title: Preclinical characterization of CG53135 (FGF-20) in radiation and concomitant chemotherapy/radiation-induced oral mucositis.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the activity of CG53135 (FGF-20), a protein with in vitro mitogenic activity on epithelial and mesenchymal cells, in two in vivo models of oral mucositis (OM).
  
  
  METHODS
  Radiation or concomitant chemotherapy/radiation-induced OM was elicited in hamsters. Activity of CG53135 was assessed at different doses and regimens in the models. Bromodeoxyuridine (BrdUrd) incorporation and pharmacokinetic studies were also performed to correlate in vivo activity of CG53135 with exposure.
  
  
  RESULTS
  In the hamster radiation model, administration of CG53135 (600 or 1200 micro g/day, i.p.) on days 3-15 resulted in a statistically significant (P < 0.001) reduction in days spent with severe mucositis. CG53135 administered at 12 mg/kg, i.p. (days 1-2 or 1-8) in the concomitant chemotherapy/radiation model resulted in a statistically significant (P < 0.001) reduction in severe mucositis. Maximal BrdUrd incorporation was observed in cheek pouch and jejunal tissues at 8 h, and peak plasma levels of CG53135 were reached 1 h after administration.
  
  
  CONCLUSIONS
  CG53135 demonstrates potent, regimen-dependent activity in hamster models of OM. The activity was regimen dependent. BrdUrd incorporation studies confirmed that CG53135 had proliferative activity in vivo with a favorable pharmacokinetic profile. Based in part on work described herein, CG53135 has received approval from the United States Food and Drug Administration to be evaluated in a Phase I clinical trial of cancer patients at risk for developing OM.
authors.affiliation: CuraGen Corp, Branford, Connecticut 06405, USA. ealvarez@curagen.com
authors.forename: Enrique
authors.initials: E
authors.lastname: Alvarez
authors.forename: Edward G
authors.initials: EG
authors.lastname: Fey
authors.forename: Pascal
authors.initials: P
authors.lastname: Valax
authors.forename: Zachary
authors.initials: Z
authors.lastname: Yim
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Peterson
authors.forename: Medhi
authors.initials: M
authors.lastname: Mesri
authors.forename: Michael
authors.initials: M
authors.lastname: Jeffers
authors.forename: Matthew
authors.initials: M
authors.lastname: Dindinger
authors.forename: Nancy
authors.initials: N
authors.lastname: Twomlow
authors.forename: Ashwini
authors.initials: A
authors.lastname: Ghatpande
authors.forename: William J
authors.initials: WJ
authors.lastname: LaRochelle
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Sonis
authors.forename: Henri S
authors.initials: HS
authors.lastname: Lichenstein
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002610:Cheek / Q000473:pathology; D004396:Coloring Agents / Q000494:pharmacology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005346:Fibroblast Growth Factors / Q000627:therapeutic use*; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007583:Jejunum / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000473:pathology*; D009092:Mucous Membrane / Q000187:drug effects / Q000528:radiation effects; D011832:Radiation Injuries / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013280:Stomatitis / Q000139:chemically induced / Q000188:drug therapy; D013997:Time Factors
chemical_list: D004396:Coloring Agents; C416003:FGF20 protein, human; D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors; D001973:Bromodeoxyuridine; D005472:Fluorouracil