title: Phase I/II study of vinorelbine and exisulind as first-line treatment of advanced non-small cell lung cancer in patients at least 70 years old: a wisconsin oncology network study.
abstract: BACKGROUND
  Exisulind is an apoptotic agent with preclinical activity in non-small cell lung cancer (NSCLC). Vinorelbine is safe and effective in older patients with advanced NSCLC. We assessed these agents together as palliative treatment for older patients with advanced NSCLC.
  
  
  METHODS
  Chemotherapy-naive patients >/=70-years-old with stage IIIB-IV NSCLC and a performance status (PS) </=2 were eligible. Primary endpoints were the maximum tolerated dose (phase I) and time-to-progression (phase II) of oral exisulind with 25 mg/m/wk of intravenous vinorelbine on a 28-day cycle. Patients with clinical benefit after 6 cycles of this combination received exisulind alone.
  
  
  RESULTS
  Fourteen phase I patients (median PS 1; median age 78 years) were enrolled. Dose-limiting toxicities included grade 3 constipation (one patient), grade 3 febrile neutropenia (one patient) and grade 3 diarrhea (one patient). The maximum tolerated dose of oral exisulind with 25 mg/m/wk of intravenous vinorelbine was 125 mg twice daily. Thirty phase II patients (median PS 1; median age 78 years) were enrolled. Grade >/=3 neutropenia occurred in 14/30 patients. Two patients experienced neutropenic fever. There were no complete responses, one partial response and 12 patients with stable disease as their best response. The objective response rate was 4.0% (95% CI: 0.1-20.4%). Phase II median time-to-progression was 4.7 months (95% CI: 3.1-9.3 months) and median OS was 9.6 months (95% CI: 6.6-19.1 months).
  
  
  CONCLUSIONS
  This combination is safe, seems to have activity in the elderly with advanced NSCLC and a PS </=2, and warrants further investigation.
authors.affiliation: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, Wisconsin, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Attia
authors.forename: Anne M
authors.initials: AM
authors.lastname: Traynor
authors.forename: Kyungmann
authors.initials: K
authors.lastname: Kim
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Merchant
authors.forename: Tien
authors.initials: T
authors.lastname: Hoang
authors.forename: Harish G
authors.initials: HG
authors.lastname: Ahuja
authors.forename: Peter A
authors.initials: PA
authors.lastname: Beatty
authors.forename: Richard M
authors.initials: RM
authors.lastname: Hansen
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Masters
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Oettel
authors.forename: Gary R
authors.initials: GR
authors.lastname: Shapiro
authors.forename: Martha M
authors.initials: MM
authors.lastname: Larson
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Larson
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller