Pneumatosis intestinalis (PI) is a rare condition that is characterized by multiple subserosal and submucosal gas-filled areas in the bowel wall. Gastric pneumatosis describes the presence of gas within the stomach wall. This is caused by a disruption in gastric mucosa leading to the dissection of air into the wall. The extract cause of PI is still unknown; however, it may be associated with coexisting disease. Gastric PI has been rarely documented. So, we report on a 75-year-old man with acute gastric pneumatosis following his palliative chemotherapy. He underwent 3rd cycle of gemcitabine and erlotinib 3 weeks prior to admission. The treatment was started with nasogastric tube insertion and parenteral nutrition. Then, gastric pneumatosis was improved. However, the patient was died because of worsening underline disease and general condition. We suggest that chemotherapy should be considered the case of pneumatosis and careful X-ray interpretation will be necessary for detecting the pneumatosis earlier.
Aged ; Drug Therapy ; Gastric Mucosa ; Humans ; Pancreatic Neoplasms* ; Parenteral Nutrition ; Stomach ; Erlotinib Hydrochloride

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.
Asia ; Carcinoma, Non-Small-Cell Lung ; Humans ; Lung Diseases, Interstitial ; Lung Neoplasms ; Quinazolines ; Recurrence ; Erlotinib Hydrochloride

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.
Asia ; Carcinoma, Non-Small-Cell Lung ; Humans ; Lung Diseases, Interstitial ; Lung Neoplasms ; Quinazolines ; Recurrence ; Erlotinib Hydrochloride

A patient with adenocarcinoma of the lung was treated sequentially using two kinds of EGFR tyrosine kinase inhibitors, gefitinib and erlotinib. The patient was a 73-year-old female who received gefitinib as a second line treatment, which resulted in a partial response with response duration of 6 months. After progression of the disease, the patient received erlotinib, which resulted in partial response again with response duration of 11.5 months. This observation suggests that treatment with erlotinib may be effective in patients who develop progressive disease after a primary treatment with gefitinib following an initial response.
Adenocarcinoma* ; Aged ; Female ; Humans ; Lung Neoplasms ; Lung* ; Protein-Tyrosine Kinases ; Erlotinib Hydrochloride

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.
Accounting ; Adenocarcinoma ; Disease Progression ; Humans ; Korea ; Lung ; Lung Neoplasms ; Pneumothorax ; Quinazolines ; Erlotinib Hydrochloride

PURPOSE: To report the corneal superficial punctate keratoepitheliopathy in 2 patients taking the epidermal growth factor receptor (EGFR) inhibitors, erlotinib and lapatinib, respectively. CASE SUMMARY: Case 1, who received erlotinib, showed trichomegaly without touching the cornea and diffuse punctate keratoepitheliopathy. Corneal epitheliopathy and the corresponding symptoms resolved after discontinuation of the drug then recurred with reapplication. Case 2 presented diffuse corneal punctate epithelial erosions that developed without any cilia involvement after the patient was administered lapatinib. The visual acuity of both patients was not severely diminished and keratoepitheliopathy was mostly resolved with the treatment of preservative-free artificial tears and autologous serum eye drops. CONCLUSIONS: Erlotinib and lapatinib are both likely to cause visually tolerable corneal punctate keratoepitheliopathy which can be resolved with appropriate topical treatment.
Cilia ; Cornea ; Epidermal Growth Factor ; Humans ; Ophthalmic Solutions ; Receptor, Epidermal Growth Factor ; Visual Acuity ; Erlotinib Hydrochloride

BACKGROUND: Therapeutic approach by treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) like gefitinib or erlotinib to non-small cell lung cancer (NSCLC) patients has been limited due to emergence of acquired drug resistance. Our study was aimed to investigate whether the inhibition of ubiquitin-specific peptidase 8 (USP8) could be an alternative strategy capable of overcoming acquired resistance to EGFR-TKIs for treatment of NSCLCs. METHODS: The anticancer effect of USP8 inhibitor was determined by testing anchorage-dependent or independent growth of gefitinib-sensitive or resistant NSCLCs. The immunoprecipitation and western blotting were conducted to check molecular interaction and signaling pathway followed by USP8 inhibition. RESULTS: Inhibition of USP8 induced overall degradation of oncogenic receptor tyrosine kinases including EGFR and Met, leading to a suppression of anchorage-dependent or independent cell growth of gefitinib-sensitive or resistant NSCLCs. Also, treatment with the USP8 inhibitor markedly induced apoptosis in HCC827GR cells. Notably, treatment with the USP8 inhibitor was more effective in suppressing cell growth and inducing apoptosis in gefitinib-resistant HCC827GR cells than that of gefitinib-sensitive HCC827 cells. CONCLUSIONS: Inhibition of USP8 could be an effective strategy for overcoming gefitinib resistance in NSCLCs.
Apoptosis* ; Blotting, Western ; Carcinoma, Non-Small-Cell Lung* ; Drug Resistance ; Epidermal Growth Factor ; Erlotinib Hydrochloride ; Humans ; Immunoprecipitation ; Phosphotransferases ; Tyrosine

PURPOSE: Concurrent chemoradiotherapy (CCRT) is the standard care for stage III non-small cell lung cancer (NSCLC) patients; however, a more effective regimen is needed to improve the outcome by better controlling occult metastases. We conducted two parallel randomized phase II studies to incorporate erlotinib or irinotecan-cisplatin (IP) into CCRT for stage III NSCLC depending on epidermal growth factor receptor (EGFR) mutation status. MATERIALS AND METHODS: Patients with EGFR-mutant tumors were randomized to receive three cycles of erlotinib first and then either CCRT with erlotinib followed by erlotinib (arm A) or CCRT with IP only (arm B). Patients with EGFR unknown or wild-type tumors were randomized to receive either three cycles of IP before (arm C) or after CCRT with IP (arm D). RESULTS: Seventy-three patients were screened and the study was closed early because of slow accrual after 59 patients were randomized. Overall, there were seven patients in arm A, five in arm B, 22 in arm C, and 25 in arm D. The response rate was 71.4% and 80.0% for arm A and B, and 70.0% and 73.9% for arm C and D. The median overall survival (OS) was 39.3 months versus 31.2 months for arm A and B (p=0.442), and 16.3 months versus 25.3 months for arm C and D (p=0.050). Patients with sensitive EGFR mutations had significantly longer OS than EGFR-wild patients (74.8 months vs. 25.3 months, p=0.034). There were no unexpected toxicities. CONCLUSION: Combined-modality treatment by molecular diagnostics is feasible in stage III NSCLC. EGFR-mutant patients appear to be a distinct subset with longer survival.
Arm ; Carcinoma, Non-Small-Cell Lung* ; Chemoradiotherapy* ; Cisplatin* ; Erlotinib Hydrochloride* ; Humans ; Neoplasm Metastasis ; Pathology, Molecular ; Receptor, Epidermal Growth Factor

Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib and erlotinib show good response and survival benefit in EGFR-mutant lung cancer, acquired resistance inevitably develops which limits the median response duration to around 1 year. Secondary T790M gatekeeper mutation is the most common mechanism representing approximately 50% of resistance. The suggested strategies for overcoming T790M including irreversible EGFR-TKIs, mutant-selective EGFR-TKIs, EGFR dual targeting and HSP90 inhibitors should be further investigated for clinical application. Bypass signals through MET or AXL also contribute to resistance, which lead to development of MET or AXL inhibitors. Other mechanisms such as small cell transformation, epithelial-to-mesenchymal transition, PI3KCA mutation, ERK/HER2 amplification and miRNAs are other suggested candidates awaiting validation. As many resistant mechanisms have been recognized, it is important to obtain tissue samples after resistance to provide appropriate treatment. In this review, recent advances in the understanding of resistance and novel ways of overcoming it are discussed.
Drug Resistance ; Epidermal Growth Factor ; Lung ; Lung Neoplasms ; MicroRNAs ; Protein-Tyrosine Kinases ; Quinazolines ; Receptor, Epidermal Growth Factor ; Erlotinib Hydrochloride

Personalized cancer medicine aims to accurately predict the response of individual patients to targeted therapies, including tyrosine kinase inhibitors (TKIs). Clinical implementation of this concept requires a robust selection tool. Here, using both cancer cell lines and tumor tissue from patients, we evaluated a high-throughput tyrosine kinase peptide substrate array to determine its readiness as a selection tool for TKI therapy. We found linearly increasing phosphorylation signal intensities of peptides representing kinase activity along the kinetic curve of the assay with 7.5–10 μg of lysate protein and up to 400 μM adenosine triphosphate (ATP). Basal kinase activity profiles were reproducible with intra- and inter-experiment coefficients of variation of <15% and <20%, respectively. Evaluation of 14 tumor cell lines and tissues showed similar consistently high phosphorylated peptides in their basal profiles. Incubation of four patient-derived tumor lysates with the TKIs dasatinib, sunitinib, sorafenib and erlotinib primarily caused inhibition of substrates that were highly phosphorylated in the basal profile analyses. Using recombinant Src and Axl kinase, relative substrate specificity was demonstrated for a subset of peptides, as their phosphorylation was reverted by co-incubation with a specific inhibitor. In conclusion, we demonstrated robust technical specifications of this high-throughput tyrosine kinase peptide microarray. These features required as little as 5–7 μg of protein per sample, facilitating clinical implementation as a TKI selection tool. However, currently available peptide substrates can benefit from an enhancement of the differential potential for complex samples such as tumor lysates. We propose that mass spectrometry-based phosphoproteomics may provide such an enhancement by identifying more discriminative peptides.
Adenosine Triphosphate ; Cell Line ; Cell Line, Tumor ; Dasatinib ; Erlotinib Hydrochloride ; Humans ; Peptides ; Phosphorylation ; Phosphotransferases ; Protein-Tyrosine Kinases* ; Substrate Specificity ; Tyrosine*