Abstract
Pemetrexed is a multitargeted antifolate that inhibits at least three folate dependent enzymes involved in DNA synthesis. Gemcitabine is a broadly active pyrimidine nucleoside antimetabolite that is incorporated into DNA and causes chain termination. Both pemetrexed and gemcitabine, as single agents, have shown antitumor activity in a wide range of solid tumors, including non-small-cell lung cancer (NSCLC). Based on preclinical in vitro and in vivo synergism of the combination of pemetrexed and gemcitabine, the 2 drugs were studied in several phase I and II trials in patients with advanced NSCLC. The published studies found response rates between 13 to 31%, with overall survival times similar to established standard chemotherapy regimens. The grade 3 or 4 toxicities with this combination are mainly haematologic, dermatologic and transaminitis. In this paper, we review the pemetrexed-gemcitabine combination in the treatment of NSCLC patients with regards to the rationale, clinical activity as well as the future directions for this new 2-drug combination.
Keywords: Gemcitabine, NSCLC, pemetrexed
Current Drug Targets
Title: The Role of Pemetrexed Combined with Gemcitabine for Non-Small-Cell Lung Cancer
Volume: 11 Issue: 1
Author(s): Joanne Ngeow and Chee-Keong Toh
Affiliation:
Keywords: Gemcitabine, NSCLC, pemetrexed
Abstract: Pemetrexed is a multitargeted antifolate that inhibits at least three folate dependent enzymes involved in DNA synthesis. Gemcitabine is a broadly active pyrimidine nucleoside antimetabolite that is incorporated into DNA and causes chain termination. Both pemetrexed and gemcitabine, as single agents, have shown antitumor activity in a wide range of solid tumors, including non-small-cell lung cancer (NSCLC). Based on preclinical in vitro and in vivo synergism of the combination of pemetrexed and gemcitabine, the 2 drugs were studied in several phase I and II trials in patients with advanced NSCLC. The published studies found response rates between 13 to 31%, with overall survival times similar to established standard chemotherapy regimens. The grade 3 or 4 toxicities with this combination are mainly haematologic, dermatologic and transaminitis. In this paper, we review the pemetrexed-gemcitabine combination in the treatment of NSCLC patients with regards to the rationale, clinical activity as well as the future directions for this new 2-drug combination.
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Cite this article as:
Ngeow Joanne and Toh Chee-Keong, The Role of Pemetrexed Combined with Gemcitabine for Non-Small-Cell Lung Cancer, Current Drug Targets 2010; 11 (1) . https://dx.doi.org/10.2174/138945010790031081
DOI https://dx.doi.org/10.2174/138945010790031081 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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