Han, Ji-Youn; Lee, Soo-Hyun; Yoo, Nam Jin; Hyung, Lee Suk; Moon, Yoon Joo; Yun, Tak; Kim, Heung Tae; Lee, Jin Soo
Clinical cancer research : an official journal of the American Association for Cancer Research
2011Mar ; 17 ( 6 ) :1553-60.
PMID : 21411446
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Han, Ji-Youn -
Lee, Soo-Hyun -
Yoo, Nam Jin -
Hyung, Lee Suk -
Moon, Yoon Joo -
Yun, Tak -
Kim, Heung Tae -
Lee, Jin Soo -
ABSTRACT
PURPOSE: 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). EXPERIMENTAL DESIGN: 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).
RESULTS: 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.
CONCLUSIONS: 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. CI - ??011 AACR.
Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use; Carcinoma, Non-Small-Cell Lung/*drug therapy; Disease-Free Survival; Humans; Lung Neoplasms/*drug therapy; Middle Aged; *Mutation; Quinazolines/*administration & dosage; Receptor, Epidermal Growth Factor/*genetics; Simvastatin/*administration & dosage; Treatment Outcome
MESH
Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, Carcinoma, Non-Small-Cell Lung/*drug therapy, Disease-Free Survival, Humans, Lung Neoplasms/*drug therapy, Middle Aged, *Mutation, Quinazolines/*administration & dosage, Receptor, Epidermal Growth Factor/*genetics, Simvastatin/*administration & dosage, Treatment Outcome
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