Palifermin is a type of recombinant human cell growth factor that stimulates epithelial cell proliferation and differentiation. It also has direct cytoprotective effects. Palifermin has been studied in patients with cancer for the prevention and management of mucositis.
Stokman, M.A., Spijkervet, F.K., Boezen, H.M., Schouten, J.P., Roodenburg, J.L., & deVries, E. G. (2006). Preventive intervention possibilities in radiotherapy and chemotherapy-induced oral mucositis: Results of meta-analysis. Journal of Dental Research, 85, 690–700.
Databases searched were MEDLINE, EMBASE, and CINAHL (1966–2004).
Search keywords were [neoplasms] AND [(mucositis OR stomatitis)] AND [limit to (clinical trial OR randomized-controlled trials)].
Studies were included in the review if they were
The search yielded 109 publications. Of these, five were not aimed at prevention, 13 were nonrandomized, and 29 did not contain data in a comprehensive form. Seventeen articles stood alone in terms of intervention, and 45 articles included meta-analyses. Studies with zero or infinite odds ratios were omitted because variances could not be calculated with accuracy. Sample sizes ranged from 14–502.
Patients with various cancer diagnoses receiving chemotherapy, radiation therapy, or combination chemoradiotherapy.
Of the 27 interventions identified for the prevention of oral mucositis, meta-analysis could be performed on eight. Four interventions showed a preventive effect on the development or severity of oral mucositis: PTA (polymyxin E, tobramycine, and amphotericin B) lozenges or paste, systemic administration of granulocyte macrophage–colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF), oral cooling, and amifostine.
Of 14 studies (each on a different intervention type), nine showed some positive results; however, methodological flaws (e.g., small sample sizes, lack of double-blind or placebo-controlled designs) prevented those studies from demonstrating effectiveness. One study of benzydamine (Epstein et al., 2001) showed an improved ulcer-free rate and decreased incidence of ulcer and erythema.
Palifermin demonstrated positive results for the prevention of mucositis in patients with hematologic malignancies undergoing autologous stem cell transplantation.
Rosen, L.S., Abdi, E., Davis, I.D., Gutheil, J., Schnell, F.M., Zalcberg, J., … Clarke, S. (2006). Palifermin reduces the incidence of oral mucositis in patients with metastatic colorectal cancer treated with fluorouracil-based chemotherapy. Journal of Clinical Oncology, 24(433), 5194–5200.
Palifermin was administered at 40 mcg/kg IV for three consecutive days before each of two chemotherapy cycles with fluorouracil (5-FU) or leucovorin (LV).
The study reported on patients with metastatic colorectal cancer receiving 5-FU or LV. The group receiving palifermin had 28 patients, and the group receiving placebo had 36 patients.
This was a phase I and II randomized double-blind, placebo-controlled study.
Vadhan-Raj, S., Trent, J., Patel, S., Zhou, X., Johnson, M.M., Araujo, D., … Benjamin, R.S. (2010). Single-dose palifermin prevents severe oral mucositis during multicycle chemotherapy in patients with cancer: a randomized trial. Annals of Internal Medicine, 153, 358–367.
To evaluate the efficacy and safety of palifermin given as a single dose before each cycle in patients receiving doxorubicin-based multicycle chemotherapy
Patients were randomly assigned in a 2:1 ratio to receive palifermin or placebo.
This study was conducted at a single-site at the University of Texas M.D. Anderson Cancer Center.
Patients were undergoing the active treatment phase of care.
This was a randomized, double-blind, placebo-controlled trial.
Palifermin significantly reduced the incidence of moderate to severe (grade 2 or higher) mucositis (44% versus 88%; p <0.001) and severe mucositis (13% versus 51%; p < 0.002).
A single dose of palifermin before each cycle reduced the incidence and severity of mucositis. It also demonstrated effectiveness as secondary prophylaxis in a few patients with severe mucositis.
Mucositis and the pain it causes can significantly impact patients with cancer during treatment. Further research is needed to establish the alleviation of pain and the improved ability to drink, eat, and talk. If the mucosal lining is maintained, it would be important to establish if there are fewer infections, use of total parenteral nutrition (TPN) to maintain nutrition, and use of opiod patient-controlled analgesia (PCA) for pain control.
Vitale, K.M., Violago, L., Cofnas, P., Bishop, J., Jin, Z., Bhatia, M., ... Satwani, P. (2014). Impact of palifermin on incidence of oral mucositis and healthcare utilization in children undergoing autologous hematopoietic stem cell transplantation for malignant diseases. Pediatric Transplantation, 18, 211–216.
To determine if administration of palifermin during autologous hematopoietic stem cell transplantation (AHSCT) in children will lower incidence of oral mucositis and shorter duration of hospitalization
Patients received palifermin 60 µg/kg/day IV for the three consecutive days prior to myeloablative conditioning and for the three consecutive days after the end of chemotherapy. All patients received six total doses. Treating physicians were responsible for the decision to administer palifermin. Data were collected using electronic and paper medical charts.
No statistical difference in grades III-IV mucositis (p = 1.0), lower incidence in grades III–IV (p = 0.047) in patients receiving solid tumor regimen, and no difference in length of hospitalization
Palifermin administration did not result in a statistically significant decrease in incidence and grade of oral mucositis, nor did it result in shorter hospitalization.
High doses of chemotherapy prior to AHSCT causes significant morbidity due to oral mucositis. A larger study is needed to confirm findings of lower incidence of grades III and IV mucositis in the solid tumor regimens.
Peterson, D.E., Bensadoun, R.J., Roila, F., & ESMO Guidelines Working Group. (2010). Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines. Annals of Oncology, 21(Suppl. 5), v261–v265.
To summarize the evidence around the use of radiotherapy, standard-dose chemotherapy, and high-dose chemotherapy with or without total body irradiation plus hematopoietic stem cell transplantation (HSCT) for the management of mucositis
The primary author was the principal investigator on the National Institutes of Health (NIH) R13 Conference Grant that provided partial support for the symposium “Oral Complications of Emerging Cancer Therapies,” 14-15 April 2009, Bethesda, MD, USA. Production of a Journal of the National Cancer Institute (JNCI) Monograph for conference publications was supported by an unrestricted educational grant form Biovirum, which owned palifermin at the time of the publication. Peterson also is a member of the Scientific Advisory Board and a paid consultant for the GI Co., Inc, which is responsible for the development of recombinant intestinal trefoil factor, for which the phase II study is cited in the references.
The mucositis guidelines reported contain few changes from the previous two versions of the ESMO Clinical Practice Guidelines. With the 2009 MASCC/ISCO Mucositis Study Group in June 2009, it was decided that no new guidelines were warranted based on the current published literature. Progress has been made in the understanding of molecular basis of mucositis. Evidence-based, cancer-specific identification of risk factors and management of mucositis depend on clinical research so that approval of new drugs and devices will be possible.
Raber-Durlacher, J.E., von Bultzingslowen, I., Logan, R.M., Bowen, J., Al-Azri, A.R., Everaus, H., … Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). (2013). Systematic review of cytokines and growth factors for the management of oral mucositis in cancer patients. Supportive Care in Cancer, 21(1), 343–355.
To review the literature and define clinical practice guidelines for use of cytokines and growth factor agents for the prevention or treatment of oral mucositis from chemotherapy or radiation therapy in patients with various types of cancer receiving radiation, chemotherapy, or hemapoietic stem cell transplant (HSCT)
In this evidence-based guideline, two independent reviewers scored level of evidence by Somerfield and Hadorn criteria. Following panel consensus, findings were integrated into guidelines.
Databases searched were Ovid, MEDLINE, and hand searching.
Search keywords included all types of cytokines and growth factors.
Inclusion and exclusion criteria were not specified.
Patients were undergoing the active antitumor treatment phase of care.
Out of 1,718 papers that were initially retrieved, 64 studies were included in the systematic review.
Palifermin 60 mcg/kg/day for three days prior to conditioning and three days post-transplantation was recommended in patients receiving HSCT. No guideline was possible for palifermin use in other patient types. For granulocyte colony-stimulating factor (G-CSF), no guideline was possible. No guidelines were possible for granulocyte macrophage colony-stimulating factor (GM-CSF) mouthwash, topical transforming growth factor beta, mil-derived growth factor, epidermal growth factor, interleukin-II, ALT 104, or recombinant human intestinal trefoil factor.
Very limited research has been done in children. Guidelines do not specify if recommendations are for adults and children. Most studies had relatively low levels of evidence. Sample sizes were not reported.
Use of palifermin for mucositis prevention in HSCT recipients was recommended.