Analysis of the Reports of Adverse Dug Reaction Induced by EGFR-TKI in Shandong Province / 中国药房

OBJECTIVE：To analyze the clinical manifestations and characteristics of adverse drug reactions （ADR）induced by EGFR-TKI，and to provide reference for safe use of drugs in clinic. METHODS ：The relevant data of EGFR-TKI-induced ADR reports which were reported to Shandong ADR Monitoring Center from January 2018 to December 2020 were summarized ，and analyzed statistically in respects of age ，gender，drug variety ，ADR classification ，usage and dosage ，occurrence time ，involved organs/systems，clinical manifestations and prognosis of patients. RESULTS & CONCLUSIONS ：A total of 120 ADR reports induced by EGFR-TKI were included ，involving 120 patients. Among 120 patients，the female （60.83％）was more than the male （39.17％），and the age was mainly 50-79 years old （79.16％）. A total of 5 drugs including gefitinib ，ositinib，afatinib，ektinib and erlotinib were involved. ADR occurred in 72，11，15，6 and 16 patients using the above drugs respectively ；the main ADR was general ADR （70.83％），followed by severe ADR （22.50％），new general ADR （5.00％）and new severe ADR （1.67％）. All patients were given drugs orally ，off-label use was found in 2 patients who used ektinib ，and the rest met the medication requirements of the drug instructions. ADR occurred in 61 patients（50.83％）within 1 month after medication ，34 patients （28.33％）within 1-3 months after medication ，25 patients（20.83％）within 4-12 months after medication ，and no ADR occurred after 12 months. ADR of organs/systems involved were mainly the lesion of skin and its appendant injury，gastrointestinal system injury and hepatobiliary system injury. The main clinical manifestations were rash ，diarrhea and abnormal liver function ；in addition，some patients developed severe or new severe ADR such as interstitial pneumonia ，bone marrow suppression ，tongue swelling and cerebral infarction. Totally 102 patients recovered or improved after drug withdrawal or symptomatic treatment ，12 patients had unknown outcome ，and 6 patients did not improve. It is suggested that pharmaceutical care should be strengthened within 1 month after EGFR-TKI administration ，so as to guard against the occurrence of new and serve ADR and ensure the safety of clinical medication.

Efficacy and safety of bevacizumab combined with first-generation egfr-tki in the first-line treatment of egfr-mutated advanced non-small cell lung cancer: A meta-analysis / 肿瘤

Objective: To evaluate the efficacy and safety of Bevacizumab (BEV) combined with first-generation EGFR-TKI versus first-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) alone in the first-line treatment of EGFR-mutated positive (EGFRm) advanced non-small cell lung cancer(NSCLC). Methods: PubMed, Cochrane Library, Embase, Weipu chinese journal, China Biology Medicine database, China National Knowledge Infrastructure and Wanfang relevant databases were searched to collect randomized controlled trials (RCTs) of BEV combined with first-generation EGFR-TKI (experimental group) versus first-generation EGFR-TKI alone (control group) in the first-line treatment of EGFRm advanced NSCLC from database foundation to July, 2019. The data in the included RCTs were extracted, and the qualities were assessed in accordance with Cochrane Collaboration, and a Meta-analysis was conducted with RevMan 5.3 software, Risk ratio (RR), hazard ratio (HR) and 95% confidence interval (CI) were calculated. Results: A total of 7 RCTs were enrolled, including 834 patients. The results of meta-analysis showed that experimental group was better than control group in objective response rate (ORR) (RR = 1.27, 95% CI: 1.15-1.41, P < 0.000 01), disease control rate (DCR) (RR = 1.10, 95% CI: 1.02-1.20, P = 0.02) and progression-free survival (PFS) (HR = 0.57, 95% CI: 0.44-0.75, P < 0.000 1) in terms of efficacy. In terms of safety, the incidences of hypertension (RR = 4.11, 95% CI: 2.95-5.93, P < 0.000 01], proteinuria (RR = 5.16, 95% CI: 3.40-7.83, P < 0.000 01), hemorrhage (RR = 3.34, 95% CI: 2.37-4.72, P<0.000 01) were higher in experimental group. There was no significant difference between the two groups in the incidences of rash (RR = 1.00, 95% CI: 0.92-1.08, P = 0.91), diarrhea (RR=1.05, 95% CI: 0.91-1.21, P = 0.52), hypohepatia (RR = 0.91, 95% CI: 0.72-1.14, P = 0.42). Conclusion: BEV combined with first-generation EGFR-TKI significantly improve ORR, DCR and PFS in the first-line treatment of EGFRm advanced NSCLC, but also increase the risks of hypertension, proteinuria and hemorrhage.

Acquired Drug Resistance Mechanism of Osimertinib in the Targeted Therapy of Non-small Cell Lung Cancer / 中国肺癌杂志

While treating cancer, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) still faces inevitable drug resistance. Investigations into the mechanisms which foster resistance to EGFR-TKI has led to the discovery of novel biomarkers and drug targets, and in turn has enabled the development of third-generation TKIs and proposals for rational therapeutic combinations. The threonine-to-methionine substitution mutation at position 790 (T790M) is clinically validated to engender refractoriness to first- and second-generation TKI, and is a standard-of-care predictive biomarker used in therapeutic stratification. For patients who are T790M-negative, cytotoxic chemotherapy or protracted EGFR-TKI treatment are acceptable treatment standards after disease progression, although combinations of targeted therapies and checkpoint blockade immunotherapy may offer promising alternatives in the future. Among T790M-positive patients, the third-generation EGFR-TKI, osimertinib, has shown superiority over both platinum-doublet chemotherapy and first-generation EGFR-TKI in randomized clinical trials. This article appraises the key literature on the contemporary management of non-small cell lung cancer patients with acquired resistance to EGFR-TKIs, and envisions future directions in translational and clinical research.

Molecular Mechanism and Progression of Primary Resistance to EGFR-TKI - Analysis of 2 Cases / 中国肺癌杂志

Tyrosine kinase inhibitor (TKI) have been proved to be effective in the treatment of advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) sensitive mutation, which is superior to chemotherapy. However, there are still some patients with sensitive mutations have primary drug resistance. It may be related to the coexistence of susceptible and resistant mutations of EGFR gene, downstream mutations of EGFR pathway, MET amplification and BIM deletion polymorphism. We present 2 cases of primary drug resistance and analyze the reasons.
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EGFR-TKI ADR Management Chinese Expert Consensus / 中国肺癌杂志

ErbB receptor tyrosine kinase inhibitors (EGFR-TKI), gefitinib, erlotinib, icotinib and aftinib, which are approved as a frontline treatment for patients with non-small cell lung cancer (NSCLC) who have tumors harboring EGFR mutations in China. And osimertinib was approved in second line setting for patients with EGFRT 790M-positive NSCLC. Rash, paronychia, diarrhea, stomatitis, liver dysfunction and (interstitial lung disease, ILD) are frequently observed in patients treated with EGFR-TKI. Chinese Society of Lung Cancer, Chinese Anti-Cancer Association, organized Chinese experts to develop the Chinese expert consensus on EGFR-TKI adverse event (AE) management based on domestic diagnosis and treatment of ADR and also incorporating international updated theory and recommendations.
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Prognostic Analysis of EGFR-TKIs Combined with Gamma Knife in EGFR-mutant Lung Adenocarcinoma with Brain Metastasis / 中国肺癌杂志

BACKGROUND@#Advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma had a high overall incidence of brain metastasis during the full course, and local brain radiotherapy combined with systemic targeted therapy may be a better strategy. This study aimed to identify the prognostic factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients who received EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in combination with gamma knife radiosurgery.@*METHODS@#Retrospective analysis of EGFR-mutant lung adenocarcinoma patients with brain metastases which developed at initial diagnosis or during EGFR-TKIs treatment period were performed. Intracranial progression free survival (PFS) was statistically analyzed between different subgroups to find out the prognostic factors including gender, age, smoking history, extracranial metastasis, EGFR mutation type, size and number of intracranial lesions, carcino-embryonic antigen (CEA) level, lung-molGPA score and so on.@*RESULTS@#A total of 74 EGFR-mutant brain-metastatic lung adenocarcinoma patients were enrolled in this study, with median intracranial PFS of 14.7 months. One-year intracranial-progression-free rate was 58.5%, and two-year rate was 22.2%. Univariate survival analysis showed that patients with lower CEA level at initial diagnosis (3)(15 months vs 12.6 months, P=0.041) were prone to have a superior intracranial PFS. Multivariate analysis showed that CEA≥10 ng/mL and intracranial lesion≥2 cm were the independent risk factors of intracranial PFS.@*CONCLUSIONS@#EGFR-TKIs in combination with gamma knife radiosurgery was an efficient treatment option to control the cranial tumor lesion. CEA≥10 μg/L at initial diagnosis and intracranial lesion≥2 cm were the risk factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients receiving EGFR-TKIs in combination with gamma knife radiosurgery.

Analysis of Epidermal Growth Factor Receptor Gene Mutation in 274 Cases of Non-Small Cell Lung Cancer / 中国药房

OBJECTIVE:To study the gene mutation status of epidermal growth factor receptor(EGFR)in non-small cell lung cancer(NSCLC)patients and its relationship with clinical indexes,and to provide reference for individualized administration of EGFR-TKI in NSCLC patients. METHODS:Totally of 274 NSCLC patients from the northern of Jiangsu area were selected from our hospital during Jan. 2015-Dec. 2017. Mutation status of EGFR gene in lung tissue was determined by amplification refractory mutation system (ARMS)-TaqMan PCR assay. The relationship of EGFR gene mutation with clinical indexes as gender,age, smoking status, staging, tumor differentiation and pathological type were analyzed retrospectively. Compared with related literatures,the regional differences of EGFR gene mutation were analyzed. RESULTS:Among 274 NSCLC patients,112 patients suffered from EGFR gene mutation with total mutation rate of 40.88%. There were 50,57,3,2 cases of exon 19,exon 21,exon 20 and exon 19+21 mutation,and the types of EGFR gene mutation were delE746-A750,L858R and insH773-V774H,etc. The mutation rates of EGFR gene exon 19,exon 21 in non-smoking,early,well-differentiated and adenocarcinoma patients were 52.50%,47.24%,46.36% and 45.00%,which were significantly higher than smoking (28.57%),advanced (27.03%), poor-differentiated(31.71%)and squamous cell carcinoma(27.66%)patients,with statistical significance(P＜0.05). There was no statistical significance in mutation rates of EGFR gene exon 19 and exon 21 between male and female,≥65 year-old and ＜65 year-old patients (P＞0.05). EGFR mutation rate of NSCLC subjects from the northern of Jiangsu area was significantly higher than Shanghai area(P＜0.05);there was no statistical significance compared with Yunnan area(P＞0.05)but mutation types were different. CONCLUSIONS:There is the highest EGFR gene mutation rate in its exon 21,lesser in exon 19,rare in exon 20 and exon 19+21 among NSCLC patients from the Northern of Jiangsu area. There are obvious regional differences. The mutation rate of EGFR gene mutation exon 19 and exon 21 are associated with smoking status,staging,tumor differentiation and pathological type of NSCLC patients. The non-smoking, early stage, well-differentiated and adenocarcinoma patients are more likely to benefit from EGFR-TKI targeted therapy.

Pulmonary toxicity related to EGFR-TKI monotherapy or its combination with radia-tion as treatment for non-small cell lung cancer / 中国肿瘤临床

Monotherapy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) serves as the first-line treatment for non-small cell lung cancer (NSCLC) patients with EGFR mutation. Pre-clinical studies confirmed that TKIs can increase radiation sensitiv-ity. Clinical studies confirmed that EGFR-TKI combined with radiotherapy may improve survival of patients and can be used as alterna-tive to chemoradiotherapy. Pulmonary toxicity induced by EGFR-TKIs monotherapy features low incidence rate but high mortality rate, and the incidence rate raries when TKIs is combined with radiotherapy. In this review, we summarise related literature on pulmonary toxicity in EGFR-TKI monotherapy or its combination with radiotherapy for advanced NSCLC. This study can serve as reference for safe-ty of this combined therapy.

Association between EGFR mutation status and efficacy of first-line EGFR-TKI in patients with ;advanced non-small cell lung cancer / 国际肿瘤学杂志

Objective To evaluated the effect of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)on advanced non-small cell lung cancer (NSCLC)patients with different EGFR mutation status (exon 1 9 deletion and exon 21 mutation).Methods Seventy-two advanced NSCLC patients with EGFR mutation confirmed by histopathology were enrolled.All of the patients received first-line EGFR-TKI.The relationships between EGFR mutation status and objective response rate (ORR),disease control rate (DCR),progression free survival (PFS ) and overall survival (OS ) were analyzed.Results Of the 72 patients,37 patients expressed exon 1 9 deletion,35 patients expressed exon 21 mutation,and all of them could be evaluated.The ORR and DCR of patients with exon 1 9 deletion were higher than those of patients with exon 21 mutation (75.7%vs.51 .4%,χ2 =4.583,P=0.032;89.2%vs.68.6%,χ2 =4.636,P=0.031 ).The modified median PFS of patients with exon 1 9 deletion was significantly higher than that of patients with exon 21 mutation (1 3.2 month vs.1 0.8 month,χ2 =4.700,P=0.030).The median OS of patients with exon 1 9 deletion was significantly higher than that of patients with exon 21 mutation (30.2 month vs.25.6 month,χ2 =4.686,P=0.030).The side effects were similar between the two groups.The most common adverse reaction was rash,and the incidence had no significant difference between the two groups (48.7% vs.48.6%,χ2 =0.000,P=0.995 ).Conclusion EGFR mutation status is a predictor for PFS,OS and ORR of first-line EGFR-TKI in patients with advanced NSCLC.NSCLC patients with EGFR exon 1 9 deletion are associated with longer survival time and better response rate compared with those with exon 21 mutation.

Meta-analysis on effectiveness and safety of traditional Chinese medicine combined with first-generation EGFR-TKI in treating advanced non-small cell lung cancer / 中国中药杂志

To evaluate the efficacy and safety of traditional Chinese medicine combined with first-generation EGFR-TKI in treating advanced non-small cell lung cancer (NSCLC). China biomedical literature database (CBM), China Journal Full-text Database (CNKI), VIP, PubMed, CochraneLibrary, EMbase and other Chinese and English databases were searched for randomized and clinical controlled trials of traditional Chinese medicine combined with first-generation EGFR-TKI in treating advanced NSCLC. The statistical effect was measured by Revman 5.3.5 based on the outcome indexes of total response rate, disease control rate, quality of life, one-year survival rate, and adverse reactions/events. Meanwhile, a bias risk assessment was conducted by Stata12.0. A total of 17 studies were included, involving 1 391 cases, with 706 cases in the treatment group and 685 cases in the control group. The studies featured a low methodological quality, high homogeneity and low publication bias risk. The meta-analysis showed that total response rate [RR=1.33, 95%CI (1.17, 1.51)], disease control rate [RR=1.21, 95%CI (1.13, 1.29)], quality of life improvement rate [RR=1.28, 95%CI (1.17, 1.41)], one-year survival rate [RR=1.27, 95%CI (1.01, 1.61)], and other indexes of effectiveness of Chinese medicine combined with first-generation EGFR-TKI were all superior to those of first-generation EGFR-TKI alone, with significant differences (P<0.05). Meanwhile, the incidence of adverse reaction/events, such as the skin toxic response [RR=0.74，95%CI (0.63, 0.86)], gastrointestinal reaction [RR=0.54，95%CI (0.41, 0.71)], damage to hepatic function [RR=0.41, 95%CI (0.26, 0.67)] in Chinese medicine combined with first-generation EGFR-TKI group were lower than those in first-generation EGFR-TKI group, with significant differences (P<0.01). There was no publication bias according to Begg Rank correlation test. In short, traditional Chinese medicine combined with first-generation EGFR-TKI had a better efficacy and safety in treating advanced NSCLC than EGFR-TKI alone. However, due to the small sample size and the low methodological quality of included papers, the conclusion still needs to be further proved by high-quality, large-sample randomized controlled trials.

Research Progress in Ameliorating EGFR-TKIs Acquired Resistance of Targeted Therapy in Lung Cancer by Traditional Chinese Medicine / 中国中医药信息杂志

Acquired resistance of EGFR-TKIs has become the major limitation of the efficacy of targeted therapy for lung cancer. Lung cancer has been treated by traditional Chinese medicine (TCM) combined with EGFR-TKIs, which originated from clinic. In recent years, reversing research has been conducted based on clinic application to discuss TCM intervening, improving and reversing EGFR-TKIs acquired resistance becoming a novel target for research. This article reviewed mechanism and effects of TCM herbs and compounds’ with the efficacy of clearing away heat and toxic materials, promoting blood circulation to remove blood stasis strengthening the body resistance, and invigorating the circulation of blood, and proposed that the whole regulation and targeted therapy of TCM may carry out synergistic effect and become innovation treatment model for lung cancer.

Advances in radiotherapy combined with EGFR-TKIs for non-small cell lung cancer / 中国肿瘤临床

Lung cancer is the main cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) accounts for about 80% of lung cancer cases, but only 25%-30% of initially diagnosed patients have the option of radical surgery because of the lack of effective measures for early diagnosis. For locally advanced and advanced NSCLC, radiotherapy alone or comprehensive treatment with chemoradiotherapy is the main treatment method; however, the curative effect is unsatisfactory. Recently, increasing evidence sug-gests that targeted drugs, such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), combined with radiotherapy/chemoradiotherapy represent a promising treatment modality for NSCLC. This review will discuss the research status of EGFR-TKIs and radiotherapy for locally advanced and advanced NSCLC.

Research progress of Hedgehog-Gli signaling pathway in lung cancer / 实用肿瘤学杂志

Hedgehog-Gli signaling pathway involves in vertebrate embryonic development ,tissue differ-entiation,organogenesis,and plays an important role in homeostasis ,the maintenance of stem cell function ,regula-tion of epithelial mesenchymal transition .Hedgehog-Gli signaling pathway activation correlates with a variety of tumor development ,invasion,apoptosis and drug resistance .This review seeks to clarify the composition of Hedge-hog-Gli signaling pathway ,mechanism of action ,the role of Hedgehog-Gli signaling pathway in lung cancer de-velopment and function of lung cell of the EGFR -TKI resistance .

Mechanism and strategy of the secondary resistance to EGFR-TKI in patients with lung cancer / 国际肿瘤学杂志

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is one of the most important targeted drugs for lung cancer patients carrying EGFR sensitive mutations.However,almost all patients that are effective to this treatment will eventually develop secondary resistance to EGFR-TKI.The most accepted mechanisms of resistance mainly include T790M mutation,MET amplification,PIK3CA mutation,down-regulation of PTEN expression and activation of Fas-transcription factor-κB.Recent years,many new drugs are developed to overcome this resistance.Although most of drugs are in the stages of cell or animal experiment,some new drugs get positive clinical results.

Clinical value of serum COX-2 in predicting patients′ responses to targeted therapy for advanced NSCLC / 实用医学杂志

Objective To explore the clinical value of expression levels of serum COX-2 in patients with advanced NSCLC before and after EGFR-TKI treatment. Methods The serum was collected from 58 cases. Before and after targeted therapy , the serum COX-2 level was examined by ELISA. Meanwhile , CT scan was exercised to evaluate the treatment. Follow-up interview was done. The relationship among the change in expression level of serum COX-2 , efficacy and PFS was analyzed. Results The serum COX-2 level significantly decreased in the response group (t = 11.258, P = 0.000) and increased in the PD group (t = -7.759, P =0.000) after EGFR-TKI treatment, and not significantly changed in the SD group (t = 1.424, P = 0.170). Before treatment, the baseline serum COX-2 level in the response group was significantly higher than that in the SD group and the PD group (F = 20.852, P = 0.000 ). Before the targeted therapy, the higher the level of serum COX-2 was, the longer PFS patients would enjoy. Conclusion Detection of the serum COX-2 contributes to the judgment of therapeutic effect of EGFR-TKI and can be used as a prediction of EGFR-TKI drugs outcomes for patients with advanced NSCLC.

Research progress of radiotherapy combined with EGFR-TKI in the treatment of brain metastasis from lung cancer / 肿瘤研究与临床

Brain metastasis is a common and devastating consequence of disease progression in patients with lung cancer.Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) may enhance radiosensitivity by reducing the cells in S phase,reducing angiogenesis of tumor cells,increasing irradiation apoptosis,inhibiting tumor cells proliferation by fractionated irradiation and reducing radiotherapy resistance.The clinical results of radiotherapy combined with EGFR-TKI (such as gefitinib) in treatment of brain metastasis from lung cancer showed higher response rate and longer survival.The toxicities during EGFR-TKI treatments were low,and could be controllable after symptomatic treatment.Administration of EGFR-TKI combined radiotherapy conferred minimum influence on radiotherapy.

Drug resistance of EGFR-TKI for non-small cell lung cancer / 中国肿瘤临床

The incidence of lung cancer ranks the first among malignancies in China. Studies on molecular-targeted therapy with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have atracted more attention. However, many patients with non-small cell lung cancer (NSCLC) manifest primary symptoms at the beginning of therapy;other patients develop drug resistance after they receive EGFR-TKI treatment for a period. This review describes the progress on drug resistance mechanisms of EGFR-TKIs at a molecular level and the significance of such inhibitors in clinical application.

Efficacy of EGFR-TKI and chemotherapy in advanced non-small cell lung cancer with EGFR-TKI resistence / 中国癌症杂志

Background and purpose:New treatment strategies should be explored for non-small cell lung cancer (NSCLC) patients after the failure of the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). To compare the efficacy and toxicities of chemotherapy in combination with EGFR-TKI or single chemotherapy in advanced NSCLC patients with EGFR-TKI resistence. Methods:In this study, 18 patients were enrolled. Eight patients were treated by chemotherapy combined with EGFR-TKI (CE group);10 patients were treated by single chemotherapy (E group), 21 days for one cycle. All patients received at least 2 cycles of treatment. Results:All 18 patients had been evaluated. The CE group was similar to the E group in objective response rate (ORR:25%vs 10%, P=0.832). The CE group was higher than the E group in disease control rate (DCR:87.5%vs 30%, P=0.046). The median PFS was longer in CE group (3.5 months vs 2.4 months, P=0.05). The CE group was higher than the E group in rash (75%vs 10%, P0.05). Conclusion:Though there was no significant difference in ORR between the 2 groups (P>0.05), the CE group was superior to the E group in DCR and PFS. Patients with retreatment of advanced NSCLC after the failure of EGFR-TKI can be controlled by continued EGFR-TKI and chemotherapy.

The Role of Pharmacoethnicity in the Development of Cytotoxic and Molecular Targeted Drugs in Oncology

The effective and toxic ranges of anticancer drugs are very narrow and, in some cases, inverted. Thus determination of the most appropriate dosage and schedule of administration is crucial for optimal chemotherapy. In common arm trials conducted in Japan and by Southwest Oncology Group (SWOG) that used the same doses and schedules for the administration of carboplatin plus paclitaxel, the frequency of hematological toxicity was significantly higher in the Japanese trials than in the SWOG trial, despite demonstrating similar response rates. The frequency of epidermal growth factor receptor (EGFR) mutations in tumors was significantly higher among East Asian populations, and these populations are also reported to demonstrate a higher response rates to epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs). The prevalence of interstitial lung disease induced by treatment with EGFR-TKIs has been shown to be quite high in the Japanese population. Clinical trials of cetuximab against non-small cell lung cancer and of bevacizumab against stomach cancer have shown that these agents are only active in Caucasians. In a trial examining the use of sorafenib after transarterial chemoembolization in Korean and Japanese patients with advanced hepatocellular carcinoma, the compliance and dose intensity of the drug were quite low compared with other trials. Although not only identified pharmacogenomics differences but also differences in social environment, and regional medical care, including pharmacoeconomics strongly influence ethnic differences in treatment response, further identification and understanding of the pharmacogenomics underlying ethnic differences will be essential to timely and reliable global development of new anticancer drugs.

Continuous treatment with EGFR-TKI in the terminal stage for non-small cell lung cancer patients who initially responded to EGFR-TKI

<b>Purpose</b>: We evaluated the efficacy of continuous administration of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in patients with end-stage non-small cell lung cancer. <b>Method</b>: Our study included 33 patients most recently treated with EGFR-TKI for non-small cell lung cancer that had once been responsive to EGFR-TKI but eventually showed worsening. We compared patients who discontinued EGFR-TKI within one month (n=16) after their disease progressed and those who continued the treatment (n=17). <b>Results</b>: The median survival time was significantly longer in patients who continued EGFR-TKI (191 days) than in those who discontinued the treatment (62 days) (p=0.0098). Adverse events experienced by patients who continued the treatment included Grade 1 eruption in six, Grade 2 eruption in one, Grade 1 diarrhea in one and Grade 1 AST/ALT elevation in four. All of these adverse events were manageable. <b>Conclusion</b>: In patients with non-small cell lung cancer initially responsive to EGFR-TKI but eventually showing worsening and becoming unfit for cytotoxic anticancer drugs, continuous administration of EGFR-TKI may extend their survival with acceptable toxicity. Further investigation of this strategy is warranted. Palliat Care Res 2011; 6(1): 119-125