title: Randomized, double-blind, placebo-controlled phase II study of single-agent oral talactoferrin in patients with locally advanced or metastatic non-small-cell lung cancer that progressed after chemotherapy.
abstract: OBJECTIVE
  To investigate the activity and safety of oral talactoferrin (TLF) in patients with stages IIIB to IV non-small-cell lung cancer (NSCLC) for whom one or two prior lines of systemic anticancer therapy had failed.
  
  
  METHODS
  Patients (n = 100) were randomly assigned to receive either oral TLF (1.5 g in 15 mL phosphate-based buffer) or placebo (15 mL phosphate-based buffer) twice per day in addition to supportive care. Oral TLF or placebo was administered for a maximum of three 14-week cycles with dosing for 12 consecutive weeks followed by 2 weeks off. The primary objective was overall survival (OS) in the intent-to-treat (ITT) patient population. Secondary objectives included progression-free survival (PFS), disease control rate (DCR), and safety.
  
  
  RESULTS
  TLF was associated with improvement in OS in the ITT patient population, meeting the protocol-specified level of significance of a one-tailed P = .05. Compared with the placebo group, median OS increased by 65% in the TLF group (3.7 to 6.1 months; hazard ratio, 0.68; 90% CI, 0.47 to 0.98; P = .04 with one-tailed log-rank test). Supportive trends were also observed for PFS and DCR. TLF was well tolerated and, generally, there were fewer adverse events (AEs) and grade ≥ 3 AEs reported in the TLF arm. AEs were consistent with those expected in late-stage NSCLC.
  
  
  CONCLUSIONS
  TLF demonstrated an apparent improvement in OS in patients with stages IIIB to IV NSCLC for whom one or two prior lines of systemic anticancer therapy had failed and was well tolerated. These results should be confirmed in a global phase III trial.
authors.affiliation: Tata Memorial Hospital, Mumbai, India.
authors.forename: Purvish M
authors.initials: PM
authors.lastname: Parikh
authors.forename: Ashok
authors.initials: A
authors.lastname: Vaid
authors.forename: Suresh H
authors.initials: SH
authors.lastname: Advani
authors.forename: Raghunadharao
authors.initials: R
authors.lastname: Digumarti
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Madhavan
authors.forename: Shona
authors.initials: S
authors.lastname: Nag
authors.forename: Ajay
authors.initials: A
authors.lastname: Bapna
authors.forename: Jagdev S
authors.initials: JS
authors.lastname: Sekhon
authors.forename: Shekhar
authors.initials: S
authors.lastname: Patil
authors.forename: Preeti M
authors.initials: PM
authors.lastname: Ismail
authors.forename: Yenyun
authors.initials: Y
authors.lastname: Wang
authors.forename: Atul
authors.initials: A
authors.lastname: Varadhachary
authors.forename: Junming
authors.initials: J
authors.lastname: Zhu
authors.forename: Rajesh
authors.initials: R
authors.lastname: Malik
mesh_terms: D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007781:Lactoferrin / Q000008:administration & dosage / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D017671:Platinum Compounds / Q000008:administration & dosage; D016016:Proportional Hazards Models; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D017671:Platinum Compounds; C515276:talactoferrin alfa; D007781:Lactoferrin