J Korean Med Assoc.  2008 May;51(5):483-491. 10.5124/jkma.2008.51.5.483.

Targeted Therapy of Lung Cancer

• Lee KY

• KMID: 2185880
• DOI: http://doi.org/10.5124/jkma.2008.51.5.483

Abstract

Atherapeutic plateau has been reached with classical cytotoxic agents in the management of advanced non-small cell lung cancer (NSCLC) patients, even though there has been some modest improvement in overall survival by platinum-based combination chemotherapy with new agents, such as gemcitabine, taxanes, and vinorelbine during the last decades. Targets of pivotal importance for the molecular pathogenesis of the lung cancer have been identified and pharmaceutical compounds against these targets have been developed. At present, we have three targeted agents which have been approved for the management of advanced NSCLC patients; two EGFR-TKIs (epidermal growth factor receptor-tyrosine kinase inhibitors), gefitinib and erlotinib, and one agent targeting angiogenesis, bevacizumab. Erlotinib monotherapy in pretreated NSCLC patients has been shown to improve overall survival compared with the placebo in BR-21 trial, while gefitinib failed to demonstrate an improvement in survival compared with placebo in ISEL study. However, gefitinib has shown therapeutic efficacy in subgroup, such as female, nonsmoker, East-Asian ethnicity, and adenocarcinoma histology. These factors are known to be predictive markers for EFGR-TKI response. EGFR mutations, especially exon 19 deletion and exon 21 L858R point mutation, are highly predictable markers for the response to EGFR-TKI, but not prognostic markers for a survival with EGFR-TKI treatment. The anti-VEGF (vascular endothelial growth factor) antibody bevacizumab has improved efficacy in the front line setting with the combination of cytotoxic chemotherapy paclitaxel/carboplatin (ECOG 4599 trial). Even though there are some excluding factors, such as squamous histology, brain metastasis, and ongoing anti-coagulation, bevacizumab in combination with paclitaxel and carboplatin is likely to be a new standard for the advanced NSCLC patients who meet the eligibility criteria in the firstline regimen. Beside these three approved agents, a large number of new targeted agents have entered the stage of clinical development. Anti-EGFR antibody cetuximab is promising in combination with cytotoxic chemotherapy. Orally available anti-VEGF-TKIs and pan-HER inhibitors may be the next generation.

Keyword

Targeted agents; NSCLC; Gefitinib; Erlotinib; Bevacizumab

MeSH Terms

Adenocarcinoma
Antibodies, Monoclonal, Humanized
Bevacizumab
Brain
Carboplatin
Carcinoma, Non-Small-Cell Lung
Cetuximab
Cytotoxins
Deoxycytidine
Drug Therapy, Combination
Erlotinib Hydrochloride
Exons
Female
Humans
Lung
Lung Neoplasms
Neoplasm Metastasis
Paclitaxel
Phosphotransferases
Point Mutation
Quinazolines
Taxoids
Vinblastine
Antibodies, Monoclonal, Humanized
Carboplatin
Cytotoxins
Deoxycytidine
Paclitaxel
Phosphotransferases
Quinazolines
Taxoids
Vinblastine

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