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

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.

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.