere(R), RP 56976, NSC 628503), a new taxoid, was evalu ated for preclinical evidence of anticancer activity in athymic nude ( NCr-nu) mice bearing established, subcutaneously (s.c.) implanted huma n tumor xenografts CX-1 or KM20L2 (colon carcinomas), LX-1 (lung carci noma), MX-1 (mammary carcinoma), and SK-MEL-2 (melanoma). Other evalua tions used OVCAR-3 (ovarian carcinoma) xenografts implanted intraperit oneally (i.p.). Docetaxel was administered intravenously (i.v.) every 4 days for 3 injections (q4d x 3) except for one OVCAR-3 experiment in which the drug was given i.p. every 7 days for 3 injections. Tumor me asurements, animal body weights, and mortality were determined. The hi ghest dosage used (50 mg/kg/dose) was toxic in all experiments in whic h the 4-day treatment interval was used. The maximally tolerated dosag e (MTD) ranged from 15 to 33 mg/kg/dose. Therapeutic responses among t hese xenografts ranged from clinically important long-term tumor-free survivors (MX-1, SK-MEL-2, and OVCAR-3) to tumor growth delays of vari ous durations (CX-1, LX-1, and KM20L2). The response of SK-MEL-2, a xe nograft highly refractory to available drugs, was particularly notewor thy. These results are indicative of a broad spectrum of antitumor act ivity for docetaxel.