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.
Sonis, S.T. (2009). Efficacy of palifermin (keratinocyte growth factor-1) in the amelioration of oral mucositis. Core Evidence, 4(1), 199-205.
To evaluate the evidence supporting the use of palifermin for its approved indication in patients undergoing hematopoietic stem cell transplantation (HSCT) for hematologic maligancies, and for other populations at risk of oral mucositis
A total of 100 papers and four abstracts were retrieved. Full papers were used. Studies with level 2 or higher clinical evidence, studies that were not randomized clinical trials (RCTs), case reports, and economic evidence also were used.
The evidence review supported palefermin use in the amelioration of oral mucositis. Palifermin was associated with a reduced need for opioid analgesics, reduced risk of febrile neutropenia, reduced need for total parenteral nutrition (TPN), improved patient‐reported function, and reduced hospital stay. In addition, palifermin was associated with a decrease in the costs of mucositis-associated complications in autologus HSCT recepients. It must be noted that the this was not a decrease in costs associated with mucositis‐associated complications, but a decrease in costs because of the lower incidence of adverse outcomes in patients treated with palifermin.
Palefermin is effective in the treatment of mucositis and the need to receive mucotoxic conditioning regimens in preparation for HSCT.
RCTs are needed to investigate the benefits of palifermin in patients who are not diagnosed with head and neck cancer, as the risk of significant mucositis is unpredictable in these patients. Also, concerns exist that palifermin has the potential to stimulate primary or secondary tumor growth.
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.
von Bultzingslowen, I., Brennan, M.T., Spijkervet, F.K., Logan, R., Stringer, A., Raber-Durlacher, J.E., & Keefe, D. (2006). Growth factors and cytokines in the prevention and treatment of oral and gastrointestinal mucositis. Supportive Care in Cancer, 14, 519–527.
A systematic review of the English medical literature was performed. Only clinical trials were included in the first search, January 1966–May 2002. In the June 2002–May 2005 review, clinical and preclinical trials were included.
In the 2002 review, 35 studies were identified. In the 2005 review, 14 preclinical and 9 clinical studies were identified. Studies reporting on cytokines or growth factors for the amelioration of chemotherapy- and radiation-induced mucositis throughout the entire alimentary canal were included.
Based on the review, guidelines recommend palifermin at a dose of 60 mg/kg per day for three days prior to conditioning for hematologic malignancies receiving high-dose chemotherapy and total body irradiation (TBI) with autologous stem cell transplantation (SCT). Preliminary results indicated effectiveness for repifermin. Trials are in process for velafermin.
Two randomized studies of granulocyte colony-stimulating factor (G-CSF) showed reduction in mucositis incidence. Two cohort studies demonstrated reduced severity of mucositis. One study did not show any positive results for mucositis. Another showed that use of growth factors was not a significant determinant of oral mucositis. Two studies failed to demonstrate improvement with G-CSF in the radiation setting. Studies demonstrate conflicting results. No recommendation can be made at this time.
One cohort study with granulocyte macrophage colony-stimulating factor (GM-CSF) showed reduction in severity and duration of oral mucositis. Another study showed no effect on radiation-induced oral mucositis. Two studies showed some positive effects for radiation-induced mucositis. Studies demonstrated conflicting results. No recommendation can be made at this time. Two studies with GM-CSF mouthwash demonstrated no positive effects. The Multinational Association of Supportive Care in Cancer guideline has been updated to suggest that GM-CSF mouthwash not be used for the prevention of mucositis in the transplant setting.
For other agents, evidence was insufficient or toxicities too severe to recommend use.
Blijlevens, N., de Chateau, M., Krivan, G., Rabitsch, W., Szomor, A., Pytlik, R., … Niederwieser, D. (2013). In a high-dose melphalan setting, palifermin compared with placebo had no effect on oral mucositis or related patient's burden. Bone Marrow Transplantation, 48, 966–971.
To evaluate efficacy of palifermin versus placebo for prevention of oral mucositis (OM), as well as burden of patients with multiple myeloma (MM) who receive autologous stem cell transplant (SCT)
This randomized study compared three groups: (1) placebo, (2) palifermin on days -6, -5, -4, 0, 1, and 2 (pre-/post-SCT), and (3) palifermin on days 0, 1, and 2 (post-SCT). The palifermin dose was 60 µg/kg per day IV. Patients were assessed daily for OM from day 2 until day 32 or discharge.
This was a multisite, inpatient study conducted in the Netherlands.
This was a randomized, placebo-controlled, parallel-group study.
Palifermin was unable to reduce OM or OM-related patient burden in patients with MM undergoing transplant.
Short term of use of palifermin for auto-SCT in patients with MM undergoing transplant was not effective in reducing OM. The fact that authors suggest that hyperkeratosis may have been incorrectly interpreted as OM suggests that correct assessment can be an issue in evaluating this symptom. Findings suggest that the specific timing of use of this agent may be critical. In using palifermin, nurses need to be aware of the appropriate timing in concert with timing of antineoplastic treatment and treatment effects.
Gholizadeh, N., Mehdipoor, M., Sajadi, H., & Moosavi, M.S. (2016). Palifermin and chlorhexidine mouthwashes in prevention of chemotherapy-induced mucositis in children with acute lymphocytic leukemia: A randomized controlled trial. Journal of Dentistry, 17, 343–347. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136413/pdf/JDS-17-343.pdf
To assess the effectiveness of palifermin in preventing mucositis in children with acute lymphocytic leukemia (ALL) undergoing chemotherapy
A clinical trial of 90 children with ALL who were randomized to receive chlorhexidine or palifermin. One group received 60 mcg/kg palifermin as an IV bolus once daily three days before and three days after chemotherapy. The other group received chlorhexidine mouthwash administered once daily three days before and three days after chemotherapy.
Randomized, controlled trial
The World Health Organization (WHO) Oral Toxicity Scale was used for grading mucositis. The data were analyzed with two-way ANOVA.
The group that used the palifermin had a decreased incidence and severity of chemotherapy-induced mucositis.
Palifermin reduced oral mucositis in children with ALL.
In this study, palifermin has reduced the severity of mucositis in children with ALL who received induction and intensification chemotherapy.
Langner, S., Staber, P.B., Schub, N., Gramatzki, M., Grothe, W., Behre, G., … Neumeister, P. (2008). Palifermin reduces incidence and severity of oral mucositis in allogeneic stem-cell transplant recipients. Bone Marrow Transplantation, 42, 275–279.
Palifermin was administered at 60 mcg/kg per day for three consecutive days before the initiation of conditioning therapy and again after graft infusion.
A group of 30 patients who had been treated with palifermin and undergone allogeneic hematopoietic stem-cell transplantation (HSCT) were retrospectively compared to a control group of 30 consecutive untreated patients receiving myeloablative conditioning.
The study was conducted from May 2005 to December 2006 in Austria and Germany.
The study was conducted within a compassionate use program.
The World Health Organization (WHO) Oral Toxicity Scale was used.
Lauritano, D., Petruzzi, M., Di Stasio, D., & Lucchese, A. (2014). Clinical effectiveness of palifermin in prevention and treatment of oral mucositis in children with acute lymphoblastic leukaemia: A case-control study. International Journal of Oral Science, 6, 27–30.
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 for pediatric patients with acute lymphoblastic leukemia
Twenty patients received palifermin and other 20 patients didn’t. The palifermin group received a 60 mg/kg IV bolus per day for three consecutive days before and three consecutive days after transplant (a total of six doses). All patients were evaluated for 30 days.
This study demonstrated a statistically significant reduction in the duration of parenteral nutrition (p = .002), duration of mucositis (p = .003), and the average grade of mucositis (p = .03). Other measures were not significant. The statistical analysis showed that the drug decreased the severity of mucositis.
These data suggest that palifermin could be a valid therapeutic adjuvant to improve quality of life for pediatric patients with leukemia.
Palifermin decreased the duration of oral mucositis in pediatric patients being treated for leukemia. Nurses should be aware that this intervention may compliment other interventions to reduce oral mucositis in this population.
Le, Q.T., Kim, H.E., Schneider, C.J., Murakozy, G., Skladowski, K., Reinisch, S., … Henke, M. (2011). Palifermin reduces severe mucositis in definitive chemoradiotherapy of locally advanced head and neck cancer: A randomized, placebo-controlled study. Journal of Clinical Oncology, 29, 2808–2814.
To evaluate the efficacy and safety of palifermin in the reduction of oral mucositis (OM) associated with definitive chemoradiotherapy for locally advanced head and neck cancer (HNC)
The study was conducted in a multi-institutional setting.
Patients were undergoing the active treatment phase of care.
This was a randomized, placebo-controlled study.
The incidence of severe OM was significantly lower in patients receiving palifermin than those receiving placebo (54% versus 69%). In the palifermin arm, the median time to severe OM was delayed, median duration of severe OM was shortened, and the incidence of xerostomia at grade 2 or more was lower, favoring palifermin; however, the differences were not significant after multiplicity adjustment.
Opioid analgesic use, average mouth and throat soreness scores, and chemoradiotherapy compliance were not significantly different between treatment arms.
Adverse events were similar between arms. The most common study drug related adverse events were rash, flushing, and dysgeusia. After median follow-up of 25.8 months, overall survival and progression-free survival were similar between the treatment arms.
There was no mention as to whether the study was blinded to the researchers.
Oral mucositis is a severe complication of treatment for head and neck cancer, and effective treatment strategies are still needed. Although palifermin reduced severe functional OM, its role in the management of locally advanced HNC during chemotherapy remains unclear. Effective treatment strategies to manage OM associated with high-dose chemoradiotherapy still are needed.
Lucchese, A., Matarese, G., Ghislanzoni, L.H., Gastaldi, G., Manuelli, M., & Gherlone, E. (2016). Efficacy and effects of palifermin for the treatment of oral mucositis in patients affected by acute lymphoblastic leukemia. Leukemia and Lymphoma, 57, 820–827.
To study the efficacy of palifermin for prophylaxis of OM in pediatric patients undergoing hematopoetic cell transplant (HCT)
Patients were randomly assigned to receive either IV palifermin 60 mcg/kg per day starting three days prior to transplant conditioning chemotherapy or placebo. All patients received basic oral hygiene and invasive nutrition as needed. All other aspects of care were essentially the same between groups. OM was assessed daily from 7 days prior to transplantation to 28 days after transplantation. Assessment was conducted by the same clinician.
Significantly fewer patients in the palifermin group developed grade 2 (p = 0.038) and grade 4 (p = 0.006) mucositis compared to the placebo group. Grade 4 was seen in 11% of patients in the palifermin group and 59% of patients in the control group. Fewer patients in the palifermin group had any grade mucositis, but not all differences in grades were statistically significant. The duration of grade 3 and 4 OM in patients in the palifermin group was three days compared to eight days in the control group (p < 0.001). The only adverse reactions reported were rashes and altered taste, lasting for 48–72 hours. The cumulative morphine daily dose per body weight was lower in the palifermin group (p = 0.04).
Palifermin was shown to effectively reduce the severity, prevalence, and duration of OM among pediatric patients undergoing HCT and was not associated with any significant adverse effects.
Palifermin was shown to be beneficial to pediatric patients undergoing HCT for primary prophylaxis for OM. OM is one of the most painful and debilitating effects of high-dose myeloablative chemotherapy. Nurses can advocate for the consideration of palifermin in these patients. Additional research in support of these findings is warranted, and research regarding the potential role of palifermin in other types of chemotherapy regimens associated with OM is needed.
Milone, G., Leotta, S., Cupri, A., Fauci, A. L., Spina, P., Parisi, M., . . . Tripepi, G. (2014). Palifermin reduces infection rate and hyperfibrinogenemia in patients treated with high-dose chemotherapy based on beam or BU-thiothepa. Bone Marrow Transplantation, 49, 1193–1197.
To assess the effect of palifermin on mucositis and infection risk according to conditioning regimen used, and to evaluate the effect of palifermin on fibrinogen levels
This is a retrospective study of patients who underwent high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-SCT) because of hematologic malignancies. The authors evaluated the differences between a cohort of patients who received prophylaxis with palifermin and a matched control group of patients who did not receive this agent, and assessed the effect of palifermin on infection risk according to the conditioning regimen used, comparing BEAM, BU-CY, THIO-CY, and HD-PAM conditioning regimens.
Total of 120 patients who underwent SCT from 2000–2009 who either received palifermin prophylaxis or did not receive palifermin (control group)
Weekly blood cultures, serum galactomannan assay, and skin and oral culture swabs were used in afebrile patients. Standard febrile workup was used including blood and urine cultures, chest radiography (CXR), and a CT of the thorax within 72 hours of the onset of fever. Any infection arising during the first 30 days was evaluated. Fever of unknown origin (FUO), pneumonia, febrile gram-positive bacteremia, and CVC-related infections were all evaluated. Mucositis was assessed for all patients using daily inspection and grading according to daily mucositis scoring using Eastern Cooperative Oncology Group (ECOG) Common Terminology Criteria for Adverse Events (CTCAE) criteria. Gastrointestinal (GI) toxicity was deemed as severe if there were five or more stools per day.
Palifermin reduced rates of severe mucositis when evaluation was conducted taking into account conditioning type. There was a significant reduction in the severe mucositis rate in the BEAM/BUS group, whereas there was no significant reduction in the HD-PAM group. Palifermin had no effect on GI toxicity. FUO was significantly reduced in palifermin treated group. A reduction in severe infections (p = 0.06) existed in the BEAM/BUS group. A highly significant reduction in gram-positive infections existed in the BEAM/BUS group but not in HD-PAM group. Rate of patients with fevers was decreased in the palifermin group, but not significantly. A reduction in serum fibrinogen peak levels during the aplastic phase was observed with palifermin in the BEAM/BUS group but not in HD-PAM group.
Palifermin reduced FUO and severe infections unrelated to gram-positive bacteria with a more evident effect after conditioning based on BEAM/BUS. Severe mucositis was also reduced in the BEAM/BUS group but not in the HD-PAM group. The reduction in fibrinogen level substantiates the beneficial effect and may suggest a reduction in risk of mortality.
Nurses should monitor fever, mucositis, and onset of infection; educate patients on infection prevention and use of medications; and advocate for use of palifermin in high-risk populations, including the elderly, those receiving BEAM/BUS therapy, or heavily pretreated patients.
Nasilowska-Adamska, B., Rzepecki, P., Manko, J., Czyz, A., Markiewicz, M., Federowicz, I., … Marianska, B. (2007). The influence of palifermin (Kepivance) on oral mucositis and acute graft versus host disease in patients with hematological diseases undergoing hematopoietic stem cell transplant. Bone Marrow Transplantation, 40, 983–988.
To assess the use of palifermin in the prevention of oral mucositis (OM) and acute graft-versus-host disease (GVHD) after hematopoietic stem cell transplant (HSCT)
IV palifermin was administered at 60 mcg/kg for three consecutive days before and after conditioning therapy. These patients were compared to a retrospective control group.
This was a multicenter study conducted in Poland.
This was a retrospective control trial.
Incidence of all grades of mucositis was lower in the palifermin group (p < 0.001). Incidence of grades 3–4 was 13% in the palifermin group and 43% in the control group (p < 0.001). Mean duration was significantly lower (p < 0.001). No statistically significant differences in the onset of OM, duration of TPN, opioid use, incidence of febrile neutropenia, or severe infection were observed. No statistical significance in acute GVHD measures were observed, although the authors suggested that a decrease in acute GVHD may occur. Additional studies are necessary.
Adverse events (e.g., rash, pruritis, erythema, generalized edema, taste alteration, mouth or tongue thickness and discoloration, proteinuria) were mild in 15 patients, moderate in 15 patients, and severe but not life-threatening in 4 patients. No events caused discontinuation of palifermin.
Nguyen, D.T., Shayani, S., Palmer, J., Dagis, A., Forman, S.J., Epstein, J., & Spielberger, R. (2015). Palifermin for prevention of oral mucositis in allogeneic hematopoietic stem cell transplantation: A single-institution retrospective evaluation. Supportive Care in Cancer, 23, 3141–3147.
To evaluate possible differences between the severity and duration of oral mucositis (OM) and other clinical end points previously found to be associated with OM in patients who received palifermin compared to those who did not
A retrospective chart review of 99 consecutive patients who received an allogeneic hematopoietic stem cell transplantation (AHSCT) with palifermin from December 2006 to December 2009 was conducted, and 30 patients who received AHSCT from January to December 2005 served as control group (this group was treated before palifermin became standard of practice). Palifermin was administered for three consecutive days with the third dose 24 hours before the initiation of fractionated total body irradiation and three additional doses after the completion of the conditioning regimen (days 0–2). All patients received a comprehensive oral care regimen, and oral assessments were conducted every three days by a certified respiratory therapist.
OM developed in 95% of patients in the palifermin group and all 30 patients in the control group. Severe OM developed in 34% of the palifermin group and 80% of the control group (p < 0.0001) with the median duration of OM 13 days with palifermin and 18 days with the control. The median duration of sever OM was not found to be different between groups. The median duration patient-controlled analgesia use was shorter in the palifermin group as was the use of opioids. No significant difference in the duration of total parenteral nutrition use was found.
Palifermin reduced the incidence of severe OM and the overall duration of OM in this study. This supported the use of palifermin.
This study supported palifermin use in this population. However, additional studies providing evidence on quality of life and patient-reported outcomes are needed.
Schmidt, E., Thoennissen, N.H., Rudat, A., Bieker, R., Schliemann, C., Mesters, R.M., … Berdel, W.E. (2008). Use of palifermin for the prevention of high-dose methotrexate-induced oral mucositis. Annals of Oncology, 19, 1644–1649.
IV palifermin 60 mcg/kg per day was given for three consecutive days before chemotherapy cycle A2 or B2 and then for three consecutive days after chemotherapy. All patients received granulocyte colony-stimulating factor (G-CSF). Prophylactic treatment consisted of a number of agents, including tetracaine, chamomile, oral hygiene, and amphotericin B suspensions. Authors used previous studies as historical controls.
This study used a retrospective series of 10 patients with B cell acute lymphocytic leukemia (ALL) or aggressive B cell lymphoma. Patients had World Health Organization (WHO) Oral Mucositis grades of 3 or 4 during cycle A1 or B1 of high-dose methotrexate (HDMTX).
Patients were selected retrospectively from September 2004 to March 2007.
Shea, T.C., Kewalramani, T., Mun, Y., Jayne, G., & Dreiling, L.K. (2007). Evaluation of single-dose palifermin to reduce oral mucositis in fractionated total-body irradiation and high-dose chemotherapy with autologous peripheral blood progenitor cell transplantation. Journal of Supportive Oncology, 5(4, Suppl. 2), 60–61.
To evaluate the safety and efficacy of single-dose palifermin in reducing oral mucositis incidence in patients with hematologic malignancies undergoing peripheral blood progenitor cell transplant receiving total-body irradiation and high-dose chemotherapy
Patients were randomized to receive 60 mcg/kg palifermin once daily for three days before the start of fractionated total-body irradiation (TBI) (Arm A), 180 mcg/kg once only on day -1 (Arm B), day -2 (Arm C), or day -3 (Arm D) before starting fractionated TBI and stratified by etoposide use and number of days of TBI. All patients received 60 mcg/kg for three days post-transplantation.
The study reported on 47 patients receiving high-dose chemotherapy with an age range of 18–74 years. Patients had multiple cancer diagnoses.
The World Health Organization (WHO) Oral Toxicity Scale was used.
Spielberger, R., Stiff, P., Bensinger, W., Gentile, T., Weisdorf, D., Kewalramani, T., … Emmanouilides, C. (2004). Palifermin for oral mucositis after intensive therapy for hematologic cancers. New England Journal of Medicine, 351(25), 2590–2598.
IV palifermin (recombinant human keratinocyte growth factor) 60 mg/kg was given for three consecutive days immediately before a conditioning regimen (total body irradiation [TBI] plus high-dose [HD] chemo). Additional doses administered on days 0, 1, and 2.
The study was conducted in a multisite setting.
This was a placebo-controlled, double-blind, phase 3, randomized trial.
Patients in the palifermin group experienced statistically significant decreases in incidence and duration of mucositis.
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
Palifermin in autologous stem cell transplantation
Palfiermin in graft-versus-host disease
Other interventions for management of mucositis
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.
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.