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Gefitinib Treatment (gefitinib + treatment)
Selected AbstractsEnhanced cytotoxicity induced by gefitinib and specific inhibitors of the Ras or phosphatidyl inositol-3 kinase pathways in non-small cell lung cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2006Maarten L. Janmaat Abstract In this study, we have characterized a panel of NSCLC cell lines with differential sensitivity to gefitinib for activating mutations in egfr, pik3ca, and k-ras, and basal protein expression levels of PTEN. The egfr mutant NSCLC cell line H1650 as well as the egfr wild type cell lines H292 and A431 were highly sensitive to gefitinib treatment, indicating that other factors determine gefitinib-sensitivity in egfr wild type cells. Activating k-ras mutations were specifically detected in gefitinib-resistant cells, suggesting that the occurrence of k-ras mutations is correlated with resistance to EGFR antagonists. No pik3ca mutations were detected within the panel of cell lines, and PTEN protein expression levels did not correlate with gefitinib sensitivity. Gefitinib effectively blocked Akt and Erk phosphorylation in two gefitinib-sensitive NSCLC cell lines, further supporting our previous findings that persistent activity of the PI3K/Akt and/or Ras/Erk pathways is associated with gefitinib-resistance of NSCLC cell lines. Gefitinib-resistant NSCLC cell lines, showing EGFR-independent activity of the PI3K/Akt or Ras/Erk pathways, were treated with gefitinib in combination with specific inhibitors of mTOR, P13K, Ras, and MEK. Additive cytotoxicity was observed in A549 cells co-treated with gefitinib and the MEK inhibitor U0126 or the farnesyl transferase inhibitor SCH66336 and in H460 cells treated with gefitinib and the PI3K inhibitor LY294002, but not in H460 cells treated with gefitinib and rapamycin. These data suggest that combination treatment of NSCLC cells with gefitinib and specific inhibitors of the PI3K/Akt and Ras/Erk pathways may provide a successful strategy. © 2005 Wiley-Liss, Inc. [source] Prognostic model to predict outcomes in nonsmall cell lung cancer patients treated with gefitinib as a salvage treatmentCANCER, Issue 7 2009Min Jae Park MD Abstract BACKGROUND: A prognostic model based on clinical parameters for nonsmall cell lung cancer (NSCLC) patients treated with gefitinib (250 mg/day) as a salvage therapy was devised. METHODS: Clinical data regarding a total of 316 metastatic or recurrent NSCLC patients who were treated with gefitinib were analyzed. RESULTS: Poor prognostic factors for overall survival (OS) by multivariate analysis were an Eastern Cooperative Oncology Group (ECOG) performance status of 2 to 3 (hazards ratio [HR] of 2.07; 95% confidence interval [CI], 1.57-2.73 [P < .001]), the presence of intra-abdominal metastasis (HR of 1.76; 95% CI, 1.33-2.34 [P < .001]), elevated serum alkaline phosphatase (HR of 1.50; 95% CI, 1.13-2.00 [P = .005]), time interval from diagnosis to gefitinib therapy of ,12 months (HR of 1.48; 95% CI, 1.12-1.95 [P = .005]), low serum albumin (HR of 1.45; 95% CI, 1.09-1.92 [P = .009]), progression-free interval for previous chemotherapy of ,12 weeks (HR of 1.40; 95% CI, 1.0-1.84 [P = .015]), white blood cell >10,000/,L (HR of 1.38; 95% CI, 1.02-1.85 [P = .032]), and ever-smoker (HR of 1.33; 95% CI, 1.02-1.75 [P = .033]). Of the 272 patients applicable to this prognostic model, 41 patients (15%) were categorized as a good prognosis group (0-1 risk factors), 100 patients (37%) as an intermediate prognosis group (2-3 risk factors), 81 patients (30%) as a poor prognosis group (4-5 risk factors), and 50 patients (16%) as a very poor prognosis group (,6 risk factors). The median OS from the time of gefitinib treatment for the good, intermediate, poor, and very poor prognosis groups were 18.0 months, 11.2 months, 4.0 months, and 1.3 months, respectively (P < .001). CONCLUSIONS: This prognostic model based on easily available clinical variables would be useful to identify patients who might derive more benefit from gefitinib treatment and to make decisions in clinical practice. Cancer 2009. © 2009 American Cancer Society. [source] Serum carcinoembryonic antigen level is associated with epidermal growth factor receptor mutations in recurrent lung adenocarcinomasCANCER, Issue 12 2007Fumihiro Shoji MD Abstract BACKGROUND. The presence of epidermal growth factor receptor (EGFR) gene mutations is a good indicator of the clinical efficacy of gefitinib in patients with nonsmall cell lung cancer. It was recently reported that the serum carcinoembryonic antigen (CEA) level could be a predictive factor for the efficacy of gefitinib treatment; therefore, it is suggested that the EGFR gene mutation is associated with the serum CEA level. The current study analyzed the association between EGFR gene mutations and clinical features, including the serum CEA level, in patients with recurrent lung adenocarcinomas. METHODS. A total of 48 lung adenocarcinoma patients with postoperative disease recurrence who underwent chemotherapy were investigated. EGFR gene mutations at exons 18, 19, and 21 were measured using surgical specimens taken from the primary tumor. RESULTS. Mutations of the EGFR gene were detected in 25 of the 48 patients and the abnormal serum CEA concentration at the time of disease recurrence was found to be significantly associated with the incidence of EGFR gene mutations (P = .045). The rate of EGFR gene mutations significantly increased as the serum CEA level increased (serum CEA level; <5 vs ,5 <20 vs ,20 = 35% vs 55% vs 87.5%, respectively, P = .040). A multivariate analysis revealed that a higher serum CEA level at the time of disease recurrence is independently associated with EGFR gene mutations (P = .036) with an odds ratio of 4.70 (95% confidence interval, 1.1,21.1). CONCLUSIONS. The serum CEA level appears to be closely associated with the presence of EGFR gene mutations in patients with pulmonary adenocarcinomas. Cancer 2007. © 2007 American Cancer Society. [source] Phase II randomized study of daily gefitinib treatment alone or with vinorelbine every 2 weeks in patients with adenocarcinoma of the lung who failed at least 2 regimens of chemotherapyCANCER, Issue 9 2007Yuh-Min Chen MD Abstract BACKGROUND. The objective of this study was to assess the efficacy of adding chronic, intermittent, low-dose vinorelbine to gefitinib treatment for patients who had adenocarcinoma of the lung who failed ,2 regimens of chemotherapy. METHODS. Patients were randomized into 2 arms: Oral gefitinib 250 mg daily (the G arm) or vinorelbine 15 mg/m2 as an intravenous infusion on Day 1 and oral gefitinib 250 mg daily on Days 2 through 14 every 2 weeks (the GV arm). From August 2004 to October 2005, 48 patients were enrolled. Epidermal growth factor receptor (EGFR) exon 18 through 21 nucleotide sequence analysis and fluorescence in situ hybridization were performed in patients who had tumor tissue specimens available for analysis. RESULTS. After randomization, each arm had 24 patients. However, 3 patients refused vinorelbine treatment and were given gefitinib treatment only. Thus, 27 patients received G treatment, and 21 patients received GV treatment. Objective response rates were 55.6% in the G arm and 52.4% in the GV arm. All toxicities in both arms were mild. The 1-year progression-free survival rate was 57.1% in the GV arm and 21.2% in the G arm (P = .008). The median survival was 13.3 months in the G arm and 23.4 months in the GV arm (P = .1231). Three of 6 patients (50%) had an exon 19 in-frame deletion, and 2 of 10 patients had EGFR gene high polysomy or amplification (20%). CONCLUSIONS. Gefitinib was highly effective in ethnic Chinese patients with adenocarcinoma of the lung who failed previous platinum and taxane treatment. The addition of low-dose vinorelbine every 2 weeks produced a significantly better 1-year progression-free survival rate. Cancer 2007. © 2007 American Cancer Society. [source] | ||||||||||