Intermittent Chemotherapy and Erlotinib for Nonsmokers or Light Smokers with Advanced Adenocarcinoma of the Lung: A Phase II Clinical Trial (original) (raw)
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Cancer Biology & Therapy, 2016
Among attempts to delay development of resistance to tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) with activating mutations of epidermal growth factor receptor (EGFR), intercalated therapy has not been properly evaluated. In a phase II trial, 38 patients with EGFR mutated NSCLC in advanced stage were treated with 4 to 6 3-weekly cycles of intercalated schedule with gemcitabine (1250 mg/m2, days 1 and 4), cisplatin (75 mg/m2, day 2) and erlotinib (150 mg, days 5-15), followed by continuous erlotinib as maintenance. In addition to standard radiologic evaluation according to RECIST, PET/CT was done prior to treatment and at 6 months, using PERCIST as a method for assessment of response. The primary endpoint was progression-free survival (PFS). In general, tolerance to treatment was good, even among 8 patients with performance status 2-3 and 13 patients with brain metastases; grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. Complete response (CR) or partial response (PR) were seen in 15 (39.5%) and 17 (44.7%) cases, respectively. All cases of CR were confirmed also by PET/CT. Median PFS was 23.4 months and median overall survival (OS) was 38.3 months. After a median follow-up of 35 months, 8 patients are still in CR and on maintenance erlotinib. In conclusion, intercalated treatment for treatment-naive patients with EGFR activating mutations leads to excellent response rate and prolonged PFS and survival. Comparison of the intercalated schedule to monotherapy with TKIs in a randomized trial is warranted.
OncoTargets and Therapy
This paper presents a rare case of an elderly patient treated with erlotinib for disseminated lung adenocarcinoma with poor performance status (Eastern Cooperative Oncology Group performance status [PS]3). This treatment led to a long duration of complete remission according to Response Evaluation Criteria in Solid Tumors 1.1-almost 7 years (81 months) of progression-free survival (PFS) and overall survival (OS) of 10 years by March 2017. The treatment with erlotinib started in September 2008 and it was well tolerated with no adverse effects. Mutation analyses (real-time polymerase chain reaction method) revealed deletion of EGFR (epidermal growth factor receptor) gene and wild-type Kirsten-ras protein gene in exon 19. In May 2015, the patient relapsed with jaundice and enlarged lymph nodes of the liver hilum, with no other metastasis, PS 2. Biopsy confirmed metastasis of lung adenocarcinoma. EGFR molecular testing did not reveal T790M mutation. Treatment was continued with gemcitabinecisplatin chemotherapy. A total of six cycles were administered with nearly complete response and Eastern Cooperative Oncology Group performance status 0. Further on, gemcitabine monotherapy has been administered with nearly complete response maintained and OS of 10 years by March 2017. This report describes an extremely rare case of a poor performance patient with advanced metastatic adenocarcinoma harboring EGFR mutation-deletion in exon 19-who was receiving salvage erlotinib and had a complete response with 81 months of PFS followed by a relapse and subsequent chemotherapy which led to nearly complete response, with an OS of 10 years by March 2017. Such a complete response to tyrosine kinase inhibitor therapy in a poor PS patient, with long PFS and OS achieved, justifies tyrosine kinase inhibitor treatment approach in poor PS patients with EGFR-sensitizing tumors, and furthermore points to the feasibility of administering chemotherapy at the time of relapse.
The Lancet Oncology, 2010
Background First-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) is usually limited to four to six cycles. Maintenance therapy can delay progression and prolong survival. The oral epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor erlotinib has proven effi cacy and tolerability in second-line NSCLC. We designed the phase 3, placebo-controlled Sequential Tarceva in Unresectable NSCLC (SATURN; BO18192) study to assess use of erlotinib as maintenance therapy in patients with non-progressive disease following fi rst-line platinumdoublet chemotherapy.
Impact of active smoking on patients with metastatic lung adenocarcinoma harboring an EGFR mutation
Lung cancer in smokers and non-smokers demonstrates distinct genetic profiles, and cigarette smoking affects epidermal growth factor receptor (EGFR) function and causes secondary EGFR tyrosine kinase resistance. We evaluated the effect of active smoking in patients with metastatic lung adenocarcinoma. A total of 132 metastatic lung adenocarcinoma patients, diagnosed between 2008 and 2013, with known EGFR mutation status, were evaluated retrospectively. Among these patients, 40 had an activating EGFR mutation. Patients who continued smoking during the treatment were defined as active smokers. Former smokers and never smokers were together defined as non-smokers. The outcomes of the treatment in relation to the EGFR mutation and smoking status were evaluated. The median follow-up time was 10.5 months. The overall response rate for the first-line therapy was significantly higher among the EGFR-mutant patients (p = 0.01), however, smoking status had no impact on the response rate (p = 0.1). The EGFR-mutant active smokers progressed earlier than the non-smokers (p < 0.01). The overall survival (OS) of the non-smokers and patients treated with erlotinib was significantly longer (p = 0.02 and p = 0.01, respectively). Smoking status did not affect the OS in EGFR wild type tumors (p = 0.49) but EGFR-mutant non-smokers had a longer OS than the active smokers (p = 0.01). The active smokers treated with erlotinib had poorer survival than the non-smokers (p = 0.03). Multivariate analysis of EGFR-mutant patients showed that erlotinib treatment at any line and non-smoking were independent prognostic factors for the OS (p = 0.04 and p = 0.01, respectively). Smoking during treatment is a negative prognostic factor in metastatic lung adenocarcinoma with an EGFR mutation.
Open Access Macedonian Journal of Medical Sciences
Background: EGFR mutation is a genetic disorder that is often observed and examined in Non-Small Cell Lung Carcinoma. EGFR mutation detection aims to predict sensitivity to EGFR-TKI and acts as first-line therapy. Targeted therapy with EGFR-TKI can increase the survival rate of patients with Non-Small Cell Lung Cancer compared to chemotherapy. This study aims to obtain data on the survival rate of patients with Non-Small Cell Lung Carcinoma who received targeted therapy at H. Adam Malik Hospital. Methods: This study is a descriptive study with a retrospective cohort design carried out at the Oncology Polyclinic at RSUP H Adam Malik Medan for 5 years, from January 2014 to December 2018. The subjects of this study were all patients with lung cancer type adenocarcinoma who had received therapy with generation 1 or 2 EGFR TKI. Results: 99 patients were included as subjects of this study. From the study, the most influential factors on lung cancer were gender, age, and smoking addictio...
Radiology and Oncology, 2014
Background. Pharmaco-dynamic separation of cytotoxic and targeted drugs might avoid their mutual antagonistic effect in the treatment of advanced non-small cell lung cancer (NSCLC). Patients and methods. Eligible patients were treatment-naive with stage IIIB or IV NSCLC. In addition, inclusion was limited to never-smokers or light smokers or, after 2010, to patients with activating epidermal growth-factor receptor (EGFR) mutations. Treatment started with 3-weekly cycles of gemcitabine and cisplatin on days 1, 2 and 4 and erlotinib on days 5 to 15. After 4 to 6 cycles, patients continued with erlotinib maintenance. Results. Fifty-three patients were recruited into the trial: 24 prior to 2010 (of whom 9 were later found to be positive for EGFR mutations), and 29 EGFR mutation-positive patients recruited later. Unfavourable prognostic factors included stage IV disease (51 patients - 96%), performance status 2-3 (11 patients - 21%) and brain metastases (15 patients - 28%). Grade 4 toxic...
Advanced lung adenocarcinoma in an EGFR-positive patient treated with Erlotinib for 52 months
Respiratory Medicine Case Reports, 2013
The authors present a case of a 53-years-old non-smoker Caucasian female who was diagnosed with lung adenocarcinoma (stage IA) and underwent surgical resection in 2002. Five years later, the tumor relapsed (stage IV disease) and she initiated chemotherapy with carboplatin, gemcitabine and bevacizumab as a first-line therapy. Despite partial remission after four cycles, this regimen was discontinued due to unacceptable toxicity. In 2008, the disease progressed and the patient was started on Erlotinib as secondline treatment. The patient had a sustained partial remission which she maintains at present e 52 months after initiation of Erlotinib. Molecular testing performed on the primary lung tumor revealed an Epidermal Growth Factor Receptor (EGFR) gene mutation (deletion in exon 19).
Bosnian Journal of Basic Medical Sciences, 2016
Lung cancer in smokers and non-smokers demonstrates distinct genetic profiles, and cigarette smoking affects epidermal growth factor receptor (EGFR) function and causes secondary EGFR tyrosine kinase resistance. We evaluated the effect of active smoking in patients with metastatic lung adenocarcinoma. A total of 132 metastatic lung adenocarcinoma patients, diagnosed between 2008 and 2013, with known EGFR mutation status, were evaluated retrospectively. Among these patients, 40 had an activating EGFR mutation. Patients who continued smoking during the treatment were defined as active smokers. Former smokers and never smokers were together defined as non-smokers. The outcomes of the treatment in relation to the EGFR mutation and smoking status were evaluated. The median follow-up time was 10.5 months. The overall response rate for the first-line therapy was significantly higher among the EGFR-mutant patients (p = 0.01), however, smoking status had no impact on the response rate (p = 0.1). The EGFR-mutant active smokers progressed earlier than the non-smokers (p < 0.01). The overall survival (OS) of the non-smokers and patients treated with erlotinib was significantly longer (p = 0.02 and p = 0.01, respectively). Smoking status did not affect the OS in EGFR wild type tumors (p = 0.49) but EGFR-mutant non-smokers had a longer OS than the active smokers (p = 0.01). The active smokers treated with erlotinib had poorer survival than the non-smokers (p = 0.03). Multivariate analysis of EGFR-mutant patients showed that erlotinib treatment at any line and non-smoking were independent prognostic factors for the OS (p = 0.04 and p = 0.01, respectively). Smoking during treatment is a negative prognostic factor in metastatic lung adenocarcinoma with an EGFR mutation.
Jurnal Kedokteran Brawijaya
Globally, lung cancer is by far the leading cause of death by cancer-which contribute to 2.094 million death-with the highest toll from cancer being 1.8 million. Currently, lung cancer therapy has developed from chemotherapy to targeted therapy, such as Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI). This study aimed to assess the survival rate of adenocarcinoma cell lung cancer patients who received EGFR-TKI therapy at the Pulmonary Clinic of Dr. Saiful Anwar General Hospital Malang. This study was a retrospective study using patient medical records between 2017 and 2020. The data were processed and analyzed using the Chi-Square test. The number of samples was 117 patients consisting of 63 patients receiving Gefitinib therapy, 36 patients receiving Afatinib therapy, and 18 patients receiving Erlotinib therapy. There were no significant differences between variables of age, sex, smoking history, stage, and exon mutations with 1-year survival. Gefitinib therapy...