Response of human tumor xenografts in athymic nude mice to docetaxel (RP 56976, Taxotere).
Docetaxel (Taxotere, RP 56976, NSC 628503), a new taxoid, was evaluated for preclinical evidence of anticancer activity in athymic nude (NCr-nu) mice bearing established, subcutaneously (s.c.) implanted human tumor xenografts CX-1 or KM20L2 (colon carcinomas), LX-1 (lung carcinoma), MX-1 (mammary carcinoma), and SK-MEL-2 (melanoma). Other evaluations used OVCAR-3 (ovarian carcinoma) xenografts implanted intraperitoneally (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 measurements, animal body weights, and mortality were determined. The highest dosage used (50 mg/kg/dose) was toxic in all experiments in which the 4-day treatment interval was used. The maximally tolerated dosage (MTD) ranged from 15 to 33 mg/kg/dose. Therapeutic responses among these xenografts ranged from clinically important long-term tumor-free survivors (MX-1, SK-MEL-2, and OVCAR-3) to tumor growth delays of various durations (CX-1, LX-1, and KM20L2). The response of SK-MEL-2, a xenograft highly refractory to available drugs, was particularly noteworthy. These results are indicative of a broad spectrum of antitumor activity for docetaxel.
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D000077143:Docetaxel; D015507:Drugs, Investigational / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology; D043823:Taxoids; D014183:Transplantation, Heterologous
D000972:Antineoplastic Agents, Phytogenic; D015507:Drugs, Investigational; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel