A randomized trial of prophylactic palifermin on gastrointestinal toxicity after intensive induction therapy for acute myeloid leukaemia

Abstract

SummaryGastrointestinal 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 lg/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 = 0Á21); 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 = 0Á0007, 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 = 0Á003), mainly due to a reduction in severe diarrhoea (8% palifermin, 26% placebo; P = 0Á01). Palifermin has activity as a mucosal protectant in AML patients receiving intensive chemotherapy. This trial is registered at ACTRN012605000095662.

Prevention and Treatment of Chemotherapy and Radiotherapy Induced Oral Mucositis

“…In general, 18 studies chose the OM degree to estimate the final treatment outcomes [2,10,11,12,13,14,15,17,18,19,20,21,22,23,24,25,27,28]. 2 studies chose the manifestation of progression or remission of this disease [13,22], 7 studies—the duration of the disease [3,15,19,20,21,24,26] and 3 attempted to determine the time of occurrence of OM after the oncologic treatment had started [23,26,27]. One study evaluated the results according to questionnaires in which patients described their oral mucosa condition subjectively [16].…”

“…Bradstock et al [13] studied the effect of Palifermin (keratinocyte growth factor (KGF)), given 60 μg/kg daily IV for 3 days before and after chemotherapy, for mucosal protection. 155 subjects, who received combined chemotherapy, were included in the study (76 to palifermin and 79 to placebo groups).…”

“…A total of 20 out to 21 studies indicated localization of an oncological disease: hematologic cancer [2], colon cancer [3], head and neck cancer [10,11], hematologic cancer [12,13,14], head and neck cancer [15,16,17,18,19,20], hematologic cancer [21], breast cancer [22], head and neck cancer [23,24,25,26,27], hematological cancer [28]. In all studies, the oncologic treatment method is described: chemotherapy [2], combined chemotherapy and radiotherapy [3,10,11], radiotherapy [11], chemotherapy [12,13,14], combined chemotherapy and radiotherapy [15,16], radiotherapy [17,18], combined chemotherapy and radiotherapy [18], chemotherapy [19], combined chemotherapy and radiotherapy [20], radiotherapy [20], chemotherapy [21], combined chemotherapy and radiotherapy [22,23], radiotherapy [24], combined chemotherapy and radiotherapy [25], radiotherapy [26], combined chemotherapy and radiotherapy [27], chemotherapy [28].…”

“…In all studies, the oncologic treatment method is described: chemotherapy [2], combined chemotherapy and radiotherapy [3,10,11], radiotherapy [11], chemotherapy [12,13,14], combined chemotherapy and radiotherapy [15,16], radiotherapy [17,18], combined chemotherapy and radiotherapy [18], chemotherapy [19], combined chemotherapy and radiotherapy [20], radiotherapy [20], chemotherapy [21], combined chemotherapy and radiotherapy [22,23], radiotherapy [24], combined chemotherapy and radiotherapy [25], radiotherapy [26], combined chemotherapy and radiotherapy [27], chemotherapy [28]. …”

Wound repair and regeneration: Mechanisms, signaling, and translation

“…Furthermore, keratinocyte growth factor-1 (KGF-1; also known as FGF-7), which targets epidermal cells, has been reported to promote healing of skin wounds in mice (65). KGF-1 received FDA approval in 2004 and was marketed as palifermin or Kepivance for the prevention of severe oral mucositis in patients with hematological malignancies receiving high-dose chemotherapy (66). …”