title: Randomized phase II trial of irinotecan with paclitaxel or gemcitabine for non-small cell lung cancer: association of UGT1A1*6 and UGT1A1*27 with severe neutropenia.
abstract: OBJECTIVE
  Irinotecan-containing regimens are known to be active and tolerable in patients with non-small cell lung cancer (NSCLC). A randomized phase II trial was conducted to evaluate the efficacy of irinotecan plus paclitaxel or gemcitabine for previously untreated stage IIIB or stage IV NSCLC.
  
  
  METHODS
  Previously untreated patients with adequate organ function who gave written informed consent were randomly assigned to receive irinotecan (50 mg/m on days 1, 8, and 15) plus paclitaxel (180 mg/m on day 1) every 4 weeks (IP group) or irinotecan (100 mg/m on days 1 and 8) plus gemcitabine (1000 mg/m on days 1 and 8) every 3 weeks (IG group). The primary endpoint was the response rate. We also evaluated the relationship of response and toxicity to polymorphisms of the uridine diphosphate glucuronosyltransferase (UGT) gene.
  
  
  RESULTS
  Eighty patients were enrolled, and 78 patients were eligible (38 in the IP group and 40 in the IG group). The response rate was 31.6% (95% confidence interval: 17.5-48.7%) in the IP group and 20.0% (9.1-35.6%) in the IG group. The median progression-free survival time was 86 days and 145 days, respectively. Both regimens were well tolerated. The most common severe adverse event was grade 4 neutropenia (36.8% and 10.0%, respectively), which was associated with UGT1A1*6 and UGT1A1*27. UGT polymorphisms did not correlate with response.
  
  
  CONCLUSIONS
  Irinotecan plus paclitaxel may be more active against NSCLC than irinotecan plus gemcitabine. The UGT1A1*6 and UGT1A1*27 genotypes might be useful predictors of grade 4 neutropenia in patients who receive irinotecan-based chemotherapy.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Soda
authors.forename: Mikio
authors.initials: M
authors.lastname: Oka
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Kinoshita
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Fukuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takatani
authors.forename: Seiji
authors.initials: S
authors.lastname: Nagashima
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Soejima
authors.forename: Takashi
authors.initials: T
authors.lastname: Kasai
authors.forename: Katsumi
authors.initials: K
authors.lastname: Nakatomi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Masuda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsukamoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology*; D017239:Paclitaxel / Q000008:administration & dosage; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine; D000099148:UGT1A1 Enzyme
chemical_list: D002166:Camptothecin; D003841:Deoxycytidine; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D017239:Paclitaxel; D000093542:Gemcitabine; D000099148:UGT1A1 Enzyme