Niscola, P., Scaramucci, L., Giovannini, M., Ales, M., Bondanini, F., Cupelli, L., et al. (2009). Palifermin in the management of mucositis in hematological malignancies: Current evidences and future perspectives. Cardiovascular & Hematological Agents in Medicinal Chemistry, 7, 305–312. 

To review the role of palifermin and other current and potential treatments for chemotherapy-induced mucositis in the context of pathobiology in hematologic malignancies

Database searched was MEDLINE. Abstracts and published proceedings reporting the role of palifermin in the management of mucositis were reviewed. 

Search keywords were MeSH headings for chemotherapy, cyclophosphamide, etoposide, GI mucositis, GVHD, hematology, hematological malignancies, hematopoeietic stem cell transplantation, hemorrhagic  cystitis, HSCT, keratinocyte growth factor, KGF, leukemia, lymphoma, melphalan, methotrexate, mucositis, multiple myeloma, oncohematology, oral mucositis, pain, palifermin, radiation, radiotherapy, soreness, and total parenteral nutrition.

Palifermin in standard and high dose chemotherapy

• Only case reports and one small study were included.  It was concluded that insufficient evidence exists to support palifermin use in patients without transplantation.

Palifermin in autologous stem cell transplantation

• One study in 212 patients showed that among those who developed grade 3 or 4 mucositis, the duration was shorter in those who received palifermin (p < 0.001).
• No randomized controlled trials and only a few additional small studies and case series were included.
• Insufficient evidence was found to make any recommendation regarding palifermin in these cases.

Palfiermin in graft-versus-host disease

• Two studies using palifermin were cited, but no appraisal of findings was provided. It was noted that palifermin is used in this setting, and the biological rationale and brief findings in animal models are stated.

Other interventions for management of mucositis

• Findings from meta analyses indicate that, while some interventions have some benefit, the strength of the evidence was variable, and findings in one meta-analysis reported that no single intervention was capable of completely preventing oral mucositis.
• A number of cytokines and growth factors other than palifermin were indicated that have been or are currently being investigated to treat or prevent mucositis. The mechanism of potential activity and effects seen were provided.
• Other agents outlined included chlorhexidine, povidone iodine, pilocarpine, histamine gel, benzydamine oral rinse, amifostine, systemic glutamine, nonsteroidal anti-inflammatory drugs, and oral doxepin. Evidence was deemed insufficient to determine the efficacy and role of these agents.

Control of oral mucositis pain and provision of supportive therapy and regular assessment are critical management components.

This article provided information about various approaches in the management and prevention of oral mucositis in patients with hematologic malignancies and outlined the biologic mechanism of action and observed effects from review of the literature. However, it provided little information about the actual strength of evidence and is based on a limited literature search. No clear description of rationale for article inclusion was included.

The authors concluded that evidence supports the use of palifermin, but the article stated elsewhere that evidence in this area is insufficient in some patient groups, and only one nonrandomized study is cited where the duration of high-grade mucositis was shorter in patients who received palifermin, suggesting a biased view of the role of palifermin.

This article can provide useful information regarding the mechanism of action of various treatments, but it is not helpful in determining relative effectiveness of various interventions.