Randomized, double-blind, placebo-controlled study of palifermin for the prevention of mucositis in patients receiving doxorubicin-based chemotherapy

Abstract

9547 Background: Mucositis is a common complication in patients (pts) receiving chemotherapy (CT). Palifermin, a recombinant keratinocyte growth factor, has been shown to reduce mucositis when given as 3 doses both before and after intensive therapy with hematopoietic stem cell support. The purpose of this study was to evaluate the safety and efficacy of palifermin administered as a single dose prior to CT in pts receiving multi-cycle CT. Methods: 48 sarcoma pts were randomized 2:1 to palifermin vs placebo. All pts received doxorubicin (90mg/m2 by continuous infusion over 3 days) with ifosfamide (10 gm/m2over 4 days) or cisplatin (120 mg/m2 on day1). The blinded study drug (palifermin 180 mcg/kg or placebo) was administered IV 3 days prior to CT. The cycles were repeated at 3 weeks (max 6 cycles). Pts who experienced ≥ gr 3 mucositis received open label palifermin in subsequent cycles. Results: All 48 pts have been enrolled; 12 are still on treatment. There were 25 males and 23 females, with median age 41 (range, 15–64 yrs). So far, 7 pts have experienced severe (≥ gr 3 WHO criteria) mucositis, and received open label palifermin in subsequent cycles. None of the 7 pts experienced severe mucositis in the open label phase. The common side effects included feeling of thickness of tongue and oral mucosa, and altered taste. No serious adverse event related to the study drug was observed. Histopathologic evaluation of buccal mucosal biopsies in a few pts performed, revealed increased epithelial thickness and elevated proliferative index using Ki-67 marker after the study drug. The study is planned to be completed and un-blinded by May 2008. Conclusions: Palifermin alleviated severe mucositis in pts who previously experienced severe mucositis during multi-cycle CT. Parameters Blinded study drug cycle* Open-label Palifermin cycle* P value Wilcoxon signed-rank No. of pts with ≥ gr 3 mucositis 7 0 <0.001 Median cycle No. 2 3 Days of ≥ gr 3 6 (3–9) 0 (0–0) 0.016 Days of ≥ gr 2 9 (5–13) 0 (0–4) 0.016 Weight change (kg) −3.3 (−1.3–−8.9) +0.5 (−4.1–+1.7) 0.031 * Same dose CT Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen