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Critical Reviews in Oncology/hematology Apr 2022Palifermin, a recombinant keratinocyte growth factor promotes thickening of the mucosa, minimising severity of mucositis caused by chemotherapy and radiotherapy. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Palifermin, a recombinant keratinocyte growth factor promotes thickening of the mucosa, minimising severity of mucositis caused by chemotherapy and radiotherapy.
OBJECTIVE
To synthesise published literature on palifermin for the management of oral mucositis, in patients receiving chemotherapy and/or radiotherapy, aiming to ascertain recommendations for practice.
METHODS
Databases searched were Medline, Embase, IPA and CIANHL. A meta-analysis included randomised controlled trials (RCT) for palifermin compared to placebo or no palifermin, with the key data extracted being number of events of severe mucositis (defined by WHO criteria grade 3 or 4).
RESULTS
The meta-analysis included 10 RCT. Patients were treated for solid and haematological malignancy. Analysis suggested benefit of palifermin decreasing the incidence of severe mucositis in solid tumours RR0.76 [95%CI 0.63-0.92;p = 0.004], haematological malignancy RR0.63 [95 %CI 0.48-0.82;p = 0.0007] and overall RR0.69 [95 %CI 0.59-0.81;p < 0.0001].
CONCLUSION
Palifermin reduces the incidence of severe mucositis up to 30 % in patients receiving treatment with chemotherapy and/or radiotherapy.
Topics: Fibroblast Growth Factor 7; Hematologic Neoplasms; Humans; Mucositis; Neoplasms; Stomatitis
PubMed: 35101586
DOI: 10.1016/j.critrevonc.2022.103606 -
The Annals of Pharmacotherapy Jan 2007To assess the efficacy, toxicity, and potential cost benefit of palifermin in the prevention of chemotherapy- and radiation-induced mucositis. (Review)
Review
OBJECTIVE
To assess the efficacy, toxicity, and potential cost benefit of palifermin in the prevention of chemotherapy- and radiation-induced mucositis.
DATA SOURCES
MEDLINE and PubMed database searches were conducted (1966-May 2006) using the following search terms: palifermin, human keratinocyte growth factor, fibroblast growth factor, mucositis, and stomatitis.
STUDY SELECTION AND DATA EXTRACTION
All published clinical trials and abstracts examining the use of palifermin, as well as information from the manufacturer, were included.
DATA SYNTHESIS
Severe mucositis resulting from anticancer therapies increases healthcare expenditures and negatively impacts patients' quality-of-life. Radiation therapy to the head and neck, as well as stem cell transplant conditioning regimens, have the highest incidence of severe mucositis. Consequences include prolonged hospitalization, need for parenteral nutrition, increased risk of infection, and severe pain. Palifermin is a recombinant human keratinacyte growth factor indicated in patients with hematologic malignancies who are undergoing stem cell transplant. In a randomized, placebo-controlled, Phase III trial, palifermin significantly reduced the incidence and duration of severe mucositis and days of parenteral nutrition and opioid analgesics in patients undergoing autologous stem cell transplant. The most common adverse effects of palifermin were rash, pruritus, cough, and taste alterations. Data in patients with solid tumors are limited, and there is a theoretical risk of stimulating tumor growth.
CONCLUSIONS
Treatment with palifermin appears to decrease the severity and duration of severe mucositis following autologous stem cell transplant. Use in these patients appears justified; however, use in non-stem cell transplant patients should be discouraged until more efficacy and toxicity data are available.
Topics: Animals; Antineoplastic Agents; Fibroblast Growth Factor 7; Humans; Mouth Mucosa; Mucositis; Radiotherapy
PubMed: 17190850
DOI: 10.1345/aph.1G473 -
Drugs in R&D 2004Amgen is developing a recombinant human form of keratinocyte growth factor (rHu-KGF) called palifermin [AMJ 9701]. Keratinocyte growth factor (KGF, fibroblast growth... (Review)
Review
Amgen is developing a recombinant human form of keratinocyte growth factor (rHu-KGF) called palifermin [AMJ 9701]. Keratinocyte growth factor (KGF, fibroblast growth factor 7, FGF-7) is a form of an endogenous epithelial tissue growth factor that stimulates the growth of cells on the surface of the gastrointestinal tract. Palifermin is being developed for oral mucositis (stomatitis), for which it is undergoing review by the US FDA.At BioSquare-2004, Biovitrum stated that it has entered into an agreement with Amgen, under which Biovitrium has co-promotion rights to palifermin in Nordic countries, including Scandinavia and Iceland. Amgen also plans to investigate the efficacy and safety of palifermin in patients with oral mucositis associated with other forms of chemotherapy. Amgen has stated that palifermin is also undergoing phase II trials in patients with solid tumours.
Topics: Animals; Antineoplastic Agents; Clinical Trials, Phase I as Topic; Clinical Trials, Phase III as Topic; Fibroblast Growth Factor 7; Fibroblast Growth Factors; Graft Rejection; Humans; Mice; Mouth Diseases; Neoplasms; Randomized Controlled Trials as Topic
PubMed: 15563240
DOI: 10.2165/00126839-200405060-00008 -
Journal of Cellular and Molecular... Sep 2013Keratinocyte growth factor (KGF) is a paracrine-acting epithelial mitogen produced by cells of mesenchymal origin, that plays an important role in protecting and... (Review)
Review
Keratinocyte growth factor (KGF) is a paracrine-acting epithelial mitogen produced by cells of mesenchymal origin, that plays an important role in protecting and repairing epithelial tissues. Pre-clinical data initially demonstrated that a recombinant truncated KGF (palifermin) could reduce gastrointestinal injury and mortality resulting from a variety of toxic exposures. Furthermore, the use of palifermin in patients with hematological malignancies reduced the incidence and duration of severe oral mucositis experienced after intensive chemoradiotherapy. Based upon these findings, as well as the observation that KGF receptors are expressed in many, if not all, epithelial tissues, pre-clinical studies have been conducted to determine the efficacy of palifermin in protecting different epithelial tissues from toxic injury in an attempt to model various clinical situations in which it might prove to be of benefit in limiting tissue damage. In this article, we review these studies to provide the pre-clinical background for clinical trials that are described in the accompanying article and the rationale for additional clinical applications of palifermin.
Topics: Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Epithelium; Fibroblast Growth Factor 7; Humans; Protective Agents; Regeneration
PubMed: 24151975
DOI: 10.1111/jcmm.12091 -
Cutis Aug 2023
Topics: Humans; Fibroblast Growth Factor 7; Antineoplastic Agents; Cisplatin; Neck; Exanthema; Stomatitis
PubMed: 37820333
DOI: 10.12788/cutis.0835 -
Drugs 2005Palifermin, a recombinant human keratinocyte growth factor (KGF), mimics the actions of endogenous KGF and has shown efficacy in the management of myelotoxic... (Review)
Review
Palifermin, a recombinant human keratinocyte growth factor (KGF), mimics the actions of endogenous KGF and has shown efficacy in the management of myelotoxic therapy-induced oral mucositis in cancer patients. In a randomised, double-blind trial in patients with haemtaological malignancies receiving conditioning radiochemotherapy before undergoing autologous stem cell transplant, intravenous palifermin 60 microg/kg/day (two 3-day cycles, administered before myelotoxic therapy and after transplant) significantly reduced the median duration (primary endpoint) [3 vs 9 days] and incidence (63% vs 98%) of WHO grade 3 or 4 oral mucositis, compared with placebo. Patient-reported outcomes also showed significant improvement with palifermin treatment, which was associated with significant reductions in healthcare resource utilisation, compared with placebo. The drug was generally well tolerated, with skin/oral toxicities, pain/arthralgias and dysaesthesia being the most common palifermin-related adverse reactions.
Topics: Animals; Clinical Trials as Topic; Double-Blind Method; Fibroblast Growth Factor 7; Hematopoietic Stem Cell Transplantation; Humans; Keratinocytes; Randomized Controlled Trials as Topic; Stomatitis; Transplantation Conditioning; Treatment Outcome
PubMed: 16225371
DOI: 10.2165/00003495-200565150-00008 -
International Journal of Biological... Nov 2021Palifermin (Kepivanceā¢) is the first therapeutic approved by the Food and Drug Administration for preventing and managing the oral mucositis provoked by myelotoxic and... (Review)
Review
Palifermin (Kepivanceā¢) is the first therapeutic approved by the Food and Drug Administration for preventing and managing the oral mucositis provoked by myelotoxic and mucotoxic therapies. Palifermin is a recombinant protein generated from human keratinocyte growth factor (KGF) and imitates the function of endogenous KGF. KGF is an epithelial mitogen involved in various biological processes which belongs to the FGF family. KGF possesses a high level of receptor specificity and plays an important role in tissue repair and maintaining of the mucosal barrier integrity. Based on these unique features, palifermin was developed to enhance the growth of damaged epithelial tissues. Administration of palifermin has shown success in the reduction of toxicities of chemotherapy and radiotherapy, and improvement of the patient's quality of life. Notwithstanding all merits, the clinical application of palifermin is limited owing to its instability and production challenges. Hence, a growing number of ongoing researches are designed to deal with these problems and enhance the physicochemical and pharmaceutical properties of palifermin. In the current review, we discuss KGF structure and function, potential therapeutic applications of palifermin, as well as the latest progress in the production of recombinant human KGF and its challenges ahead.
Topics: Antineoplastic Agents; Apoptosis; Carrier Proteins; Cell Movement; Fibroblast Growth Factor 7; Heparin; Humans; Models, Molecular; Protein Conformation; Quality of Life; Receptor, Fibroblast Growth Factor, Type 2; Stomatitis; Wound Healing
PubMed: 34606789
DOI: 10.1016/j.ijbiomac.2021.09.151 -
European Journal of Oncology Nursing :... 2007Oral mucositis (OM) is an extremely debilitating side effect of certain high-dose chemotherapy and radiotherapy regimens. It is especially prevalent in patients with... (Review)
Review
Oral mucositis (OM) is an extremely debilitating side effect of certain high-dose chemotherapy and radiotherapy regimens. It is especially prevalent in patients with haematological malignancies who undergo myeloablative therapy and autologous haematopoietic stem cell transplantation (HSCT). Severe erosion of the lining of the oral cavity can make patients' everyday activities, including eating, drinking, swallowing, and talking, difficult or even impossible. Palifermin (Kepivance) was approved in Europe in 2005 for both prevention and treatment of this painful condition. It works at the epithelial level to help protect cells in the mouth and throat from the damage caused by chemotherapy and radiation, and to stimulate growth and development of new epithelial cells to build up the mucosal barrier. In the pivotal clinical trial, palifermin reduced the incidence, severity, and duration of severe OM. Palifermin was also well-tolerated; common adverse reactions reported included rash, pruritus, erythema, edema, pain, fever, arthralgia, mouth or tongue disorders, and taste alteration. In this article, nurses who are skilled in caring for patients undergoing HSCT review their clinical experience with palifermin, sharing practical advice about its reconstitution, dosing, and administration. By familiarising themselves with the use of palifermin, nurses can influence a shift in clinical practice away from OM symptom management to the more satisfactory situation of protecting patients against severe OM.
Topics: Fibroblast Growth Factor 7; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Mucositis; Oncology Nursing; Treatment Outcome
PubMed: 17540295
DOI: 10.1016/S1462-3889(07)70004-2 -
Clinical applications of palifermin: amelioration of oral mucositis and other potential indications.Journal of Cellular and Molecular... Nov 2013Mucositis 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... (Review)
Review
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.
Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Chemoradiotherapy; Clinical Trials as Topic; Deglutition Disorders; Fibroblast Growth Factor 7; Head and Neck Neoplasms; Humans; Lung Neoplasms; Stomatitis; Treatment Outcome
PubMed: 24251854
DOI: 10.1111/jcmm.12169 -
Journal of Oncology Pharmacy Practice :... Sep 2005To provide a comprehensive review of the clinical use of the recombinant biological agent, palifermin, with particular reference to its use in its approved indication,... (Review)
Review
OBJECTIVE
To provide a comprehensive review of the clinical use of the recombinant biological agent, palifermin, with particular reference to its use in its approved indication, oral mucositis resulting from high dose chemotherapy and radiation in patients with hematologic malignancies requiring hematopoietic stem cell support.
DATA SOURCES
A MEDLINE search was conducted using the terms 'palifermin' and 'Kepivance.' All data available from MEDLINE were reviewed. The reference lists from retrieved articles were reviewed and other relevant papers were identified.
DATA SUMMARY
Keratinocyte growth factor (KGF) is a growth factor that acts specifically on epithelial cells playing a role in proliferation, migration, and morphogenesis. Palifermin is a recombinant human form of KGF. Because of its ability to cause proliferation of the oral mucosa and to protect against mucosal injury, palifermin is a treatment option for patients who are at high risk for oral mucositis, specifically patients with hematological malignancies receiving stem cell transplantation (SCT). In a phase III study of these patients, the overall incidence of World Health Organization (WHO) grade 3 or 4 oral mucositis was significantly reduced in the palifermin group (palifermin = 63% versus placebo = 98%, P < 0.001). Among the patients who experienced WHO grade 3 or 4 oral mucositis the average duration of this grade of mucositis in the palifermin group was six days compared with nine days in the placebo group (P < 0.001). Common adverse effects of palifermin include pruritus, erythema, mouth and tongue disorders, and taste alterations.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Fibroblast Growth Factor 7; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Recombinant Proteins; Stomatitis
PubMed: 16390600
DOI: 10.1191/1078155205jp159oa