title: Randomized phase III trial comparing bexarotene (L1069-49)/cisplatin/vinorelbine with cisplatin/vinorelbine in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: SPIRIT I.
abstract: OBJECTIVE
  This study evaluated whether the combination of the synthetic rexinoid bexarotene with first-line cisplatin/vinorelbine therapy provides additional survival benefit in patients with advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with stage IIIB with pleural effusion or stage IV NSCLC and Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to open-label bexarotene 400 mg/m(2)/d with cisplatin/vinorelbine or to cisplatin/vinorelbine alone. Antilipid agents were initiated on or before day 1 in the bexarotene arm. Primary efficacy end point was overall survival. Primary, secondary and supportive efficacy analyses were conducted.
  
  
  RESULTS
  A total of 623 patients (312 control, 311 bexarotene) were enrolled. Overall, no significant difference in survival occurred between the two treatment groups. However, an unplanned retrospective analysis showed that a subpopulation of bexarotene patients (n = 98 of 306) who experienced National Cancer Institute grade 3/4 hypertriglyceridemia had longer median survival compared with control patients (12.3 v 9.9 months; log-rank P = .08). Within that subgroup, those who benefited the most included males, smokers, those with stage IV disease, and those with a 6-month prior weight loss of 5% or more. Incidence, type and severity of grade 3/4 adverse events were comparable between arms, except for leukopenia (higher in chemotherapy arm) and hyperlipemia, hypothyroidism, dyspnea, and headache (higher in chemotherapy/bexarotene arm).
  
  
  CONCLUSIONS
  The addition of bexarotene to first-line chemotherapy did not increase survival in patients with advanced NSCLC. However, a subgroup (32%) of bexarotene-treated patients developing high-grade hypertriglyceridemia appeared to have better survival (12.3 months) than controls; thus triglyceride response may be a biomarker of survival benefit with bexarotene.
authors.affiliation: Lung Disease Centre, Oncology Department, ul.Szamarzewskiego, Poznań, Poland. rramlau@wcchpig.pl
authors.forename: Rodryg
authors.initials: R
authors.lastname: Ramlau
authors.forename: Petr
authors.initials: P
authors.lastname: Zatloukal
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.forename: Paul
authors.initials: P
authors.lastname: Schwarzenberger
authors.forename: Sergei V
authors.initials: SV
authors.lastname: Orlov
authors.forename: Maya
authors.initials: M
authors.lastname: Gottfried
authors.forename: Jose Rodrigues
authors.initials: JR
authors.lastname: Pereira
authors.forename: Guillermo
authors.initials: G
authors.lastname: Temperley
authors.forename: Rosa
authors.initials: R
authors.lastname: Negro-Vilar
authors.forename: Samia
authors.initials: S
authors.lastname: Rahal
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Zhang
authors.forename: Andres
authors.initials: A
authors.lastname: Negro-Vilar
authors.forename: Zofia E
authors.initials: ZE
authors.lastname: Dziewanowska
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077610:Bexarotene; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000139:chemically induced / Q000401:mortality; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D015996:Survival Rate; D013764:Tetrahydronaphthalenes / Q000009:adverse effects; D014280:Triglycerides / Q000097:blood*; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D014408:Biomarkers, Tumor; D013764:Tetrahydronaphthalenes; D014280:Triglycerides; D014747:Vinblastine; D000077610:Bexarotene; D002945:Cisplatin; D000077235:Vinorelbine