title: Long-Term Safety Outcomes in Patients with Hematological Malignancies Undergoing Autologous Hematopoietic Stem Cell Transplantation Treated with Palifermin to Prevent Oral Mucositis.
abstract: The purpose of our study was to compare long-term safety outcomes (overall survival, disease progression, and incidence of secondary malignancies) between palifermin and placebo in the prevention of oral mucositis in patients with hematological malignancies undergoing autologous hematopoietic stem cell transplantation (HSCT). Patients were enrolled between 1997 and 2005 into 4 phase I to III studies (3 double-blind placebo-controlled and 1 open-label) conducted at 31 sites in Australia, Europe, and the United States. Survival outcomes (overall survival, progression-free survival) were compared using hazard ratios (HRs) estimated with a Cox model that included treatment group, baseline age, disease type, Eastern Cooperative Oncology Group performance status, country, and presence of prior radiotherapy as covariates. The incidence of secondary malignancies was compared with a chi-square test. A total of 672 patients were randomized into the studies (428 palifermin and 244 placebo). The median follow-up time for subjects alive at last visit was 7.9 years (range, .1 to 14.9) for palifermin and 8.8 years (range, .1 to 14.8) for placebo. Palifermin-treated patients had overall survival (HR, 1.01; 95% confidence interval [CI], .78 to 1.31; P = .921) and progression-free survival times (HR, 1.04; 95% CI, .83 to 1.31; P = .733) that were comparable with placebo-treated patients. Secondary malignancies were reported by 13% of palifermin-treated patients versus 11% of placebo patients (P = .477). Breakdown into secondary hematological malignancies (7% versus 6%) or solid tumors (6% versus 6%) did not suggest any differences between the treatment groups. After a follow-up of up to 15 years, comparable long-term safety outcomes (overall survival, progression-free survival, and incidence of secondary malignancies) were observed for palifermin- and placebo-treated patients undergoing autologous HSCT.
authors: Cardinal Bernardin Cancer Center, Division of Hematology and Oncology, Department of Medicine, Loyola University Medical Center, Maywood, Illinois. Electronic address: pstiff@lumc.edu.
authors: Patrick J
authors: PJ
authors: Stiff
authors: Sobi, SE-112 76, Stockholm, Sweden; 4Pharma AB, Stockholm, Sweden.
authors: Mika
authors: M
authors: Leinonen
authors: Sobi, SE-112 76, Stockholm, Sweden.
authors: Torbjörn
authors: T
authors: Kullenberg
authors: Sobi, SE-112 76, Stockholm, Sweden.
authors: Mattias
authors: M
authors: Rudebeck
authors: Sobi, SE-112 76, Stockholm, Sweden.
authors: Maarten
authors: M
authors: de Chateau
authors: City of Hope Department of Hematology and Hematopoietic Cell Transplantation, Los Angeles, California; Southern California Permanente Medical Group, Los Angeles, California.
authors: Ricardo
authors: R
authors: Spielberger
mesh_terms: D000328:Adult; D064592:Autografts; D018572:Disease-Free Survival; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000008:administration & dosage*; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D013280:Stomatitis / Q000209:etiology / Q000517:prevention & control*; D015996:Survival Rate
chemical_list: D051523:Fibroblast Growth Factor 7
keywords: Hematopoietic stem cell transplantation; Mucositis; Palifermin; Second malignancies