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

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 ¼ 54) or GS (250 and 40 mg/d, respectively, n ¼ 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 ¼ 0.043) and longer PFS (3.6M vs.

Use of the Epidermal Growth Factor Receptor Inhibitors Gefitinib, Erlotinib, Afatinib, Dacomitinib, and Icotinib in the Treatment of Non-Small-Cell Lung Cancer: A Systematic Review

“…A number of trials demonstrated improved pfs for the combination of an egfr inhibitor and a targeted agent. However, none of the trials demonstrated any statistically significant improvements in os 74 . Despite the heterogeneous nature of the trials, it is reasonable to conclude that no available evidence currently supports the combination of erlotinib with another targeted agent.…”

Statin Use and Survival from Lung Cancer: A Population-Based Cohort Study

“…Our study also found no association between pravastatin use after diagnosis and cancer-specific mortality (adjusted HR, 1.23; 95% CI, 0.85-1.77; P ¼ 0.27), but we found some evidence of protective associations for other statins that were not investigated in this trial, such as simvastatin. A similar phase II trial (26) has also been conducted that included 106 advanced (stage IIIb or IV) non-small cell lung cancer patients. This trial observed a weak improvement in survival in a group that received simvastatin plus gefitinib compared with gefitinib only (HR, 0.88; 95% CI, 0.57-1.35: P ¼ 0.49), but this was not significant.…”

Simvastatin sensitizes human gastric cancer xenograft in nude mice to capecitabine by suppressing nuclear factor-kappa B-regulated gene products

“…Simvastatin has been used in combination therapy with several chemotherapeutic agents/targeted therapies such as farnesyl transferase inhibitors, EGFR inhibitors geftinib and cetuximab, doxorubicin, non-steroidal anti-inflammatory drugs, and vitamin-E gamma tocotrienol in diverse tumor cell lines and in vivo cancer models [10,13,16,[32][33][34] but so far its effects either alone or in combination with anticancer therapies in gastric cancer mouse models has never been studied before. Recently conducted couple of populationbased case-control studies clearly indicate that statins uptake can reduce the risk of gastric cancer [35], and our findings provide further scientific evidence that simvastatin has significant potential for the treatment of gastric cancer and its effects can be further enhanced by capecitabine.…”