title: A phase 2 study of irinotecan, cisplatin, and simvastatin for untreated extensive-disease small cell lung cancer.
abstract: BACKGROUND
  The objective of this study was to investigate the efficacy of simvastatin in combination with irinotecan and cisplatin in chemotherapy-naive patients with extensive-disease small-cell lung cancer (ED-SCLC).
  
  
  METHODS
  In this phase 2 study, 61 patients received treatment with irinotecan (65 mg/m(2) ) and cisplatin (30 mg/m(2) ) on Days 1 and 8 every 3 weeks until either death or disease progression occurred. Patients also received oral simvastatin (40 mg daily) during the course of chemotherapy. The primary endpoint was 1-year survival. Secondary endpoints included the response rate (RR), progression-free survival (PFS), and toxicity.
  
  
  RESULTS
  The 1-year survival rate was 39.3%. The median overall survival (OS) was 11 months, and the median PFS was 6.1 months. Overall, the RR was 75%. The most common grade 3/4 toxicity was neutropenia (67%). Efficacy of the treatment was associated significantly with smoking status. Compared with never-smokers, ever-smokers had a better RR (40% vs 78%; P = .01), a longer PFS (2.5 months vs 6.4 months; P = .018), and had a trend toward an improved OS (9.0 months vs 11.2 months; P = .095). The effect of smoking on survival was apparent when ever-smokers were subdivided according to pack-years (PY) of smoking. Ever-smokers who had smoked >65 PY had a significantly longer OS compared with ever-smokers who had smoked ≤65 PY or never-smokers (20.6 months vs 10.6 months vs 9.0 months, respectively; log-rank P = 0.032). In multivariate analysis, PY >65 was predictive of longer survival (hazard ratio, 0.280; 95% confidence interval, 0.113-0.694).
  
  
  CONCLUSIONS
  The current results indicated that simvastatin in combination with irinotecan and cisplatin did not improve the survival of patients with ED-SCLC. Although the subgroup analysis by smoking status was exploratory, the addition of simvastatin to irinotecan and cisplatin may improve the outcome of heavy smokers with ED-SCLC.
authors.affiliation: Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea. jymama@ncc.re.kr
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Han
authors.forename: Kun Young
authors.initials: KY
authors.lastname: Lim
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Yu
authors.forename: Tak
authors.initials: T
authors.lastname: Yun
authors.forename: Heung Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy*; D012907:Smoking
chemical_list: D008055:Lipids; D008074:Lipoproteins; D000077146:Irinotecan; D019821:Simvastatin; D002945:Cisplatin; D002166:Camptothecin