title: Randomized Phase II study of two opposite administration sequences of irinotecan and cisplatin in patients with advanced nonsmall cell lung carcinoma.
abstract: BACKGROUND
  Combined chemotherapy with irinotecan and cisplatin (IP) is active in patients with nonsmall cell lung carcinoma (NSCLC). However, the optimal administration schedule needs to be defined to maximize its synergic effect. The authors evaluated the efficacy, toxicity, and pharmacokinetics (PK) of IP chemotherapy given on two administration sequences in chemotherapy-naive patients with NSCLC.
  
  
  METHODS
  Eighty eligible patients were assigned randomly to receive 1 of 2 irinotecan and cisplatin administration sequences on Day 1: irinotecan followed by cisplatin (I-P) (n = 39 patients) or cisplatin followed by irinotecan (P-I) (n = 41 patients). Treatment was comprised of irinotecan at a dose of 80 mg/m(2) intravenously on Days 1 and 8 and cisplatin at a dose of 60 mg/m(2) intravenously on Day 1 of a 21-day cycle for a maximum of 6 cycles. For PK analysis, serial plasma samples were obtained on Day 1 of the first cycle.
  
  
  RESULTS
  In total, 77 patients were assessable for efficacy. The overall response rate was 47%, and there was a trend in favor of P-I (54%) compared with I-P (39%). In multivariate logistic regression analysis, the P-I sequence and female gender were found to be significant predictors of a better response (P = 0.047 and P = 0.011, respectively). Overall toxicity profiles and PK parameters were similar in both arms.
  
  
  CONCLUSIONS
  IP chemotherapy showed promising activity with a favorable 1-year survival rate. For future clinical use, the authors recommend administering cisplatin first and then irinotecan, because that sequence was associated with a higher response rate.
authors.affiliation: Research Institute and Hospital, Center for Lung Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Han
authors.forename: Hyeong-Seok
authors.initials: HS
authors.lastname: Lim
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: So Young
authors.initials: SY
authors.lastname: Ju
authors.forename: Sung Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Hyae Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Park
authors.forename: Chun Gun
authors.initials: CG
authors.lastname: Park
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin