Antineoplastic Agents ; therapeutic use ; Carcinoma, Adenoid Cystic ; drug therapy ; secondary ; Erlotinib Hydrochloride ; therapeutic use ; Eye Neoplasms ; drug therapy ; secondary ; Humans ; Lacrimal Apparatus

Molecule-targeting agents inhibit the proliferation of tumor cells by the molecular biological differences between tumor cells and normal cells, and finally kill tumor cells. This article introduces several molecule-targeting agents that are currently under clinical trials now.
Angiogenesis Inhibitors ; therapeutic use ; Antibodies, Monoclonal ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Erlotinib Hydrochloride ; Humans ; Lung Neoplasms ; drug therapy ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors

OBJECTIVETo guide the optimal selection among first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in clinical practice. This review attempted to provide a thorough comparison among three first-generation EGFR-TKIs, namely icotinib, erlotinib, and gefitinib, with regard to their molecular structure, pharmacokinetic parameters, clinical data, adverse reactions, and contraindications.

DATA SOURCESAn electronic literature search of the PubMed database and Google Scholar for all the available articles regarding gefitinib, icotinib, and erlotinib in the English language from January 2005 to December 2014 was used.

STUDY SELECTIONThe search terms or keywords included but not limited to "lung cancer", "nonsmall cell lung cancer (NSCLC)", "epidemiology", "EGFR", "TKIs", and "optimal selection ".

RESULTSAs suggested by this review, even though the three first-generation EGFR-TKIs share the quinazoline structure, erlotinib had the strongest apoptosis induction activity because of its use of a different side-chain. The pharmacokinetic parameters indicated that both erlotinib and icotinib are affected by food. The therapeutic window of erlotinib is narrow, and the recommended dosage is close to the maximum tolerable dosage. Icotinib enjoys a wider therapeutic window, and its concentration in the blood is within a safe dosage range even if it is administered with food. Based on multiple large-scale clinical trials, erlotinib is universally applied as the first-line treatment. In marked contrast, icotinib is available only in China as the second- or third-line therapeutic approach for treating advanced lung cancer. In addition, it exhibits a similar efficacy but better safety profile than gefitinib.

CONCLUSIONSAlthough there is a paucity of literature regarding whether icotinib is superior to erlotinib, its superior toxicity profile, noninferior efficacy, and lower cost indicate that it is a better alternative for Chinese patients living with advanced NSCLC.

Carcinoma, Non-Small-Cell Lung ; drug therapy ; Crown Ethers ; therapeutic use ; Erlotinib Hydrochloride ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; Protein Kinase Inhibitors ; therapeutic use ; Quinazolines ; therapeutic use ; Treatment Outcome

OBJECTIVETo compare the efficacy of the erlotinib versus gefitinib in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC.

METHODSFifty patients with untreated advanced EGFR mutation- positive NSCLC were randomly divided into gefitinib group (n=27) and erlotinib group (n=23). The progression-free survival, objective response rate and disease control rate were evaluated to compare the efficacy of gefitinib and erlotinib.

RESULTSThere were no significant differences in the objective response rate (P=0.711) and disease control rate (P=0.861) between the two groups. The progression-free survival of gefitinib group and erlotinib group was 8.0 months and 10.0 months, respectively. The efficacy of the two drugs was similar (P=0.293).

CONCLUSIONThere is no significant differences between gefitinib and erlotinib in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC.

Carcinoma, Non-Small-Cell Lung ; drug therapy ; Disease-Free Survival ; Erlotinib Hydrochloride ; Humans ; Lung Neoplasms ; drug therapy ; Mutation ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; metabolism

Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; therapeutic use ; Erlotinib Hydrochloride ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Neoplasms ; drug therapy ; genetics ; metabolism ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; genetics ; metabolism ; Trastuzumab

Acrylamides ; Aniline Compounds ; Carcinoma, Non-Small-Cell Lung/genetics* ; Crizotinib/therapeutic use* ; Drug Resistance, Neoplasm/genetics* ; Erlotinib Hydrochloride/therapeutic use* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins c-met/genetics*

BACKGROUNDA retrospective analysis of clinical data were conducted reviewing patients who were given erlotinib at Peking Union Medical College (PUMC) Hospital from May 2005 to December 2009. Relationships between clinical factors, epidermal growth factor receptor (EGFR) mRNA expression, EGFR gene mutations, KRAS gene mutations and clinical outcomes were investigated in Chinese patients with advanced non-small cell lung cancer (NSCLC).

METHODSPatients with stage IIIB/IV NSCLC who had not previously participated in erlotinib related clinical trials were enrolled into this study. All patients were given oral erlotinib 150 mg per day. Tumor samples of some patients were accessed with mutant-enriched polymerase chain reaction assay (EGFR, KRAS gene mutations) and multiplex branched DNA assay (EGFR mRNA expression).

RESULTSSeventy-nine patients were enrolled in this study, 23 patients had a partial response (PR), 36 patients had a stable disease (SD), 20 patients had a PD, with an objective response rate of 29.1%, and a disease control rate of 74.7%. Females (P = 0.023), non-smokers (P = 0.013), patients with a skin rash (P = 0.047), and with highly differentiated tumors (P = 0.037) were significantly correlated with the objective response rate. Patients with a lower ECOG PS (P = 0.002), highly differentiated tumors (P = 0.014), non-smokers (P = 0.002), and patients with a skin rash (P < 0.001) were significantly correlated with the disease control rate. The median progression-free survival was 35 weeks (95%CI: 13 - 57 weeks) and 1-year survival was 72.3%. Highly-differentiated tumors (P = 0.027) and patients with a skin rash (P < 0.001) were significantly correlated with PFS. Seventeen patients were tested for EGFR/KRAS gene mutations and EGFR mRNA expression. Progression-free survival (PFS) of patients with EGFR exon 19/21 mutations was 66 weeks, longer than patients with wild type EGFR exon 19/21 (P = 0.018). No significant relationships were found between EGFR mRNA expression, EGFR exon 19/21 mutations, and KRAS mutations and objective response rate or disease control rate. The most common adverse events were skin rash (60.9%) and diarrhea (26.6%).

CONCLUSIONSErlotinib was safe and effective in treating Chinese patients with advanced NSCLC. The PFS of patients who had a skin rash, highly differentiated tumors, or EGFR exon 19/21 mutations was significantly longer.

Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Erlotinib Hydrochloride ; Female ; Humans ; Male ; Middle Aged ; Protein Kinase Inhibitors ; therapeutic use ; Quinazolines ; therapeutic use ; Retrospective Studies ; Treatment Outcome

BACKGROUNDSerum expression of cytokines may provide information about the clinical outcome of advanced non-small cell lung cancer (NSCLC) patients. This study aimed to investigate the relationship between serum cytokine levels and the clinical outcome of erlotinib treatment in a second or third line setting in patients with advanced NSCLC.

METHODSA total of 162 patients with advanced NSCLC who received erlotinib as either second or third line therapy were enrolled in this study. Blood samples were collected before the initiation of erlotinib treatment, and the levels of IL-1, IL- 2R, IL-6, and tumor necrosis factor (TNF)-α were assessed by enzyme-linked immunosorbent assay (ELISA). Cutoff points were defined as the median levels of IL-1 (low (≥26.5 pg/ml) and high (>26.5 pg/ml)), IL-2R (low ( = 115 pmol/L) and high (>15 pmol/L)), IL-6 (low (≤49.5 pg/ml) and high (>49.5 pg/ml)), and TNF-α (low (≤48.5 pg/ml) and high (>48.5 pg/ml)). Kaplan-Meier analysis was used to estimate the survival time, and Cox regression analyses were used to correlate cytokines and baseline clinical characteristics with clinical outcomes, including time to progression (TTP) and overall survival (OS).

RESULTSBetween January 2007 and May 2011, 162 patients were enrolled. Their median age was 58 years. In this group, 109 were males and 53 were females, 74 were former or current smokers and 88 were non-smokers. A total of 122 patients had adenocarcinoma, 27 had squamous cell carcinoma, and 13 had tumors with other types of histology. And 139 patients had an Eastern cooperative oncology group (ECOG) performance status of 0-1, while 23 scored at 2-3. Expression of IL-1, IL-2R, and IL-6 was not significantly associated with age, gender, ECOG performance status, smoking status, or histology and stage of tumor. Only TNF-α was associated with smoking status (P = 0.045). Survival analysis showed that patients with low levels of either IL-6 or TNF-α had a statistically longer TTP and OS than patients with high expression (P < 0.05). These cytokines remained significant upon multivariate analysis (P < 0.05).

CONCLUSIONIL-6 or TNF-α may serve as potential predictive biomarker for the efficacy of erlotinib.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; Cytokines ; blood ; Erlotinib Hydrochloride ; Female ; Humans ; Lung Neoplasms ; blood ; drug therapy ; Male ; Middle Aged ; Protein Kinase Inhibitors ; therapeutic use ; Quinazolines ; therapeutic use

BACKGROUNDSeveral clinical trials showed that erlotinib was effective after the failure of gefitinib in advanced non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the feasibility of erlotinib treatment after the failure of gefitinib based on the data from our hospital.

METHODSThe clinical data of 20 patients with advanced NSCLC who were admitted to Shanghai Chest Hospital from August 2007 to December 2008 were retrospectively analyzed. All of the patients were given erlotinib treatment after the failure of gefitinib. Survival analysis was made by Kaplan-Meier method. The Cox regression model was performed to analyze the relationship between the influential factors and the erlotinib progression-free survival (PFS).

RESULTSFive patients had a partial response (PR), nine patients had stable disease (SD) and six patients had progressive disease (PD) with gefitinib treatment. The median PFS was 277 days (95% CI 0- 566). No patient had a PR, seven had SD and fourteen PD with the erlotinib therapy. The median PFS was 31 days (95% CI 9.1- 52.9). The response rate (RR) was 0, and the disease control rate (DCR) was 35% (7/20). Cox regression analysis demonstrated that sex (P = 0.96), age (P = 0.89), smoking history (P = 0.78), performance status (PS) (P = 0.98), gefitinib efficacy (P = 0.90) and whether chemotherapy was applied between using the two drugs (P = 0.45) had no significant correlation with erlotinib PFS. Fifteen patients had epidermal growth factor receptor (EGFR) mutation status determined. There were five cases got SD with the erlotinib treatment in ten mutation negative (wild-type) patients. No SD was recorded in the five mutation positive patients.

CONCLUSIONSThe efficacy of erlotinib treatment after gefitinib failure was limited. However, the patients who are EGFR mutation negative can probably benefit from erlotinib treatment after gefitinib failure.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; mortality ; Erlotinib Hydrochloride ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Proportional Hazards Models ; Quinazolines ; therapeutic use ; Retrospective Studies ; Survival Analysis ; Treatment Outcome

Epidermal growth factor receptor (EGFR) is a major molecular for target therapy. The epidermal growth factor receptor tyrosine kinase inhibitors (TKIs), gefitinib (Iressa) and erlotinib (Tarceva), are two prospective agents towards non-small cell lung cancer (NSCLC). Multi-center clinical studies showed that there were obvious differences between individuals by the treatment of EGFR-TKIs. EGFR status is the major factor that influences the outcome for the treatment by TKI. Exon mutations and amplification of EGFR molecule are the critical factors that predict good response to TKIs. On the other hand, KRAS mutations indicate the resistant to the TKIs.
Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; Erlotinib Hydrochloride ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; Protein Kinase Inhibitors ; therapeutic use ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; genetics