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Related Experiment Videos

Clinical studies with MTA

A H Calvert1, J M Walling

  • 1Division of Oncology, Newcastle General Hospital, Newcastle upon Tyne, UK.

British Journal of Cancer
|August 26, 1998
PubMed
Summary
This summary is machine-generated.

Multi-targeted antifolate MTA (LY231514) shows promising anti-tumour activity by inhibiting thymidylate synthase (TS). Its toxicity and efficacy are schedule-dependent, with a 3-weekly regimen chosen for further trials.

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Area of Science:

  • Pharmacology
  • Oncology
  • Drug Development

Background:

  • MTA (LY231514) is a multi-targeted antifolate that undergoes intracellular polyglutamation.
  • Polyglutamated MTA inhibits thymidylate synthase (TS) and other folate-dependent enzymes, potentially overcoming antifolate resistance.

Purpose of the Study:

  • To evaluate the anti-tumour activity and toxicity of MTA across different dosing schedules.
  • To determine the optimal dosing schedule for further clinical investigation.

Main Methods:

  • Three Phase I clinical trials were conducted using different MTA administration schedules.
  • Dose-limiting toxicities and side-effects were recorded.
  • Recommended doses were determined for each schedule.

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Main Results:

  • Toxicity was highly schedule-dependent, with the 3-weekly schedule showing a significantly higher recommended dose.
  • Neutropenia and thrombocytopenia were dose-limiting toxicities.
  • Manageable side-effects included mucositis, skin rashes, and transient transaminase elevations.

Conclusions:

  • The 3-weekly dosing schedule of MTA was selected for Phase II evaluation due to its favorable toxicity profile.
  • Preliminary Phase II results indicate encouraging anti-tumour activity in colorectal, pancreas, NSCLC, and breast cancers.