title: Phase I trial of oral talactoferrin alfa in refractory solid tumors.
abstract: BACKGROUND
  Lactoferrin is an iron-binding glycoprotein first identified in breast milk as a protein product of mammary epithelial cells. Its immunomodulatory functions include activation of NK and lymphokine-activated killer cells and enhancement of PMN and macrophage cytotoxicity. Studies in animal models have shown promising anti-cancer activity. The purpose of the present study was to evaluate the safety and tolerability of talactoferrin alfa (talactoferrin; TLF) in humans, as well as pharmacokinetics and pharmacodynamics.
  
  
  METHODS
  Ten adult patients with progressive advanced solid tumors who had failed conventional chemotherapy were administered oral TLF at doses from 1.5 to 9 g/day, using a 2 weeks on, 2 weeks off schedule. Patients were evaluated for drug toxicity, tumor growth rate, talactoferrin pharmacokinetics and cytokine markers.
  
  
  RESULTS
  Talactoferrin was very well tolerated. No hematological, hepatic, or renal toxicities were reported. A single patient had Grade 2 diarrhea, and there were no Grade 3 or 4 toxicities. Following oral administration, significant levels of talactoferrin were undetectable in circulation, but a statistically significant increase in circulating IL-18, a pharmacodynamic indicator of talactoferrin activity, was observed. Of the eight patients who were radiologically evaluable, five (63%) had stable disease by RECIST criteria two months after start of therapy, including one patient with a minor response. Seven patients (88%) had a decrease in their tumor growth rate. The three patients with non-small cell lung cancer (NSCLC) all survived for at least one year following the start of talactoferrin monotherapy.
  
  
  CONCLUSIONS
  Talactoferrin is a promising, well-tolerated new agent that should be evaluated further in patients with refractory metastatic cancer.
authors.affiliation: Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, Texas, USA. thayes@bcm.tmc.edu
authors.forename: Teresa G
authors.initials: TG
authors.lastname: Hayes
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Falchook
authors.forename: Gauri R
authors.initials: GR
authors.lastname: Varadhachary
authors.forename: Dori P
authors.initials: DP
authors.lastname: Smith
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Davis
authors.forename: Hari M
authors.initials: HM
authors.lastname: Dhingra
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Hayes
authors.forename: Atul
authors.initials: A
authors.lastname: Varadhachary
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D020382:Interleukin-18 / Q000097:blood; D007781:Lactoferrin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D020382:Interleukin-18; D011994:Recombinant Proteins; C515276:talactoferrin alfa; D007781:Lactoferrin