Annals of Oncology Advance Access originally published online on October 9, 2006
Annals of Oncology 2007 18(5):817-826; doi:10.1093/annonc/mdl332
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© 2006 European Society for Medical Oncology
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Palifermin (recombinant keratinocyte growth factor-1): a pleiotropic growth factor with multiple biological activities in preventing chemotherapy- and radiotherapy-induced mucositis
1 Department of Haematology, University Medical Centre, St Radboud, Nijmegen, The Netherlands
2 Division of Oral Medicine, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA
* Correspondence to: Dr N. Blijlevens, Department of Haematology, University Medical Centre, St Radboud, PO Box 9101 6500 HB Nijmegen, The Netherlands. Tel: +31 24 361 4762; Fax: +31 24 354 2080; E-mail: N.Blijlevens{at}HEMAT.umcn.nl
Oral and intestinal mucositis are among the most significant dose-limiting toxic effects of intensive cancer treatment and are associated with adverse clinical and economic outcomes. Palifermin (KepivanceTM), an N-truncated recombinant human keratinocyte growth factor-1, is the first agent to be approved for prevention of oral mucositis. Keratinocyte growth factor, a potent epithelial mitogen, appears to play a major role in the healing process. Palifermin has multiple biological activities that appear to protect the mucosal epithelium and promote its early regeneration after irradiation- and chemotherapy-induced injury. These include inhibition of epithelial cell apoptosis and DNA damage, up-regulation of detoxifying enzymes and down-regulation of pro-inflammatory cytokines, as well as enhanced migration, proliferation and differentiation of epithelial cells. Palifermin reduces the incidence, severity and duration of oral mucositis in patients with haematological malignancies undergoing myelotoxic conditioning therapy and haematopoietic stem-cell transplantation. Clinical sequelae, including febrile neutropenia and resource use (opioid analgesia and parenteral feeding), are concomitantly reduced. Other potential applications being explored include use in the solid tumour setting, reduction of intestinal mucositis and reduction of GVHD in allogenic transplantation. Thus, the development of palifermin and other potential new agents for preventing chemotherapy- and radiotherapy-induced mucositis represents an important breakthrough in oncological supportive care.
Key words: anti-neoplastic agents, adverse effects, growth factors, haematopoietic stem-cell transplantation, keratinocyte growth factor, mucositis, palifermin
Received for publication February 1, 2006. Revision received July 17, 2006. Accepted for publication August 14, 2006.
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