BACKGROUND AND OBJECTIVEEpidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has been widely used as the second- and third-line therapy in patients with advanced non-small cell lung cancer (NSCLC). However, its effect in the first-line treatment is unclear. The aim of this study was to evaluate the efficacy and safety of EGFR-TKI as first-line therapy.

METHODSThe clinical characteristics, responses rate, disease control rate and overall survival were retrospectively analyzed in 77 chemonaive patients with advanced NSCLC. All of the patients received oral gefitinib (250 mg/d) or erlotinib (150 mg/d) until disease progression or unacceptable toxicity occurrence.

RESULTSThe overall response rate was 33.8% and the disease control rate was 68.8%. The median progression-free survival and the median survival time were 6.0 months and 8.9 months, respectively. One-year survival rate was 61.4%. Responses correlated significantly with histology, PS score, smoking history, skin rash, EGFR mutations and serum CEA. Histology and skin rash were the independent predictors of survival. Common toxicities were skin rash and mild diarrhea. EGFR-TKI could improve the clinical symptoms and the quality of life.

CONCLUSIONEGFR-TKI is effective and well tolerated as first-line therapy in patients with advanced NSCLC.

Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; mortality ; Erlotinib Hydrochloride ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Quinazolines ; administration & dosage ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Retrospective Studies ; Young Adult

One group of Bcl-2 protein family, which shares only the BH3 domain (BH3-only), is critically involved in the regulation of programmed cell death. Herein we demonstrated a novel human BH3-only protein (designated as Bop) which could induce apoptosis in a BH3 domain-dependent manner. Further analysis indicated that Bop mainly localized to mitochondria and used its BH3 domain to contact the loop regions of voltage dependent anion channel 1 (VDAC1) in the outer mitochondrial membrane. In addition, purified Bop protein induced the loss of mitochondrial transmembrane potential (Δψm) and the release of cytochrome c. Furthermore, Bop used its BH3 domain to contact pro-survival Bcl-2 family members (Bcl-2, Bcl-X(L), Mcl-1, A1 and Bcl-w), which could inhibit Bop-induced apoptosis. Bop would be constrained by pro-survival Bcl-2 proteins in resting cells, because Bop became released from phosphorylated Bcl-2 induced by microtubule-interfering agent like vincristine (VCR). Indeed, knockdown experiments indicated that Bop was partially required for VCR induced cell death. Finally, Bop might need to function through Bak and Bax, likely by releasing Bak from Bcl-X(L) sequestration. In conclusion, Bop may be a novel BH3-only factor that can engage with the regulatory network of Bcl-2 family members to process intrinsic apoptotic signaling.
Amino Acid Sequence ; Animals ; Apoptosis ; Cell Line ; Cell Survival ; Humans ; Mice ; Mitochondria ; metabolism ; Mitochondrial Membranes ; metabolism ; Molecular Sequence Data ; Protein Structure, Tertiary ; Protein Transport ; Proto-Oncogene Proteins c-bcl-2 ; chemistry ; metabolism ; Signal Transduction ; Time Factors ; Voltage-Dependent Anion Channel 1 ; metabolism ; bcl-2 Homologous Antagonist-Killer Protein ; metabolism ; bcl-2-Associated X Protein ; metabolism