Single-Dose Palifermin Prevents Severe Oral Mucositis During Multicycle Chemotherapy in Patients With Cancer A Randomized Trial

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. Design: Randomized, double-blind, placebo-controlled trial. (Clinical Trials.gov registration number: NCT00267046) Setting: The University of Texas M. D. Anderson Cancer Center, Houston, Texas. Patients: 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). Intervention: Palifermin (180 mu g 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. Measurements: 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. Limitations: 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. Conclusion: 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.