Response of human tumor xenografts in athymic nude mice to docetaxel (RP 56976, Taxotere)

Invest New Drugs. 1995;13(1):1-11. doi: 10.1007/BF02614214.

Abstract

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.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / pathology
  • Docetaxel
  • Drugs, Investigational / pharmacology*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / pathology
  • Melanoma / drug therapy
  • Melanoma / pathology
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / pathology
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / pharmacology
  • Taxoids*
  • Transplantation, Heterologous

Substances

  • Antineoplastic Agents, Phytogenic
  • Drugs, Investigational
  • Taxoids
  • Docetaxel
  • Paclitaxel