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Related Experiment Videos

Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors.

A R Hanauske1, V Chen, P Paoletti

  • 1Eli Lilly and Company, Indianapolis, Indiana 46285, USA. Hanauske.IND-Synergen@t-online.de

The Oncologist
|August 29, 2001
PubMed
Summary

Pemetrexed is a novel antifolate drug showing promise in various solid tumors. Dietary supplementation with folic acid and vitamin B12 is being studied to reduce its toxicities.

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Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Pemetrexed disodium (ALIMTA) is a multi-targeted antifolate with demonstrated clinical activity across numerous solid tumors.
  • It functions by inhibiting key folate-dependent enzymes crucial for purine and pyrimidine synthesis.

Purpose of the Study:

  • To evaluate the clinical activity and toxicity profile of pemetrexed.
  • To investigate the potential of dietary supplementation (folic acid and vitamin B12) to mitigate pemetrexed-induced toxicities.
  • To explore the efficacy of pemetrexed in combination therapies for various cancer types.

Main Methods:

  • Pemetrexed was administered at a dose of 500 mg/m(2) via a 10-minute infusion every 21 days.
  • Myelosuppression was identified as the dose-limiting toxicity.
  • Preclinical studies indicated that folic acid supplementation reduced toxicities while preserving antitumor activity.

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Main Results:

  • Pemetrexed demonstrated a moderate toxicity profile as a single agent.
  • Folic acid and vitamin B12 supplementation have been incorporated into ongoing clinical trials based on preclinical and clinical observations.
  • Combination studies suggest pemetrexed may be an important component of future cancer treatment regimens.

Conclusions:

  • Pemetrexed is a promising multi-targeted antifolate with broad-spectrum activity in solid tumors.
  • Dietary supplementation with folic acid and vitamin B12 is a strategy to improve the tolerability of pemetrexed therapy.
  • Further clinical trials, including Phase III studies in mesothelioma and non-small cell lung cancer, are underway to further explore the potential of this agent.