title: Cisplatin combined with irinotecan or etoposide for untreated extensive-stage small cell lung cancer: A multicenter randomized controlled clinical trial.
abstract: BACKGROUND
  This study evaluated the efficacy and safety of irinotecan/cisplatin (IP) and etoposide/cisplatin (EP) in extensive-stage small cell lung cancer (ES-SCLC) and the distribution of uridine diphosphate glucuronosyltransferase (UGT1A1). The relationship between UGT1A1 genotypes and patient outcomes was also assessed.
  
  
  METHODS
  Patients with untreated ES-SCLC were randomly assigned to receive either IP or EP, and blood specimens were collected to test the genotypes of UGT1A1*28 and UGT1A1*6. The association of efficacy and toxicity of an IP regimen with UGT1A1 genotype was analyzed.
  
  
  RESULTS
  Of the 62 patients enrolled from three institutions, 30 patients were in the IP and 32 patients were in the EP arms, respectively. Disease control rates with IP and EP were 83.3% and 71.9%, respectively (P = 0.043). Median progression-free survival for IP and EP were both six months. Median overall survival for IP and EP were 18.1 and 15.8 months respectively, without significant difference. Grade 3-4 thrombocytopenia was more common with EP (18.8% vs. 6.7%; P = 0.035), while the incidence of diarrhea was higher with IP (70% vs. 15.6%; P = 0.008). The incidence of grade 1-4 late-onset diarrhea of wild-type, heterozygous, and homozygous UGT1A1*28 were 65.0%, 85.7%, and 66.7%, respectively (P = 0.037). UGT1A1*28 polymorphisms, Eastern Cooperative Oncology Group performance status, and chemotherapy cycles were essential factors affecting grade 1-4 late-onset diarrhea in logistic regression analysis.
  
  
  CONCLUSIONS
  The efficacy of the IP regimen was similar to the EP regimen for untreated ES-SCLC. UGT1A1 polymorphisms were associated with late-onset diarrhea; however, there was no influence on efficacy.
authors.affiliation: Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China.
authors.forename: Yuankai
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Oncology, Chinese, General Hospital, Medical School of Chinese Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China.
authors.forename: Xingsheng
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Medical Oncology, China-Japan Friendship Hospital Beijing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Han
keywords: Cisplatin; UGT1A1; etoposide; extensive-stage small cell lung cancer; irinotecan