Preclinical antitumor activity of two novel taxanes

Cancer Chemother Pharmacol. 2001;47(2):97-105. doi: 10.1007/s002800000241.


Purpose: Two taxane analogs, BMS-184476 and -188797, were evaluated for their in vitro cytotoxicity and in vivo antitumor activity, and compared with paclitaxel and occasionally docetaxel (Taxotere).

Methods: Cytotoxicity was assessed in vitro using a panel of human tumor cell lines. Several different murine and human tumor models were used in vivo to evaluate the taxane analogs.

Results: Both compounds were found to have cytotoxic potency similar to paclitaxel and to partially overcome two different forms of paclitaxel resistance. BMS-184476 was found to be clearly superior to paclitaxel in three human xenograft tumor models: A2780 ovarian carcinoma; HCT/pk, a moderately paclitaxel-resistant colon carcinoma; and L2987 lung carcinoma. Additionally, in the clinically derived TAXOL-unresponsive ovarian carcinoma, HOC79, BMS-184476 performed slightly better than paclitaxel and Taxotere. BMS-184476 and paclitaxel were inactive in two murine model systems, M5076 sarcoma and the paclitaxel-resistant M109/txlr lung carcinoma. Against the parental M109 tumor, both BMS-184476 and paclitaxel performed comparably. BMS-184476 was never found to be inferior to paclitaxel. The other taxane analog, BMS-188797, displayed efficacy superior to paclitaxel in four in vivo tumor models: HOC79, HCT/ pk, M109, and L2987 carcinomas. Like paclitaxel and BMS-184476, BMS-188797 was inactive versus M5076 sarcoma.

Conclusions: Two new taxane analogs were characterized as superior to paclitaxel or Taxotere in several in vivo tumor models. Both BMS-184476 and -188797 are currently in phase I or II clinical trials.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Colonic Neoplasms / drug therapy
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Mice
  • Mice, Inbred Strains
  • Ovarian Neoplasms / drug therapy
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / therapeutic use*
  • Rats
  • Tumor Cells, Cultured


  • Antineoplastic Agents, Phytogenic
  • Paclitaxel