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

National Cancer Center (NCC)

Status and phase

Unknown

Phase 2

Conditions

Small Cell Lung Carcinoma

Treatments

Drug: IP chemotherapy plus simvastatin

Drug: IP chemotherapy

Study type

Interventional

Funder types

Other

Identifiers

NCT01441349

NCCCTS-11-527

Details and patient eligibility

About

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.

Full 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.

Enrollment

192 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically confirmed SCLC
Extensive - stage disease, defined as disease extending beyond one hemithorax or involving contralateral mediastinal, hilar or supraclavicular lymph nodes, and/ or pleural effusion
ever smoker( have smoked> 100 cigarettes in entire lifetime
No prior chemotherapy, immunotherapy, or radiotherapy
Measurable disease according to RECIST 1.1
Patient compliance that allow adequate follow - up
Adequate hematologic , hepatic and renal function.
Written informed consent that is consistent with International Conference on Harmonization (ICH) - Good Clinical Practice (GCP) guidelines
Males of females at least 18 years of age
If female : childbearing potential either terminated by surgery, radiation, or menopause or attenuated by use of an approved contraceptive method(intrauterine device, birth control pills, or barrier device)during for 3 months after trial. If male, use of an approved contraceptive method during the study and 3 months afterwards. Females with childbearing potential must have a urine negative hCG test within 7 days prior to the study enrollment.
No concomitant prescriptions including cyclosporin A, valproic acid, phenobarbital, phenytoin, ketoconazole.
Patients with brain metastasis are allowed unless there were clinically significant neurological symptoms or signs.

Exclusion criteria

Inability to comply with protocol or study procedures.
A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study.
A serious cardiac condition, such as myocardial infarction with 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV.
Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
Concurrent administration of any other antitumor therapy.
Pregnant or Breast-feeding.
Taking simvastatin or Any contraindications for therapy with simvastatin