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*

Multi-target anticancer drugs have a more comprehensive and extensive range of action,and there is an uncertain risk in the combination of two drugs.A case of acute toxicity induced by erlotinib combined with cabozantinib is reported in this article.
Anilides ; adverse effects ; Drug Eruptions ; etiology ; Drug Therapy, Combination ; adverse effects ; Erlotinib Hydrochloride ; adverse effects ; Humans ; Myocardial Infarction ; chemically induced ; Pyridines ; adverse effects

PURPOSE: Despite the successful use of tyrosine kinase inhibitors (TKIs) in cancer patients, their effect on herpes zoster development has not been studied. The aim of this study was to evaluate and compare the effects of epidermal growth factor receptor (EGFR) TKI and cytotoxic chemotherapy on the risk of herpes zoster development in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: We conducted a medical review of all eligible NSCLC patients in Seoul National University hospital between 2002 and 2015. We classified patients based on whether they previously underwent EGFR TKI therapy into either the TKI group or the cytotoxic group. We compared the incidence rates of herpes zoster during TKI therapy and cytotoxic chemotherapy. Additionally, the longitudinal risk of herpes zoster from TKIs was analyzed using the incidence rate ratio (IRR) of the TKI group to the cytotoxic group and the log-rank test of the Kaplan-Meier method. RESULTS: Of the 2,981 NSCLC patients, 54 patients (1.54%) developed herpes zoster. In the TKI group (2,002 patients), the IRR of herpes zoster during TKI therapy compared to that during cytotoxic chemotherapy was 1.05 (95% confidence interval [CI], 0.53 to 2.09). The IRR of the TKI group compared to the cytotoxic group was 1.33 (95% CI, 0.64 to 2.76). The Kaplan-Meier cumulative risk of both groups was not significantly different. CONCLUSION: Our results show that the incidence rate of herpes zoster in the TKI group was not statistically different from the incidence in the cytotoxic group during and after chemotherapy in NSCLC patients.
Carcinoma, Non-Small-Cell Lung* ; Drug Therapy* ; Erlotinib Hydrochloride ; Herpes Zoster* ; Humans ; Incidence ; Methods ; Protein-Tyrosine Kinases* ; Receptor, Epidermal Growth Factor ; Seoul ; Tyrosine*

PURPOSE: We tried to evaluate whether there are any specific features in treatment outcomes of firstline afatinib in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), compared with gefitinib or erlotinib. MATERIALS AND METHODS: We analyzed patients treated with first-line afatinib, gefitinib, or erlotinib for advanced EGFR-mutant NSCLC at Samsung Medical Center between 2014 and 2016. RESULTS: In total, 467 patients received first-line afatinib (n=165), gefitinib (n=230), or erlotinib (n=72). Afatinib was used more often in patients with tumors harboring deletion in exon 19 (Del19), whereas the gefitinib group had more elderly, females, and never smokers. The median progression-free survival (PFS) time for afatinib, gefitinib, and erlotinib was 19.1 months, 13.7 months, and 14.0 months, respectively (p=0.001). The superior PFS of afatinib was more remarkable in subgroups of Del19 or uncommon EGFR mutations. Overall toxicity profiles of the three drugs were comparable, though more grade 3 or 4 toxicities were detected in afatinib (7.3%) compared with gefitinib (2.6%) or erlotinib (1.8%). The common grade 3 or 4 toxicities of afatinib included diarrhea (3.0%), paronychia (2.4%), and skin rash (1.8%). Dose modification was more frequently required in patients treated with afatinib (112/165, 68%), compared with gefitinib (5/230, 2%) and erlotinib (4/72, 6%). Interestingly, however, dose reduction in the afatinib group did not impair its efficacy in terms of PFS (dose reduction vs. no reduction group, 23.5 months vs. 12.4 months). CONCLUSION: First-line afatinib showed satisfactory efficacy data and manageable toxicity profiles.
Aged ; Carcinoma, Non-Small-Cell Lung ; Diarrhea ; Disease-Free Survival ; Erlotinib Hydrochloride ; Exanthema ; Exons ; Female ; Humans ; Paronychia ; Receptor, Epidermal Growth Factor

PURPOSE: This study was conducted to evaluate the relationship between epidermal growth factor receptor (EGFR) mutation and clinical outcomes in patients with stage III non-squamous cell lung cancer treated with definitive concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: From January 2008 to December 2013, the medical records of 197 patients with stage III non- squamous non-small cell lung cancer treated with definitive CCRT were analyzed to determine progression-free survival (PFS) and overall survival (OS) according to EGFR mutation status. RESULTS: Among 197 eligible patients, 81 patients were EGFR wild type, 36 patients had an EGFR mutation (exon 19 Del, n=18; L858R, n=9, uncommon [G719X, L868, T790M], n=9), and 80 patients had unknown EGFR status. The median age was 59 years (range, 28 to 80 years) and 136 patients (69.0%) were male. The median follow-up duration was 66.5 months (range, 1.9 to 114.5 months). One hundred sixty-four patients (83.2%) experienced disease progression. Median PFS was 8.9 months for the EGFR mutation group, 11.8 months for EGFR wild type, and 10.5 months for the unknown EGFR group (p=0.013 and p=0.042, respectively). The most common site of metastasis in the EGFR mutant group was the brain. However, there was no significant difference in OS among the three groups (34.6 months for EGFR mutant group vs. 31.9 months for EGFR wild type vs. 22.6 months for EGFR unknown group; p=0.792 and p=0.284). A total of 29 patients (80.6%) with EGFR mutation were treated with EGFR tyrosine kinase inhibitor (gefitinib, n=24; erlotinib, n=3; afatinib, n=2) upon progression. CONCLUSION: EGFR mutation is associatedwith short PFS and the brain is the most common site of distant metastasis in patients with stage III non- squamous cell lung cancer treated with CCRT.
Brain ; Carcinoma, Non-Small-Cell Lung ; Chemoradiotherapy ; Disease Progression ; Disease-Free Survival ; Epithelial Cells ; Erlotinib Hydrochloride ; Follow-Up Studies ; Humans ; Lung Neoplasms ; Lung ; Male ; Medical Records ; Neoplasm Metastasis ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor

PURPOSE: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare genetic syndrome resulting from germline mutations in fumarate hydratase. The combination of bevacizumab plus erlotinib showed promising interim results for HLRCC-associated RCC. Based on these results, we analyzed the outcome of bevacizumab plus erlotinib in Korean patients with HLRCC-associated RCC. MATERIALS AND METHODS: We retrospectively reviewed the efficacy and safety of bevacizumab plus erlotinib in patients with HLRCC-associated RCC who were confirmed to have germline mutations in fumarate hydratase. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULT: We identified 10 patients with advanced HLRCC-associated RCC who received bevacizumab plus erlotinib. Median age at diagnosis was 41 years, and five of the patients had received the combination as first- or second-line treatments. The ORR was 50% and the median PFS and OS were 13.3 and 14.1 months, respectively. Most adverse events were predictable and manageable by conventional measures, except for one instance where a patient died of gastrointestinal bleeding. CONCLUSION: This is the first real-world outcome of the treatment of advanced HLRCC-associated RCC. Bevacizumab plus erlotinib therapy showed promising activity with moderate toxicity. We should be increasingly aware of HLRCC-associated RCC and bevacizumab plus erlotinib should be a first-line treatment for this condition, unless other promising data are published.
Bevacizumab ; Carcinoma, Renal Cell ; Diagnosis ; Disease-Free Survival ; Erlotinib Hydrochloride ; Fumarate Hydratase ; Germ-Line Mutation ; Hemorrhage ; Humans ; Leiomyomatosis ; Retrospective Studies

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

Erlotinib inhibits the epidermal growth factor receptor and is used in patients with various cancers. However, it can affect the epidermis and hair because the receptor is expressed in normal skin cells. A 54-year-old woman with metastatic non-small-cell lung cancer presented with erythematous patches over her entire body and severe hair shedding 2 weeks after starting erlotinib. Histopathological examinations showed lymphocytic exocytosis; perivascular infiltration of lymphohistiocytes and eosinophils in the right arm; and marked infiltration of eosinophils, neutrophils, and lymphohistiocytes in the scalp. Erlotinib discontinuation improved hair loss and skin lesions. Hair loss has been reported in 5% of patients taking erlotinib. Our case was unusual in that there was complete baldness, and to our knowledge, no report of complete hair loss and exanthematous drug eruption after erlotinib treatment has been previously reported. Here, we report a case of severe hair loss with concurrent exanthematous drug eruption that may have been linked to erlotinib hypersensitivity.
Alopecia ; Arm ; Drug Eruptions ; Eosinophils ; Epidermis ; Erlotinib Hydrochloride ; Exocytosis ; Female ; Hair ; Humans ; Hypersensitivity ; Lung Neoplasms ; Middle Aged ; Neutrophils ; Receptor, Epidermal Growth Factor ; Scalp ; Skin

The effects of tyrosine kinase inhibitors (TKIs) were evaluated on growth inhibition of intracellular Toxoplasma gondii in host ARPE-19 cells. The number of tachyzoites per parasitophorous vacuolar membrane (PVM) was counted after treatment with TKIs. T. gondii protein expression was assessed by western blot. Immunofluorescence assay was performed using Programmed Cell Death 4 (PDCD4) and T. gondii GRA3 antibodies. The TKIs were divided into 3 groups; non-epidermal growth factor receptor (non-EGFR), anti-human EGFR 2 (anti-HER2), and anti-HER2/4 TKIs, respectively. Group I TKIs (nintedanib, AZD9291, and sunitinib) were unable to inhibit proliferation without destroying host cells. Group II TKIs (lapatinib, gefitinib, erlotinib, and AG1478) inhibited proliferation up to 98% equivalent to control pyrimethamine (5 μM) at 20 μM and higher, without affecting host cells. Group III TKIs (neratinib, dacomitinib, afatinib, and pelitinib) inhibited proliferation up to 98% equivalent to pyrimethamine at 1–5 μM, but host cells were destroyed at 10–20 μM. In Group I, TgHSP90 and SAG1 inhibitions were weak, and GRA3 expression was moderately inhibited. In Group II, TgHSP90 and SAG1 expressions seemed to be slightly enhanced, while GRA3 showed none to mild inhibition; however, AG1478 inhibited all proteins moderately. Protein expression was blocked in Group III, comparable to pyrimethamine. PDCD4 and GRA3 were well localized inside the nuclei in Group I, mildly disrupted in Group II, and were completely disrupted in Group III. This study suggests the possibility of a vital T. gondii TK having potential HER2/4 properties, thus anti-HER2/4 TKIs may inhibit intracellular parasite proliferation with minimal adverse effects on host cells.
Antibodies ; Blotting, Western ; Cell Death ; Epidermal Growth Factor* ; Erlotinib Hydrochloride ; Fluorescent Antibody Technique ; Humans* ; Membranes ; Parasites ; Protein-Tyrosine Kinases ; Pyrimethamine ; Receptor, Epidermal Growth Factor* ; Toxoplasma

BACKGROUND: A number of anticancer agents are known to induce many adverse reactions in the skin. Related cutaneous adverse drug reactions influence the morbidity, mortality, and anti-cancer regimen of the patients. A multidisciplinary approach to cancer management has been emphasized. OBJECTIVE: To identify the causative anticancer agents and frequency of adverse reactions in the skin. METHODS: We retrospectively reviewed the medical records of patients who consulted at the Dermatology Department of Busan Paik Hospital and Haeundae Paik Hospital from January 2013 to February 2015. RESULTS: A total of 140 patients were enrolled. Among the 45 patients treated with antimetabolite analogs (30 cytarabine, 7 gemcitabine, 3 methotrexate, 2 fludarabine, 2 doxifluridine, and 1 decitabine), exanthematous drug eruption (49.1%) was the most common reaction, followed by hand-foot syndrome (28.3%). Among the 35 patients treated with fluorouracil (22 5-fluorouracil and 13 capecitabine), hand-foot syndrome (47.2%) was the most common, followed by acneiform eruption (25.0%). Among the 24 patients treated with epidermal grow factor receptor inhibitors (10 erlotinib, 10 cetuximab, and 4 gefitinib), acneiform eruption (54.8%) was the most common, followed by xerosis (19.4%). Among the 11 patients treated with anthracyclines (9 doxorubicin, 1 daunorubicin, and 1 idarubicin), acneiform eruption (45.5%) was the most common, followed by hand-foot syndrome (36.4%). Among the 7 patients treated with taxanes (4 docetaxel and 3 paclitaxel), hand-foot syndrome (42.8%) was the most common. Among the 6 patients treated with angiogenesis-inducing inhibitors (3 sorafenib, 2 pazopanib, and 1 sunitinib), hand-foot skin reaction (66.7%) was the most common. Only 2 patients (1.4%) changed treatments due to intolerable skin reactions. CONCLUSION: Clinicians should be aware of the various skin reactions of anticancer agents and predict their clinical course effectively.
Acneiform Eruptions ; Anthracyclines ; Antineoplastic Agents ; Busan ; Cetuximab ; Cytarabine ; Daunorubicin ; Dermatology ; Doxorubicin ; Drug Eruptions ; Drug-Related Side Effects and Adverse Reactions ; Erlotinib Hydrochloride ; Fluorouracil ; Hand-Foot Syndrome ; Humans ; Medical Records ; Methotrexate ; Mortality ; Retrospective Studies* ; Skin ; Taxoids