title: A randomized trial of prophylactic palifermin on gastrointestinal toxicity after intensive induction therapy for acute myeloid leukaemia.
abstract: Gastrointestinal toxicity, including oral mucositis, is a frequent complication of intensive combination chemotherapy for acute myeloid leukaemia (AML) and contributes substantially to treatment-related mortality. We conducted a placebo-controlled randomized trial to evaluate the efficacy of palifermin (keratinocyte growth factor), given at 60 μg/kg per daily IV for 3 d before and after chemotherapy, for mucosal protection in adult patients with previously untreated AML receiving induction therapy with idarubicin, high-dose cytarabine and etoposide. Among 155 randomized patients, there was no statistically significant difference in the rate of grade 3 and 4 oral mucositis (primary study endpoint) between the two treatment arms (three in palifermin arm (4%), 8 in placebo arm (10%; P = 0·21); however, when considering the severity of oral mucositis (World Health Organization grade 0-4), there was evidence of reduced rates of higher grades of oral mucositis in the palifermin arm (P = 0·0007, test for trend). There was a statistically significantly lower rate of grades 3 and 4 gastrointestinal adverse events in the palifermin arm (21% vs. 44% in placebo arm; P = 0·003), mainly due to a reduction in severe diarrhoea (8% palifermin, 26% placebo; P = 0·01). Palifermin has activity as a mucosal protectant in AML patients receiving intensive chemotherapy. This trial is registered at ACTRN012605000095662.
authors.affiliation: Department of Haematology, Westmead Hospital, Sydney, NSW, Australia.
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bradstock
authors.forename: Emma
authors.initials: E
authors.lastname: Link
authors.forename: Marnie
authors.initials: M
authors.lastname: Collins
authors.forename: Juliana
authors.initials: J
authors.lastname: Di Iulio
authors.forename: Ian D
authors.initials: ID
authors.lastname: Lewis
authors.forename: Anthony
authors.initials: A
authors.lastname: Schwarer
authors.forename: Arno
authors.initials: A
authors.lastname: Enno
authors.forename: Paula
authors.initials: P
authors.lastname: Marlton
authors.forename: Uwe
authors.initials: U
authors.lastname: Hahn
authors.forename: Jeff
authors.initials: J
authors.lastname: Szer
authors.forename: Gavin
authors.initials: G
authors.lastname: Cull
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D051523:Fibroblast Growth Factor 7 / Q000008:administration & dosage*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013280:Stomatitis / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*
chemical_list: D003561:Cytarabine; D051523:Fibroblast Growth Factor 7; D005047:Etoposide; D015255:Idarubicin
keywords: acute myeloid leukaemia; chemotherapy; keratinocyte growth factor; mucositis; palifermin