Cancer Res Treat.  2023 Jul;55(3):885-893. 10.4143/crt.2023.283.

A Randomized Phase II Study of Irinotecan Plus Cisplatin with or without Simvastatin in Ever-Smokers with Extended Disease Small Cell Lung Cancer

• Lee Y
• Lee SH
• Lee GK
• Lim EJ
• Han JY

• KMID: 2544169
• DOI: http://doi.org/10.4143/crt.2023.283

Abstract

Purpose
This study evaluated whether an addition of simvastatin to chemotherapy improves survival in ever-smokers with extensive disease (ED)–small cell lung cancer (SCLC).
Materials and Methods
This is an open-label randomized phase II study conducted in National Cancer Center (Goyang, Korea). Chemonaive patients with ED-SCLC, smoking history (≥ 100 cigarettes lifetime), and Eastern Cooperative Oncology Group performance status of ≤ 2 were eligible. Patients were randomized to receive irinotecan plus cisplatin alone or with simvastatin (40 mg once daily orally) for a maximum of six cycles. Primary endpoint was the the 1-year survival rate.
Results
Between September 16, 2011, and September 9, 2021, 125 patients were randomly assigned to the simvastatin (n=62) or control (n=63) groups. The median smoking pack year was 40 years. There was no significant difference in the 1-year survival rate between the simvastatin and control groups (53.2% vs. 58.7%, p=0.535). The median progression-free survival and overall survival between the simvastatin arm vs. the control groups were 6.3 months vs. 6.4 months (p=0.686), and 14.4 months vs. 15.2 months, respectively (p=0.749). The incidence of grade 3-4 adverse events was 62.9% in the simvastatin group and 61.9% in the control group. In the exploratory analysis of lipid profiles, patients with hypertriglyceridemia had significantly higher 1-year survival rates than those with normal triglyceride levels (80.0% vs. 52.7%, p=0.046).
Conclusion
Addition of simvastatin to chemotherapy provided no survival benefit in ever-smokers with ED-SCLC. Hypertriglyceridemia may be associated with better prognosis in these patient population.

Keyword

Small cell lung carcinoma; Statin; Smokers; Triglycerides; Irinotecan

Figure

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  Fig. 1 Consolidated Standards of Reporting Trials (CONSORT) study diagram.

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  Fig. 2 Kaplan-Meier curves: progression-free survival (PFS) (A) and overall survival (OS) (B). CI, confidence interval; HR, hazard ratio; IP, irinotecan plus cisplatin; IP-sim, irinotecan plus cisplatin and simvastatin.

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  Fig. 3 1-Year survival rate analysis by clinical factors and lipid and lipoprotein levels. BMI, body mass index; ECOG PS, Eastern Cooperative Oncology Group performance status; HDL-C, high-density lipoprotein–cholesterol; LDH, lactate dehydrogenase; LDL-C, low-density lipoprotein–cholesterol; OS, overall survival; TG, triglyceride.

Reference

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