BACKGROUND: Brain metastases are a common occurrence in patients with non-small-cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT) is the standard therapy; more aggressive approaches such as surgery or radiosurgery are indicated in a subset of patients only. The role of systemic treatments remains controversial. Gefitinib is an oral, highly tolerable, specific inhibitor of epidermal growth factor receptor-associated tyrosine kinase, which has shown activity in chemotherapy pre-treated NSCLC. The aim of this study was to evaluate the activity and safety of gefitinib in NSCLC patients with brain metastases. PATIENTS AND METHODS: From January 2001 to May 2003, 41 consecutive NSCLC patients with measurable brain metastases were treated with gefitinib, given orally at daily dose of 250 mg. Thirty-seven patients had received previous chemotherapy and 18 patients had been treated previously with WBRT, completed at least 3 months before entering the trial. RESULTS: A partial response (PR) was observed in four patients (10%), with stable disease (SD) in seven cases, for an overall disease control (DC) rate (DC=PR+SD) of 27% (95% confidence interval 13% to 40%). Median duration of PR was 13.5 months. Median progression-free survival (PFS) of the whole population was 3 months. DC rate was higher in patients pre-treated with WBRT (P=0.05) and with adenocarcinoma histological type (P=0.08); adenocarcinoma patients had also a longer PFS (P=0.04). Toxicity was mild and consisted of grade 1/2 skin toxicity and diarrhoea, occurring in 24% and 10% of patients, respectively. CONCLUSIONS: Gefitinib can be active on brain disease in NSCLC patients. Since the results of standard therapy for brain metastases in this clinical setting are particularly disappointing, gefitinib appears to be a possible new treatment option.
BACKGROUND:Brain metastases are a common occurrence in patients with non-small-cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT) is the standard therapy; more aggressive approaches such as surgery or radiosurgery are indicated in a subset of patients only. The role of systemic treatments remains controversial. Gefitinib is an oral, highly tolerable, specific inhibitor of epidermal growth factor receptor-associated tyrosine kinase, which has shown activity in chemotherapy pre-treated NSCLC. The aim of this study was to evaluate the activity and safety of gefitinib in NSCLCpatients with brain metastases. PATIENTS AND METHODS: From January 2001 to May 2003, 41 consecutive NSCLCpatients with measurable brain metastases were treated with gefitinib, given orally at daily dose of 250 mg. Thirty-seven patients had received previous chemotherapy and 18 patients had been treated previously with WBRT, completed at least 3 months before entering the trial. RESULTS: A partial response (PR) was observed in four patients (10%), with stable disease (SD) in seven cases, for an overall disease control (DC) rate (DC=PR+SD) of 27% (95% confidence interval 13% to 40%). Median duration of PR was 13.5 months. Median progression-free survival (PFS) of the whole population was 3 months. DC rate was higher in patients pre-treated with WBRT (P=0.05) and with adenocarcinoma histological type (P=0.08); adenocarcinomapatients had also a longer PFS (P=0.04). Toxicity was mild and consisted of grade 1/2 skin toxicity and diarrhoea, occurring in 24% and 10% of patients, respectively. CONCLUSIONS:Gefitinib can be active on brain disease in NSCLCpatients. Since the results of standard therapy for brain metastases in this clinical setting are particularly disappointing, gefitinib appears to be a possible new treatment option.
Authors: Stephanie Heon; Beow Y Yeap; Gregory J Britt; Daniel B Costa; Michael S Rabin; David M Jackman; Bruce E Johnson Journal: Clin Cancer Res Date: 2010-10-28 Impact factor: 12.531
Authors: Tony J C Wang; Shumaila Saad; Yasir H Qureshi; Ashish Jani; Tavish Nanda; Andrew M Yaeh; Tzlil Rozenblat; Michael B Sisti; Jeffrey N Bruce; Guy M McKhann; Jeraldine Lesser; Balazs Halmos; Mark B Stoopler; Andrew B Lassman; Simon K Cheng; Steven R Isaacson Journal: Neuro Oncol Date: 2015-04-24 Impact factor: 12.300
Authors: Minjee Kim; Janice K Laramy; Afroz S Mohammad; Surabhi Talele; James Fisher; Jann N Sarkaria; William F Elmquist Journal: Drug Metab Dispos Date: 2019-01-31 Impact factor: 3.922