A Randomized Phase II Study of Gefitinib Plus Simvastatin Versus Gefitinib Alone in Previously Treated Patients with Advanced Non―Small Cell Lung Cancer

• Published in: Clinical cancer research 2011-03, Vol.17 (6), p.1553-1560
• Main Authors: HAN, Ji-Youn, LEE, Soo-Hyun, NAM JIN YOO, SUK HYUNG LEE, YOON JOO MOON, YUN, Tak, HEUNG TAE KIM, JIN SOO LEE
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Disease-Free Survival; Humans; Lung Neoplasms - drug therapy; Medical sciences; Middle Aged; Mutation; Pharmacology. Drug treatments; Pneumology; Quinazolines - administration & dosage; Receptor, Epidermal Growth Factor - genetics; Simvastatin - administration & dosage; Treatment Outcome; Tumors of the respiratory system and mediastinum
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-10-2525

To evaluate the efficacy and safety of gefitinib plus simvastatin (GS) versus gefitinib alone (G) in previously treated patients with advanced non-small cell lung cancer (NSCLC). Between May 2006 and September 2008, 106 patients (51% men, 75% adenocarcinoma, 50% never smoker) were randomly assigned to G alone (250 mg/d, n = 54) or GS (250 and 40 mg/d, respectively, n = 52). One cycle was 4 weeks of treatment. Therapy was continued until disease progression or intolerable toxicity was observed. The primary endpoint was response rate (RR). Secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS). The RR was 38.5% (95% CI, 25.3-51.7) for GS and 31.5% (95% CI, 19.1-43.9) for G. The median PFS was 3.3 months [M] (95% CI, 1.4-5.2M) for GS and 1.9M (95% CI, 1.0-2.8M) for G. The median OS was 13.6M (95% CI, 7.1-20.1M) for GS and 12.0M (95% CI, 7.8-16.2M) for G. In exploratory subgroup analysis, GS showed higher RR (40% vs. 0%, P = 0.043) and longer PFS (3.6M vs. 1.7M, P = 0.027) compared with G alone in patients with wild-type epidermal growth factor receptor (EGFR) nonadenocarcinomas. Adverse events in both arms were generally mild and mainly consisted of skin rashes. Although no superiority of GS to G was demonstrated in this unselected NSCLC population, GS showed higher RR and longer PFS compared with G alone in patients with wild-type EGFR nonadenocarcinomas. Simvastatin may improve the efficacy of gefitinib in that subgroup of gefitinib-resistant NSCLC patients.