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Pemetrexed for treatment of advanced non-small cell lung cancer
1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
The novel antifolate pemetrexed targets multiple enzymes involved in folate metabolism, resulting in inhibition of DNA synthesis. Pemetrexed has shown antitumor activity in preclinical models against a variety of tumor types, including non-small cell lung cancer. Phase II studies have confirmed its single-agent activity and manageable toxicity profile, and pemetrexed has shown antitumor activity in combination with other chemotherapeutics, including gemcitabine, taxanes, platinums, and vinorelbine, in the first-line treatment of advanced non-small cell lung cancer. A large ongoing phase III trial is comparing the activity of pemetrexed versus docetaxel in the second-line setting. Supplementation with oral folic acid and vitamin B12 was shown to reduce pemetrexed-related toxicity and increase its therapeutic index. These data suggest that pemetrexed has significant activity in advanced non-small cell lung cancer and represents a new treatment option for patients with this disease.
Insights
Pemetrexed, an antifolate drug, shows significant antitumor activity in advanced non-small cell lung cancer. Supplementation with folic acid and vitamin B12 improves its safety and efficacy, offering a new treatment option.
Area of Science:
- Oncology
- Pharmacology
Background:
- Pemetrexed is a novel antifolate drug inhibiting DNA synthesis by targeting folate metabolism enzymes.
- It exhibits antitumor activity in preclinical models for various cancers, including non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To evaluate the efficacy and safety of pemetrexed in advanced non-small cell lung cancer.
- To explore pemetrexed's role as a single agent and in combination therapies.
- To assess the impact of folic acid and vitamin B12 supplementation on pemetrexed's therapeutic index.
Main Methods:
- Review of preclinical data and Phase II clinical studies on pemetrexed in NSCLC.
- Analysis of combination therapy trials with gemcitabine, taxanes, platinums, and vinorelbine.
- Consideration of ongoing Phase III trials comparing pemetrexed with docetaxel.
Main Results:
- Pemetrexed demonstrates significant single-agent antitumor activity in advanced NSCLC.
- Combination therapies with pemetrexed show efficacy in first-line treatment.
- Folic acid and vitamin B12 supplementation reduce pemetrexed toxicity and enhance its therapeutic index.
Conclusions:
- Pemetrexed is an active agent in advanced non-small cell lung cancer.
- It represents a valuable new treatment option for patients with this disease.
- Supplementation strategies can optimize pemetrexed's clinical utility.
