• Tuberculosis and Respiratory Diseases
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• v.67 no.5
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• pp.445-448
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• 2009

Erlotinib ($Tarceva^{(R)}$) has been considered to be a new, promising oral chemotherapy agent for local advanced or metastatic non-small cell lung cancer (NSCLC). Erlotinib is regarded as relatively safe, but interstitial lung disease (ILD) related to erlotinib has been reported on an infrequent basis in Asia. We report an histologically confirmed case of recurrent erlotinib-induced ILD. Although, the patient was highly responsive to the first erlotinib treatment, the therapy was discontinued due to erlotinib-induced ILD. After intravenous high dose methylpredinisolone treatment, ILD was improved rapidly by radiologic studies, but the particular lung cancer re-emerged. We restarted the patient erlotinib on low-dose oral methylpredinisolone, resulting in a recurrence of erlotinib-induced ILD. Our case suggests that re-administration of erlotinib should be performed on a limited basis in patients that have developed ILD on previous use, even if a therapeutic effect can be estimated.

• Tuberculosis and Respiratory Diseases
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• v.66 no.4
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• pp.280-287
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• 2009

Background: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), became an attractive therapeutic option for advanced non-small-cell lung cancer (NSCLC). Several studies suggested that there might be some different efficacy or response predictors between gefitinib and erlotinib. We compared the efficacy and toxicity of gefitinib and erlotinib in Korean patients with advanced NSCLC and evaluated specific predictors of response for both gefitinib and erlotinib. Methods: We collected the clinical information on patients with advanced NSCLC, who were treated with gefitinib or erlotinib at the Ewha Womans University Hospital, between July 2003 and February 2009. Median survival times were calculated using the Kaplan-Meier method. Results: Eighty-six patients (52 gefitinib vs. 34 erlotinib) were enrolled. Patient median age was 64 years; 53 (62%) subjects were male. Out of the 86 patients treated, 83 received response evaluation. Of the 83 patients, 35 achieved a response and 12 experienced stable disease while 36 experienced progressive disease, resulting in a response rate of 42% and a disease control rate of 57%. After a median follow-up of 502 days, the median progression-free and overall survival time was 129 and 259 days, respectively. Comparing patients by treatment (gefitinib vs erlotinib), there were no significant differences in the overall response rate (44% vs. 39%, p=0.678), median survival time (301 days vs. 202 days, p=0.151), or time to progression (136 days vs. 92 days, p=0.672). Both EGFR-TKIs showed similar toxicity. In a multivariate analysis using Cox regression model, adenocarcinoma was an independent predictor of survival (p=0.006; hazard ratio [HR], 0.487; 95% confidence interval [CI], 0.292-0.811). Analyses of subgroups did not show any difference in response predictors between gefitinib and erlotinib. Conclusion: Comparing gefitinib to erlotinib, there were no differences in the response rate, overall survival, progression-free survival, or toxicity. No specific predictor of response to each EGFR-TKI was identified.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10281-10287
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• 2015

Background: Development of a nanosized polymeric delivery system for erlotinib was the main objective of this research. Materials and Methods: Poly caprolactone-polyethylene glycol-polycaprolactone (PCEC) copolymers with different compositions were synthesized via ring opening polymerization. Formation of triblock copolymers was confirmed by HNMR as well as FT-IR. Erlotinib loaded nanoparticles were prepared by means of synthesized copolymers with solvent displacement method. Results: Physicochemical properties of obtained polymeric nanoparticles were dependent on composition of used copolymers. Size of particles was decreased with decreasing the PCL/PEG molar ratio in used copolymers. Encapsulation efficiency of prepared formulations was declined by decreasing their particle size. Drug release behavior from the prepared nanoparticles exhibited a sustained pattern without a burst release. From the release profiles, it can be found that erlotinib release rate from polymeric nanoparticles is decreased by increase of CL/PEG molar ratio of prepared block copolymers. Based on MTT assay results, cell growth inhibition of erlotinib has a dose and time dependent pattern. After 72 hours of exposure, the 50% inhibitory concentration (IC50) of erlotinib hydrochloride was appeared to be $14.8{\mu}M$. Conclusions: From the obtained results, it can be concluded that the prepared PCEC nanoparticles in this study might have the potential to be considered as delivery system for erlotinib.

• Tuberculosis and Respiratory Diseases
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• v.71 no.4
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• pp.286-290
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• 2011

Although failure of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) is generally believed to be associated with cross-resistance to other EGFR TKI, the benefit of administering erlotinib as a second EGFR TKI after resistance of gefitinib as the first TKI has been well known. However, good response to gefitinib after an initial response to erlotinib has been rare. We report that a 45-year-old woman (never smoked), with lung adenocarcinoma and EGFR mutation, showed an initial response to erlotinib, and then responded to gefitinib again.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3471-3476
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• 2012

Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.71 no.1
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• pp.15-23
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• 2011

Background: Gefitinib and erlotinib are useful, molecular targeted agents in patients with non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. We compared the efficacy and toxicity of two drugs in patients with squamous cell lung cancer, most of whom are male smokers. Methods: We retrospectively reviewed the clinical information on patients with NSCLC who were treated with gefitinib or erlotinib treatment at Chonnam National University Hwasun Hospital between July 2002 and November 2009. The overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) were compared between the two drugs. Results: A total of 182 (100 gefitinib vs. 82 erlotinib) of 584 patients treated by targeted agents had squamous histology. Of the 182 patients, 167 (91.7%) were male and 159 (87.4%) were smokers. The ORR and disease control rate (DCR) were 4.9% and 40.6%, and there was no significant difference between gefitinib and erlotinib (ORR, 5.0% vs 4.8%; p=0.970; DCR, 40.0% vs 41.4%; p=0.439). The median OS in the gefitinib group was 12.1 months, and that in the erlotinib was 12.7 months (hazard ratio [HR], 1.282; 95% confidence interval [CI], 0.771~2.134; p=0.339). The median PFS for the gefitinib group was 1.40 months, compared with 1.37 months for the erlotinib group (HR, 1.092; 95% CI, 0.809~1.474; p=0.564). Skin rash ${\geq}$grade 3 was more common in erlotinib (12.2%) than gefitinib (1.0%, p=0.003) groups. Conclusion: This retrospective study showed that the two drugs appear to have similar antitumor efficacy and toxicity except for skin rash.

• Bulletin of the Korean Chemical Society
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• v.32 no.3
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• pp.909-914
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• 2011

An improved convergent and economical method has been developed for the synthesis of erlotinib, a 4-anilinoquinazoline and an EGFR-tyrosine kinase inhibitor for treatment of non-small-cell lung cancer. The final two steps for the formation of this 4-anilinoquinazoline from suitable 2-aminobenzonitrile intermediate and 3-ethynylaniline were modified and were performed in a simple one-pot reaction. The ring-closing mechanism for the formation of erlotinib from the suitable formamidine intermediate and 3-ethynylaniline was investigated and determined to proceed via the formation of phenyl benzamidine intermediate rather than involving Dimroth rearrangement reported earlier. The new benzamidine intermediate was isolated for the first time and characterized.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3255-3261
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• 2013

Background: The efficacy of erlotinib is controversial in patients with unknown EGFR mutational status. The aim of this study was to identify the clinicopathological factors that are predictive of erlotinob treatment outcomes for NSCLC patients with unknown EGFR mutational status. Materials and Methods: A retrospective analysis of 109 patients with advanced NSCLC who had previously failed at least one line of chemotherapy and received subsequent treatment with erlotinib (150 mg/day orally) was performed. A Cox proportional hazard model for univariate and multivariate analyses was used to identify the baseline clinical parameters correlating with treatment outcome, expressed in terms of hazard ratios (HRs) and 95% confidence intervals. Results: The median treatment duration was 15 weeks (range, 4-184). The disease control rate was 55%, including disease stability for ${\geq}3$ months for 40% of the patients. Median progression-free survival and median overall survival (OS) were 4.2 and 8.5 months, respectively. The Cox model indicated that an Eastern Cooperative Oncology Group performance status (ECOG PS) ${\geq}2$ (HR 3.82; p<0.001), presence of intra-abdominal metastasis (HR 3.42; p=0.002), 2 or more prior chemotherapy regimens (HR 2.29; p=0.021), and weight loss >5% (HR 2.05; p=0.034) were independent adverse prognostic factors for OS in NSCLC patients treated with erlotinib. Conclusions: This study suggests that NSCLC patients should be enrolled in erlotinib treatment after a first round of unsuccessful chemotherapy to improve treatment success, during which they should be monitored for intra-abdominal metastasis and weight loss.

• Tuberculosis and Respiratory Diseases
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• v.69 no.6
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• pp.465-468
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• 2010

Spontaneous pneumothorax (SPTx) associated with primary lung cancer is quite rare, but has been reported as the initial presentation or a complication of disease progression. Moreover, chemotherapy-related SPTx in primary lung cancer occurs at a very low frequency, accounting for less than 0.05% of all cases. Here, we report the first case of erlotinib-related SPTx in a patient with advanced lung adenocarcinoma in Korea. After 3 cycles of cisplatin-based chemotherapy as first-line therapy, erlotinib was administered as second-line treatment. Asymptomatic SPTx accompanied by a significant decrease in tumor size was observed in the left lung 7 weeks later. The patient received continuous administration of erlotinib, without additional treatment. This case showed that SPTx can occur in patients with primary lung cancer receiving erlotinib, and asymptomatic chemotherapy-related SPTx in primary lung cancer may not require therapeutic intervention.

• The Journal of Internal Korean Medicine
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• v.43 no.5
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• pp.838-853
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• 2022

Objectives: The purpose of this study is to report the case of a patient with recurrent L858R mutation non-small-cell lung cancer with brain metastases treated with erlotinib and traditional Korean medicine after gefitinib failure. Methods: The patient was treated with erlotinib beginning in November 2021, and gamma knife surgery was performed on November 8, 2021. The dose of erlotinib was 150 mg/day every four weeks. At the same time, the patient was treated with traditional Korean medicine. Tumor size and cerebral edema were measured using computed tomography and magnetic resonance imaging, respectively. Adverse events were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Results: After treatment with erlotinib and traditional Korean medicine for six months, the extent of the growing nodule in the right upper lobe decreased during the first three months and remained stable for the following three months. Peritumoral edema showed an increase three months after gamma knife surgery, but partial improvement of cerebral edema was confirmed with additional traditional Korean medicine six months after gamma knife surgery. The symptoms of discomfort and physical activity gradually improved. Conclusions: This case study suggests that the combination of EGFR-TKI and traditional Korean medicine may contribute to a reduction in tumor size and cerebral edema while improving quality of life.