title: A randomized, double-blind, placebo-controlled, phase II study of oral talactoferrin in combination with carboplatin and paclitaxel in previously untreated locally advanced or metastatic non-small cell lung cancer.
abstract: BACKGROUND
  The aim of the study is to investigate the activity and safety of oral talactoferrin (TLF) plus carboplatin and paclitaxel (C/P) in patients with previously untreated stage IIIB/IV non-small cell lung cancer.
  
  
  METHODS
  Patients (n = 110) were randomly assigned to receive C/P plus either TLF (C/P/T) or placebo (C/P/P). The primary objective of this exploratory study was assessment of confirmed response rate (RR) in the prospectively defined evaluable population with a one-tailed p = 0.05. Secondary objectives included assessment of progression-free survival (PFS), duration of response, overall survival (OS), and safety.
  
  
  RESULTS
  The trial met the primary end point of improvement in confirmed RR in the prospectively defined evaluable population. Compared with the C/P/P group, RR increased in the C/P/T group by 18% (29-47%; p = 0.05) and 15% (27-42%; p = 0.08) in the evaluable and intent-to-treat populations, respectively. Compared with the C/P/P group, the C/P/T group had a longer median PFS (4.2 versus 7.0 months), OS (8.5 versus 10.4 months), and duration of response (5.5 versus 7.6 months), although the differences were not statistically significant. Adverse events (AEs) were consistent with C/P therapy. There were fewer total AEs (472 versus 569; two-tailed p = 0.003) and grade 3/4 AEs (78 versus 105; p = 0.05) in the C/P/T group compared with the C/P/P group.
  
  
  CONCLUSIONS
  TLF, in combination with C/P, demonstrated an apparent improvement in RR, PFS, and OS in patients with previously untreated stage IIIB/IV non-small cell lung cancer and appears to enhance activity without significant additional toxicity. These results need to be confirmed in a phase III trial.
authors.affiliation: Department of Medical Oncology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, India.
authors.forename: Raghunadharao
authors.initials: R
authors.lastname: Digumarti
authors.forename: Yenyun
authors.initials: Y
authors.lastname: Wang
authors.forename: Ganapathi
authors.initials: G
authors.lastname: Raman
authors.forename: Dinesh C
authors.initials: DC
authors.lastname: Doval
authors.forename: Suresh H
authors.initials: SH
authors.lastname: Advani
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Julka
authors.forename: Purvish M
authors.initials: PM
authors.lastname: Parikh
authors.forename: Shekhar
authors.initials: S
authors.lastname: Patil
authors.forename: Shona
authors.initials: S
authors.lastname: Nag
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Madhavan
authors.forename: Ajay
authors.initials: A
authors.lastname: Bapna
authors.forename: Annantbhushan A
authors.initials: AA
authors.lastname: Ranade
authors.forename: Atul
authors.initials: A
authors.lastname: Varadhachary
authors.forename: Rajesh
authors.initials: R
authors.lastname: Malik
mesh_terms: D000284:Administration, Oral; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007781:Lactoferrin / Q000008:administration & dosage / Q000009:adverse effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C515276:talactoferrin alfa; D016190:Carboplatin; D007781:Lactoferrin; D017239:Paclitaxel