title: Randomized phase I trial of recombinant human keratinocyte growth factor plus chemotherapy: potential role as mucosal protectant.
abstract: OBJECTIVE
  To evaluate the safety of recombinant human keratinocyte growth factor (KGF) when administered with fluorouracil (FU) in patients with metastatic colorectal cancer.
  
  
  METHODS
  Patients (N = 81) received KGF by intravenous (IV) bolus on days 1 to 3, followed by FU 425 mg/m2/d IV bolus plus leucovorin 20 mg/m2/d IV on days 4 to 8. KGF dose levels were 1, 10, 20, 40, 60, and 80 microg/kg/d. A randomized, placebo-controlled design was employed (2:1 randomization of KGF to placebo). Oral mucositis was assessed by examination on days 1, 4, 8, 15, and 28. In addition, patients provided daily assessments of oral symptoms using a self-administered questionnaire.
  
  
  RESULTS
  Skin and oral events occurred in 13 of 18 patients (eight patients, grade 1; four patients, grade 2; and one patient, grade 3) treated with 60 and 80 microg/kg of KGF and three of 11 patients treated with 40 microg/kg (grade 1). These symptoms were dose limiting in three cases (ie, in two of 10 patients treated with 80 microg/kg and in one of eight patients treated with 60 microg/kg). The frequency of grade 2 to 4 mucositis was 43% in patients treated with KGF, compared with 67% in patients treated with placebo (P =.06). Patient self-assessments of oral pain and clinical assessments of mucositis showed good correlation (Kendall's tau = 0.75).
  
  
  CONCLUSIONS
  KGF is generally well tolerated when administered IV at doses up to 40 microg/kg/d for 3 days before a 5-day course of FU plus leucovorin. A clinically meaningful biologic effect was also suggested in that patients treated with the epithelial growth factor KGF had a lower rate of grade 2 to 4 mucositis than did patients treated with placebo.
authors.affiliation: Fox Chase Cancer Center, 7701 Burholme Ave, Philadelphia, PA 19111, USA. nj_meropol@fccc.edu
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Meropol
authors.forename: Robert A
authors.initials: RA
authors.lastname: Somer
authors.forename: John
authors.initials: J
authors.lastname: Gutheil
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Pelley
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Modiano
authors.forename: Eric K
authors.initials: EK
authors.lastname: Rowinsky
authors.forename: Mace L
authors.initials: ML
authors.lastname: Rothenberg
authors.forename: Spencer W
authors.initials: SW
authors.lastname: Redding
authors.forename: Cuneyt M
authors.initials: CM
authors.lastname: Serdar
authors.forename: Bin
authors.initials: B
authors.lastname: Yao
authors.forename: Robert
authors.initials: R
authors.lastname: Heard
authors.forename: Lee S
authors.initials: LS
authors.lastname: Rosen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000681:Amylases / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D005260:Female; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005472:Fluorouracil / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000009:adverse effects; D008049:Lipase / Q000097:blood; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000187:drug effects*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C496453:FGF7 protein, human; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D008049:Lipase; D000681:Amylases; D002955:Leucovorin; D005472:Fluorouracil