Phase I study of the tolerability and pharmacokinetics of palifermin in children undergoing allogeneic hematopoietic stem cell transplantation.

Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation (Impact Factor: 3.15). 04/2012; 18(8):1309-14. DOI: 10.1016/j.bbmt.2012.04.013
Source: PubMed

ABSTRACT The maximum tolerated dose of palifermin, a keratinocyte growth factor, in children is not known, and its pharmacokinetics in this population has not been well studied. This is a phase I study of palifermin was designed to evaluate its tolerability at doses of 40, 60, and 90 μg/kg/day in children age 2-18 years of age, receiving a myeloablative preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT). In each cohort, palifermin was given for 3 consecutive days before the preparative regimen and for 3 days after the stem cell infusion. Twelve patients were enrolled. Palifermin 90 μg/kg/day was tolerated in 6 patients without dose-limiting toxicity. All patients had at least 1 adverse event, mostly National Cancer Institute grade 1 or 2 severity. Skin rash, grade 2 or lower, was the most common adverse event, seen in 67% of patients. Only 3 patients (25%) had mucositis. The area under the concentration-time curve increased proportionally to the dose, and approximately 97% of palifermin exposure occurred in the first 24 hours after administration. Palifermin clearance increased linearly with body weight, supporting dosing by body weight. The mean clearance was 1893 mL/hour/kg, and it did not change significantly between administration of the first and last doses (P = .80). The mean elimination half-life was 4.6 hours. Our data show that palifermin was tolerated at a dose of 90 μg/kg/day, and exhibits linear pharmacokinetics in children undergoing allogeneic HSCT.

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    ABSTRACT: Palifermin has been demonstrated to decrease the incidence of severe oral mucositis in adults following TBI containing conditioning regimens prior to AHSCT. The impact of palifermin on the incidence of oral mucositis in children undergoing AHSCT has never been studied. We compared the effect of palifermin on the incidence of oral mucositis and supportive care in 58 children undergoing myeloablative AHSCT; 25 children received palifermin and 33 children did not receive palifermin (control arm). Oral mucositis was graded as per WHO criteria. The demographic characteristics were comparable between the two arms. Results comparing the palifermin vs. control arm showed that the incidence of grade III-IV oral mucositis was 20% vs. 42.4% (p = 0.072). The number of days patients received patient-controlled analgesia and total parenteral nutrition in the palifermin vs. control arm were 8.80 ± 8.39 vs. 8.30 ± 8.54 (p = 0.826) and 13.52 ± 11.32 vs. 11.55 ± 9.63 (p = 0.484), respectively. The average length of hospitalization in the palifermin vs. control arm was 31.44 ± 7.42 vs. 28.61 ± 10.38 (p = 0.252), respectively. In this study, we were unable to demonstrate a statistical difference in the incidence of oral mucositis and other supportive care needs or a decrease in hospital stay between the two arms.
    Pediatric Transplantation 03/2014; 18(2):211-6. DOI:10.1111/petr.12192 · 1.63 Impact Factor
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    ABSTRACT: Mucositis is one of the most significant toxicities in cancer patients undergoing cytotoxic treatment. It can have a negative impact on both quality of life and health economics. Severe oral mucositis can contribute to hospitalization, need for narcotic analgesics, total parentral nutrition, suboptimal delivery of anti-neoplastic treatment, and morbidity and mortality. Palifermin, a recombinant derivative of human keratinocyte growth factor, is the first active agent approved by the FDA for the prevention of severe oral mucositis in patients undergoing haematopoietic stem cell transplantation (HSCT). Several studies have also shown significant reduction in the incidence, severity and/or duration of oral mucositis in other high-risk settings such as concurrent chemoradiotherapy (CT/RT) for patients with head and neck cancer, and use of mucotoxic chemotherapeutic agents such as doxorubicin in sarcoma and fluorouracil for the treatment of colorectal cancer. The reduction in mucositis has translated into amelioration of symptoms and improvement in daily functioning as measured by patient-reported outcome in multiple studies. The clinical response to palifermin appears to be related in part to epithelial proliferation and mucosal thickening. Palifermin also has other potential clinical applications including the acceleration of immune reconstitution and inhibition of graft-versus-host disease in patients undergoing HSCT, and mitigation of dysphagia in lung cancer patients treated with concurrent CT/RT. Palifermin is generally well tolerated with mild-to-moderate skin and oral adverse events. Future studies may expand the use of palifermin into other areas that would benefit from its cytoprotective and regenerative effects.
    Journal of Cellular and Molecular Medicine 11/2013; DOI:10.1111/jcmm.12169 · 3.70 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the efficacy of palifermin, an N-terminal truncated version of endogenous keratinocyte growth factor, in the control of oral mucositis during antiblastic therapy. Twenty patients undergoing allogeneic stem-cell transplantation for acute lymphoblastic leukaemia were treated with palifermin, and compared to a control group with the same number of subjects and similar inclusion criteria. Statistical analysis were performed to compare the outcomes in the treatment vs. control groups. In the treatment group, we found a statistically significant reduction in the duration of parenteral nutrition (P=0.002), duration of mucositis (P=0.003) and the average grade of mucositis (P=0.03). The statistical analysis showed that the drug was able to decrease the severity of mucositis. These data, although preliminary, suggest that palifermin could be a valid therapeutic adjuvant to improve the quality of life of patients suffering from leukaemia.International Journal of Oral Science (2013) 5, doi:10.1038/ijos.2013.93; published online 20 December 2013.
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