title: Single-dose palifermin prevents severe oral mucositis during multicycle chemotherapy in patients with cancer: a randomized trial.
abstract: BACKGROUND
  Mucositis can be a serious complication of cancer treatment. Palifermin reduces mucositis when given in multiple doses to patients undergoing hematopoietic stem-cell transplantation.
  
  
  OBJECTIVE
  To evaluate the efficacy of palifermin given as a single dose before each cycle in patients receiving multicycle chemotherapy.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00267046)
  
  
  METHODS
  The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
  
  
  METHODS
  48 patients with sarcoma were randomly assigned in a 2:1 ratio to receive palifermin or placebo. All patients received doxorubicin-based chemotherapy (90 mg per m(2) of body surface area over 3 days, by infusion).
  
  
  METHODS
  Palifermin (180 µg per kg of body weight) or placebo was administered intravenously as a single dose 3 days before each chemotherapy cycle (maximum, 6 cycles). Patients who had severe mucositis received open-label palifermin in subsequent cycles.
  
  
  METHODS
  Oral assessment of mucositis by using World Health Organization (WHO) oral toxicity scale (grades 0 to 4), with moderate to severe mucositis (grades 2 to 4) as the main outcomes; patient-reported outcome questionnaire; and daily symptom record diary.
  
  
  RESULTS
  A median of 6 blinded cycles (range, 1 to 6) were completed by the palifermin group and 2 (range, 1 to 6) by the placebo group. Compared with placebo, palifermin reduced the cumulative incidence of moderate to severe (grade 2 or higher) mucositis (44% vs. 88%; P < 0.001; difference, -44 percentage points [95% CI, -71 to -16 percentage points) and severe (grade 3 or 4) mucositis (13% vs. 51%; P = 0.002; difference, -38 percentage points [CI, -67 to -9 percentage points]). The main adverse effects were thickening of oral mucosa (72% in the palifermin group vs. 31% in the placebo group; P = 0.007) and altered taste. Seven of the 8 patients who had severe mucositis in the placebo group received open-label palifermin. None of these patients had severe mucositis in the subsequent cycles (a total of 17) with open-label palifermin.
  
  
  CONCLUSIONS
  Study limitations include smaller sample size for the control group, inclusion of only patients with sarcoma, and perceived unblinding of the treatment because of notable differences between the biologic effects of palifermin and placebo.
  
  
  CONCLUSIONS
  A single dose of palifermin before each cycle reduced the incidence and severity of mucositis. The drug was generally well tolerated, but most patients experienced thickening of oral mucosa. Further investigation is needed to determine whether palifermin use will facilitate greater adherence to chemotherapy regimens by reducing mucositis.
authors.affiliation: University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. svadhanr@mdanderson.org
authors.forename: Saroj
authors.initials: S
authors.lastname: Vadhan-Raj
authors.forename: Jonathan
authors.initials: J
authors.lastname: Trent
authors.forename: Shreyaskumar
authors.initials: S
authors.lastname: Patel
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhou
authors.forename: Marcella M
authors.initials: MM
authors.lastname: Johnson
authors.forename: Dejka
authors.initials: D
authors.lastname: Araujo
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Ludwig
authors.forename: Shana
authors.initials: S
authors.lastname: O'Roark
authors.forename: Ann M
authors.initials: AM
authors.lastname: Gillenwater
authors.forename: Carlos
authors.initials: C
authors.lastname: Bueso-Ramos
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: Robert S
authors.initials: RS
authors.lastname: Benjamin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D004311:Double-Blind Method; D004317:Doxorubicin / Q000009:adverse effects; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology; D012509:Sarcoma / Q000188:drug therapy*; D013280:Stomatitis / Q000188:drug therapy / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D051523:Fibroblast Growth Factor 7; D004317:Doxorubicin