Phase I trials of pemetrexed

Area of Science:

• Oncology
• Pharmacology

Background:

• Pemetrexed is a multitargeted antifolate drug used in cancer therapy.
• Its maximum tolerated dose is 600 mg/m(2) every 3 weeks without folic acid supplementation.
• Folic acid and vitamin B12 supplementation may allow for higher pemetrexed doses with reduced toxicity.

Purpose of the Study:

• To evaluate the safety and efficacy of pemetrexed, both as a single agent and in combination therapies.
• To identify dose-limiting toxicities and adverse effects of pemetrexed.
• To explore the potential of pemetrexed in various cancer types.

Main Methods:

• Phase I clinical trials were conducted to assess pemetrexed.
• Dose escalation studies were performed with and without folic acid and vitamin B12 supplementation.
• Combinations of pemetrexed with other chemotherapeutic agents and radiotherapy were investigated.

Main Results:

• Dose-limiting toxicities include neutropenia, asthenia, and thrombocytopenia.
• Pemetrexed can be safely administered at doses of 400-600 mg/m(2) in combination with various chemotherapy agents.
• Preliminary data suggest safety with doses of 400-500 mg/m(2) in combination with taxanes and vinorelbine.
• Pemetrexed demonstrated activity in colorectal, pancreatic, breast, non-small cell lung cancers, and mesothelioma.

Conclusions:

• Pemetrexed is an active agent against a wide spectrum of tumors.
• Its adverse effects are manageable and potentially reduced with folic acid and vitamin B12 supplementation.
• Pemetrexed shows promise as a single agent and in combination therapies for various cancers.