NCT01441349

Irinotecan/Cisplatin With or Without Simvastatin in Chemo-naive Patients With Extensive Disease-small Cell Lung Cancer

A Randomized Phase II Study of Irinotecan/Cisplatin With or Without Simvastatin in Chemo-naive Patients With Extensive Disease-small Cell Lung Cancer

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 192 (estimated)
• Sponsor: National Cancer Center, Korea · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to compare the efficacy of Simvastatin and Irinotecan/Cisplatin chemotherapy with Irinotecan/Cisplatin chemotherapy alone in Extensive disease-small cell lung cancer.

Detailed description

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been used to treat hypercholesterolemia. Besides the lipid lowering effects, they also act as anti-inflammatory and anti-cancer agents. Recently the investigators demonstrated a synergistic cytotoxicity between Simvastatin and Irinotecan in human lung cancer cells. Simvastatin enhances Irinotecan-induced apoptosis by inhibition of proteasome activity. All of these additional actions may counteract harmful effects of smoking-induced chronic inflammation. These properties together with a high safety profile have made Statins more attractive drug for small cell lung cancer (SCLC), the highly smoking-related cancer. Given the promising preclinical anti-tumor and anti-inflammatory effects of Simvastatin in SCLC, recently the investigators conducted a phase II study of Simvastatin and Irinotecan/Cisplatin (IP) chemotherapy in chemo-naïve- patients with Extensive disease-small cell lung cancer (ED-SCLC). The 1-year survival rate was 39.3%. The median overall survival (OS) and progression free survival (PFS) was 11.0 months and 6.1 months, respectively. Overall relative risk (RR) was 75%. The most common toxicity was neutropenia (67%). The efficacy was significantly associated with smoking-status. Compared with never-smokers, ever-smokers had higher RR (40% v 78%, P=0.01) and longer PFS (2.5 months v 6.4 months, P=0.018) and showed a trend toward improved OS (9.0 months v 11.2 months, P=0.095). The effect of smoking on survival was apparent when subdividing ever smokers according to pack-years (PY). Ever-smokers who smoked \> 65 PY showed significantly longer OS compared to ever-smokers who smoked \<= 65 PY or never-smokers (20.6 months v 10.6 months v 9.0 months, log-rank P=0.032). In multivariate analysis, PY \> 65 was predictive for longer survival (hazard ratio) HR=0.377 \[95% CI (confidence interval), 0.157-0.905\]). These findings suggest that the addition of Simvastatin to Irinotecan and Cisplatin improved efficacy in ever-smokers with ED-SCLC. The survival benefit of this combination seems apparent in heavy-smokers.

Conditions

• Small Cell Lung Carcinoma

Interventions

Type	Name	Description
DRUG	IP chemotherapy	Irinotecan/cisplatin (IP) chemotherapy * Cisplatin(30 mg/m2) diluted into 150 ml of 0.9% NS for IV over 30 min on day 1 \&8. * Irinotecan(65mg/m2) diluted into 200ml of 5DW IV over 90 min on day 1 \& 8 * Every 21 days
DRUG	IP chemotherapy plus simvastatin	* Cisplatin(30mg/m2)diluted into 150 ml of 0.9% NS for IV over 30 min on day 1 \&8 * Irinotecan( 65 mg/m2) diluted into 200ml of 5DW IV over 90 min on day 1\& 8. * Every 21days. * Simvastatin 40 mg per day orally D1of cycle 1

Timeline

• Start date: 2011-08-01
• Primary completion: 2022-10-31
• Completion: 2022-12-31
• First posted: 2011-09-27
• Last updated: 2022-04-06

Locations

1 site across 1 country: South Korea