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Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice
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Preclinical pharmacology of BMS-275183, an orally active taxane

W C Rose1, B H Long, C R Fairchild

  • 1Pharmaceutical Research Institute, Bristol-Myers Squibb Co., Inc., Lawrenceville, New Jersey 08543, USA. rosew@bms.com

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 13, 2001
PubMed

Insights

Oral BMS-275183, a novel taxane, demonstrated efficacy comparable to intravenous paclitaxel across multiple tumor models. Its oral administration offers a promising alternative, with optimized dosing schedules enhancing therapeutic outcomes.

Area of Science:

  • Oncology
  • Pharmacology
  • Drug Development

Background:

  • Taxanes are a critical class of chemotherapeutic agents, primarily administered intravenously.
  • Developing orally bioavailable taxanes could improve patient compliance and treatment accessibility.
  • BMS-275183 is a novel taxane agent investigated for its anti-cancer properties.

Purpose of the Study:

  • To evaluate the anti-tumor efficacy of orally administered BMS-275183 in various preclinical cancer models.
  • To compare the effectiveness of oral BMS-275183 with intravenous paclitaxel.
  • To explore the impact of dosing schedules and combination therapy with intravenous paclitaxel.

Main Methods:

  • Preclinical efficacy studies in multiple murine and human tumor xenograft models.
  • Comparative analysis of oral BMS-275183 against intravenous paclitaxel.
  • Dose-scheduling dependency studies and combination therapy evaluations.

Main Results:

  • Oral BMS-275183 showed efficacy comparable to intravenous paclitaxel in five tumor models.
  • Activity was observed in additional colon and prostate cancer models.
  • Optimized oral dosing intervals improved tolerance and therapeutic results.
  • Combination therapy with intravenous paclitaxel demonstrated therapeutic advantages.

Conclusions:

  • Oral BMS-275183 exhibits significant anti-tumor activity across diverse preclinical models.
  • The oral route offers a viable alternative to intravenous administration for taxane therapy.
  • Further clinical investigation, including Phase I trials, is warranted for BMS-275183.

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