The role of pemetrexed combined with gemcitabine for non-small-cell lung cancer.
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.
Department of Medical Oncology, National Cancer Centre, Singapore.
Joanne
J
Ngeow
Chee-Keong
CK
Toh
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005971:Glutamates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D000068437:Pemetrexed; D000093542:Gemcitabine
D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000093542:Gemcitabine