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Carcinoma, Bronchogenic

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Lung Diseases

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Small Cell Lung Cancer

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Lipid Regulating Agents

Irinotecan

Simvastatin

Cisplatin

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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

IP chemotherapy

* 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

IP chemotherapy plus simvastatin

JI-YOUN HAN, M.D. PhD.

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.

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.

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

Survival time will be calculated from the date of study treatment start to the date of death.( or date last seen ) Follow - up visits are conducted every 8 weeks to obtain meaningful data on time- to event variables. Assessment will continue until death or 12 months after treatment.

The response rate will be determined by the number of patients with complete and partial responses according to RECIST criteria 1.1

Progression free survival will be calculated from the date of study treatment start to the first objective documentation of progressive disease or to the date of death, whichever occurs first.

Safety will be evaluated by the frequency, severity, and relationship of adverse event graded by NCI Common Toxicity Criteria version 4.0 that occur during the treatment and follow up periods.

National Cancer Center, Korea

Head, lung cancer center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Irinotecan/Cisplatin With or Without Simvastatin in Chemo-naive Patients With Extensive Disease-small Cell Lung Cancer	NCT01441349	Small Cell Lung...	IP chemotherapy IP chemotherapy...	18 Years -	National Cancer Center, Korea
Irinotecan/Cisplatin With or Without Simvastatin in Chemo-naive Patients With Extensive Disease-small Cell Lung Cancer	NCT01441349	Small Cell Lung...	IP chemotherapy IP chemotherapy...	18 Years -	National Cancer Center, Korea

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