Epidermal growth factor receptor mutations and response to chemotherapy in patients with non-small-cell lung cancer.
BACKGROUND
The association of epidermal growth factor receptor (EGFR) mutations with the response to conventional cytotoxic chemotherapeutic agents in non-small-cell lung cancer patients has not been investigated. We retrospectively analyzed the associations between response to chemotherapy and molecular markers associated with gefitinib responsiveness including EGFR mutations.


METHODS
EGFR (exons 18, 19 and 21) and K-ras mutations (exon 2) were studied by direct sequencing and p-Erk and p-Akt expressions were studied by immunohistochemistry in archival paraffin embedded tissues. Response rate (RR) and time-to-progression (TTP) of prior chemotherapy by platinum, paclitaxel and gemcitabine were analyzed with respect to the presence of EGFR and K-ras mutations, and p-Erk and p-Akt expressions.


RESULTS
Of 90 patients investigated, 75 received platinums and 45 received paclitaxel as first-line chemotherapy agents. The RRS and TTPS of platinum- and paclitaxel-containing regimens were not affected by EGFR or K-ras mutations, nor by p-Erk or p-Akt expression. Fifty-seven patients received gemcitabine as first- or second-line chemotherapy. RR was not affected by EGFR or K-ras mutations or by p-Akt expression. However, all responders to gemcitabine exhibited (+) p-Erk expression [RR 30.6% for p-Erk (+) versus 0% for p-Erk (-), P = 0.01]. TTP was not affected by EGFR or K-ras mutations or by p-Erk or p-Akt expression.


CONCLUSIONS
EGFR mutations did not affect response to conventional chemotherapeutic agents, namely platinums, paclitaxel and gemcitabine. Our results also suggest that it may be undesirable to use gemcitabine in patients with tumors not expressing p-Erk.
Lee
Kyung-Hun
KH
Department of Internal Medicine, Seoul National University College of Medicine, Chongno-Gu, Seoul, 110-744, South Korea.
Han
Sae-Won
SW
Hwang
Pil Gyu
PG
Oh
Do-Youn
DY
Kim
Dong-Wan
DW
Chung
Doo Hyun
DH
Im
Seock-Ah
SA
Kim
Tae-You
TY
Heo
Dae Seog
DS
Bang
Yung-Jue
YJ
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D004252:DNA Mutational Analysis; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D066246:ErbB Receptors / Q000235:genetics*; D000077156:Gefitinib; D018773:Genes, erbB-1 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D017239:Paclitaxel / Q000008:administration & dosage; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D011799:Quinazolines; D003841:Deoxycytidine; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D017239:Paclitaxel; D000077156:Gefitinib; D000093542:Gemcitabine