250 IRESSA Film-Coated Tablets 250 mg 023808 IRESSA 250 250mg gefitinib IRESSA IRESSA 250mg ( ) ( 10 ) IRESSA 14 250mg
Iressa (ILD) / / / / Iressa Iressa 3159 Iressa 12 (ILD) Iressa PS 2 50% 6 55 IRESSA CYP3A4 gefitinib CYP3A4 phenytoin carbamazepine rifampicin St John s warfarin (INR) / warfarin (PT) INR ph gefitinib
IRESSA brain stem glioma incompletely resected supratentorial malignant glioma 45 4 1 ependymoma IRESSA IRESSA IRESSA vinorelbine IRESSA vinorelbine gefitinib CYP3A4 rifampicin( 3A4 ) gefitinib AUC rifampicin 83% itraconazole CYP3A4 gefitinib AUC 80% ph 5 gefitinib AUC 47% IRESSA gefitinib IRESSA
IRESSA 20% 8% ADR (Common Toxicity Criteria CTC) 3 4 3% ADR ADR (>10%) CTC 1 2 CTC 3 4 CTC 1 CTC 1 2 (>1-10%) CTC 1 2 CTC 1 CTC 1 2 CTC 1 CTC 1 2 CTC 1 * CTC 1
(>0.1-1%) (>0.01-1%) warfarin (INR) / (CTC 3-4 ) (< 1%) Stevens Johnson syndrome * IRESSA expanded access / compassionate use ILD 0.3% phase III 1692 IRESSA BSC 1 2 ILD 1% ILD IRESSA IRESSA ILD 3% 4% 3350 ILD IRESSA 5.8% 12 ILD Iressa 4.0% 2.1% Iressa ILD OR 3.2 95% CI 1.9 5.4
Iressa ILD 3.8 95% CI 1.9 7.7 2.5 95% CI 1.1 5.8 IRESSA 1000mg Gefitinib (epidermal growth factor receptor EGFR) (tyrosine kinase) EGFR gefitinib IRESSA phase II NSCLC IRESSA phase III IRESSA 1 2 IRESSA HR 0.89, CI 0.77-1.02, p=0.09, gefitinib 5.6 5.1 HR 0.84, CI 0.68-1.03, p=0.09, gefitinib 6.3 5.4 IRESSA IRESSA HR=0.66, CI 0.48-0.91, p=0.01, 9.5 5.5 HR=0.67, CI 0.49-0.92, p=0.01, 8.9 6.1 EGFR gene copy number IRESSA gene copy number gene
copy number interaction p-value=0.0448 gene copy number IRESSA 0.61 N=114, 95% CI 0.36-1.04, p=0.067 gene copy number 1.16 N=256, 95% CI 0.81-1.64, p=0.42 EGFR gene copy number N=1322, HR=0.85, CI 0.73-0.99, p=0.032 EGFR gene copy number fluorescence in situ hybridisation LSI EGFR SpetrumOrange / CEP 7 SpetrumGreen probe 40% 4 copies EGFR / 2 10% EGFR 15 copies EGFR IRESSA EGFR N=264, HR=0.77; CI 0.56-1.08, p=0.13 EGFR N=115, HR=1.57; CI 0.86-2.87, p=0.14 EGFR EGFR N=1313, HR=0.84; CI 0.73-0.98, p=0.03 HR EGFR DAKO pharmdx TM EGFR EGFR pharmdx TM 1% 10% EGFR EGFR IRESSA EGFR gene copy number IRESSA EGFR gene copy numberegrf gefitinib 48 41 Gefitinib 1 2-8 7-10 24 2-3
IRESSA gefitinib 3-7 59% gefitinib (exposure) 5 gefitinib 47% gefitinib 1400L 90% Gefitinib 1- P450 CYP3A4 gefitinib gefitinib CYP2D6 gefitinib metoprolol CYP2D6 metoprolol (35%) Gefitinib P450 Gefitinib N-propylmorpholino quinazoline O-desmethyl gefitinib 14% 8 o-desmethyl gefitinib EGFR gefitinib 14 gefitinib O-desmethyl gefitinib CYP2D6 CYP2D6 CYP2D6 gefitinib O-desmethyl gefitinib Gefitinib
gefitinib CYP2D6 Gefitinib 500 / 4% phase I open-label gefitinib 250mg Child-Pugh 3.1 gefitinib gefitinib Gefitinib 41 250mg IRESSA Cmaxss AUC24ss 4 Gefitinib gefitinib 20mg 30mg 20mg 20mg 14-14 gefitinib
gefitinib QT rat 10mg/kg/day mice 50mg/kg/day 90mg/kg/day 22 125mg/kg/day 30 2007 4 AstraZeneca AstraZeneca UK Limited Silk Road, Business Park, Macclesfield, Cheshire, SK10 2NA England
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