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Background & objectives: Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) have been evaluated in patients with advanced non-small cell lung cancer (NSCLC). Erlotinib and gefitinib are the first-generation EGFR-TKIs for patients with NSCLC. However, there is a paucity of studies comparing the effectiveness of these two drugs. Hence, this study was aimed to compare the effectiveness and safety of erlotinib and gefitinib in NSCLC patients. Methods: This study included 71 NSCLC patients who received EGFR-TKIs between 2013 and 2016. Adverse drug reaction of both erlotinib (n=37) and gefitinib (n=34) was determined and graded according to Common Terminology Criteria for Adverse Events grading system. Effectiveness was measured using response evaluation criteria in solid tumours and progression-free survival (PFS). Pharmacoeconomic analysis was performed by cost-effective analysis. Results: When comparing safety profile, both the drugs had similar adverse events except for dermal side effects such as acneiform eruption (51.4%), rash (54.05%) and mucositis (59.5%) for erlotinib and 20.6, 26.5 and 29.4 per cent for gefitinib, respectively. The PFS of the two drugs was compared to differentiate the effectiveness of erlotinib and gefitinib. There was no significant difference between the effectiveness of the two drugs. The pharmacoeconomic analysis showed that gefitinib was more cost-effective than erlotinib. Interpretation & conclusions: This study showed that erlotinib and gefitinib had similar effectiveness but gefitinib had a better safety profile compared to erlotinib. Therefore, gefitinib could be considered a better option for NSCLC patients compared to erlotinib. However, further studies need to be done with a large sample to confirm these findings.
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Objective The aim of this study was to investigate the mechanism underlying pruritus by comparing the epidermal growth factor receptor inhibitor(EGFRI)-erlotinib mouse model with the substance P(SP)-induced pruritus mouse model. Methods Two randomized groups of mice were treated with erlotinib or SP to induce pruritus. Behavioral and skin manifestations were observed. Pathological images and neurokinin 1 receptor(NK-1R)expression of the skin were determined. Concentration of interleukin(IL)-31, IL-33, histamine, leukotriene B4, and SP was analyzed by enzyme-linked immunosorbent assay. Nitric oxide was analyzed by colorimetry. Results Transient pruritus induced by erlotinib appeared 2 to 5 days after treatment. In contrast, continuous pruritus was observed during the first hour, but was then gradually relieved. These two shared similar scratching behavior. Concentration of neurotransmitters showed similar trends in changes among the erlotinib group and SP group. Immunohistochemical expression was also consistent between the erlotinib group and SP group. Conclusions Erlotinib-associated pruritus is related to release of signaling factors through the SP/NK-1R signaling pathway.
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Background: Previous reports regarding the cutaneous adverse events of epidermal growth factor receptor inhibitors are mostly limited to small case reports and case series, mainly involving Caucasian patients. Aims: We describe the trends in the clinical presentation of Asian patients who had cutaneous adverse events induced by epidermal growth factor receptor inhibitors and to explore the relationship between skin adverse events and tumor response. Methods: From 2006 to 2010, medical records of Thai patients with non‑small cell lung cancer receiving epidermal growth factor receptor inhibitors were retrieved and analyzed. Results: In all, 99 patients were reviewed and analyzed. Erlotinib and gefitinib were commenced in 75 (75.8%) and 24 (24.2%) patients, respectively. Cutaneous adverse events occurred in 43 (57.3%) patients receiving erlotinib and in 15 (62.5%) patients receiving gefitinib. The most common adverse event was xerosis (52.5%). Less common adverse events included papulo-pustular eruption (27.3%), erythematous maculopapular rash (11.1%), mucositis (6.7%), paronychia (5.1%), and trichomegaly (2%). Elderly patients had a higher occurrence of xerosis. The presence of cutaneous adverse events was significantly higher in subjects who had a tumor response. Limitations: The limitations of study include its retrospective nature, and the initial screening of cutaneous adverse events was done by non‑dermatologists. Conclusions: Cutaneous adverse events due to epidermal growth factor receptor inhibitors are not uncommon in the Asian population. We found a positive correlation between the occurrences of cutaneou adverse events and tumor response supporting the view that they are surrogate markers for therapeutic response.
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The majority of patients with head and neck cancer present with locally advanced disease. Locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) poses one of the most complex management challenges. This stage of disease is still potentially curable, but requires combined-modality therapy. One of the novel approaches is the use of targeted agents, particularly the epidermal growth factor receptor (EGFR) inhibitors, in treatment strategies in LA-SCCHN. A Medline search covering topics related to targeted therapies in head and neck cancer over the last two decades was made and the facts were compiled. Cetuximab was the first novel agent to obtain regulatory approval in the United States for the treatment of patients with Head and Neck Squamous Cell Cancer HNSCC. Cetuximab has been evaluated in combination with radiotherapy, chemo-radiotherapy, and induction chemotherapies, and was found to increase the overall survival rates in all the arms without raising the toxicity level of the combined modality of treatment significantly. The tyrosine kinase inhibitors Gefinitib and Erlotinib also produced an average response rate of 11% and 4% in different studies and also prolonged the disease control rates when used with chemotherapy. This paper will review the role of targeted agents, particularly the EGFR inhibitors, in the present treatment strategies in advanced, recurrent/metastatic head and neck cancer.
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Epidermal growth factor receptor inhibitors (EGFRIs) are new anticancer agents that act by inhibiting EGFR signaling transduction pathways, thus decreasing tumor growth. They have made anti-cancer treatment more tolerable and have also reduced systemic side effects. However, they have many cutaneous side effects. Alopecia is an uncommon cutaneous side effect of EGFRIs, and cicatricial alopecia has been reported more rarely. A 59-year-old woman presented with itching and hair loss on the scalp, which started 2 months ago. She had been taking gefitinib for 7 months. A physical examination revealed localized erythematous hairless patches with scattered thick crusts on the scalp. Histopathologic examination showed a decreased number of hair follicles with perifollicular lymphocytes infiltration and perifollicular fibrosis, consistent with a scarring alopecia. We report a rare and interesting case of cicatricial alopecia after using the EGFRI, gefitinib.