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Published on: February 12, 2017
An evaluation of pemetrexed in second-line treatment of non-small cell lung cancer
1Department of Clinical & Biological Sciences Head, Luigi Hospital-Regione Gonzole 10, University of Torino, 10043 Orbassano, Turin, Italy. scagliotti@ihnet.it
Abstract:
Pemetrexed is a novel antifolate antimetabolite that targets multiple folate-dependent enzymatic pathways and inhibits multiple enzymes involved in purine and pyrimidine synthesis. Its targets include pathways that, when amplified, are associated with reduced efficacy in conventional cytotoxic agents. As second-line treatment for advanced non-small cell lung cancer, (NSCLC) pemetrexed, when administered with folic acid and vitamin B12, has demonstrated comparable efficacy and a superior toxicity profile relative to docetaxel. A retrospective analysis of the Phase III trial of pemetrexed versus docetaxel shows a statistically significant longer toxicity-free survival time for pemetrexed compared with docetaxel. Newer targeted therapies, especially the epidermal growth factor receptor inhibitors gefitinib and erlotinib, have produced conflicting results and have only been compared with best supportive care and placebo. They should be compared directly to pemetrexed as second-line therapy in large, randomised studies of patients with advanced NSCLC. For patients with advanced recurrent NSCLC and good performance status who progress after first-line chemotherapy, pemetrexed should be considered as a new standard of care.
Insights
Pemetrexed offers comparable efficacy to docetaxel for advanced non-small cell lung cancer (NSCLC) with a better safety profile. It provides longer toxicity-free survival, making it a potential new standard of care.
Area of Science:
- Oncology
- Pharmacology
Background:
- Pemetrexed is a novel antifolate antimetabolite targeting key enzymes in purine and pyrimidine synthesis.
- Amplified folate-dependent pathways can reduce the efficacy of conventional cytotoxic agents in non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To evaluate pemetrexed as a second-line treatment for advanced non-small cell lung cancer (NSCLC).
- To compare the efficacy and toxicity profile of pemetrexed with docetaxel in advanced NSCLC.
Main Methods:
- Retrospective analysis of a Phase III trial comparing pemetrexed with docetaxel in advanced NSCLC patients.
- Evaluation of pemetrexed administered with folic acid and vitamin B12.
Main Results:
- Pemetrexed demonstrated comparable efficacy to docetaxel.
- Pemetrexed showed a superior toxicity profile and a statistically significant longer toxicity-free survival time compared to docetaxel.
- Newer targeted therapies like EGFR inhibitors have shown conflicting results and require direct comparison with pemetrexed.
Conclusions:
- Pemetrexed should be considered a new standard of care for advanced recurrent NSCLC patients with good performance status who progress after first-line chemotherapy.
- Further large, randomized studies are needed to directly compare pemetrexed with newer targeted therapies in advanced NSCLC.