Palifermin Group Research Articles

Palifermin Compared to Supersaturated Calcium Phosphate Rinse in Prevention of Severe Oral Mucositis after Stem Cell Transplantation in Patients Receiving Radiotherapy-Based Myeloablative Conditioning

Purpose: Oral mucositis (OM) is a common, debilitating complication of conditioning regimens for hematopoietic stem cell transplantation (HSCT). Supersaturated calcium phosphate rinse (SCPR) and palifermin have shown efficacy in preventing severe OM. However, whether their efficacy differs is unknown. We aimed to compare the efficacy of SCPR and palifermin in HSCT patients receiving myeloablative conditioning. Methods: A comprehensive review of our institutional database was performed to identify patients who received myeloablative-conditioning therapy over 5 years. All HSCT patients who received radiotherapy-based myeloablative conditioning and received either palifermin or SCPR within the study period were included. Most patients received Fludarabine, Busulfan, and total body irradiation (FBT). Patients were divided into two groups based on the OM prophylactic agent received. The primary outcome is prevalence of severe OM (WHO Grade 3 and 4). The secondary outcomes are a prevalence of all-grade OM and WHO Grade 4 OM. These outcomes were compared between the two groups. Results: We identified 26 patients who received SCPR and 122 patients who received palifermin for OM prophylaxis. The prevalence of World Health Organization (WHO) Grade 3 or 4 OM was significantly lower in the palifermin group (57% vs. 100%, p = 0.01). In addition, the palifermin group had lower WHO Grade 4 OM (22% vs. 62%, p = 0.0006). The overall prevalence of OM was not significantly different between the two groups (86% for palifermin group vs. 100% for SCPR arm, p = 0.15). Subgroup analyses demonstrated improved outcomes with palifermin, regardless of age, sex, disease status, donor type, and primary diagnosis. Conclusion: When compared to SCPR, the use of palifermin is associated reduced severity of OM in HSCT patients receiving radiotherapy-based myeloablative conditioning.

Effect of Keratinocyte Growth Factor on Hospital Readmission and Regimen-Related Toxicities after Autologous Hematopoietic Cell Transplantation for Lymphoma

Regimen-related toxicities with high-dose therapy followed by hematopoietic cell rescue leads to considerable patient distress, morbidity, and high readmission rates. Palifermin is a recombinant keratinocyte growth factor that is Food and Drug Administration-approved to decrease severe oral mucositis (OM) associated with autologous hematopoietic cell transplantation (ASCT) for hematologic malignancies. We added palifermin as a supportive care measure for patients with lymphoma undergoing ASCT with BEAM conditioning. We compared patients receiving palifermin (n = 35) with historical controls (n = 38) for toxicity and readmission outcomes. The cumulative incidence of OM of any grade was 23% in the palifermin-treated patients and 42% in the control group. Patients receiving palifermin were less likely to be readmitted (57% versus 82%; P = .04), had fewer hospital readmission days (median, 4 days versus 7 days; P < .01), and had fewer total days in the hospital through day +30 after ASCT (median, 12 days versus 15 days; P = .05). Fewer patients in the palifermin group had >20 days in the hospital through day +30 (9% in the palifermin group versus 23% of controls). Adverse events associated with palifermin were mild and transient. The addition of palifermin limits severe regimen-related toxicities and decreases readmissions and duration of hospital stay. This and other measures are needed to identify comprehensive and cost-effective approaches, possibly including palifermin, to prevent severe regimen-related toxicities and decrease health care resource utilization.

The Efficacy of Palifermin on Oral Mucositis and acute GVHD after Hematopoietic Stem Cell Transplantation in Hematologic Malignancy Patients: A Systematic Review and Meta-analysis study

Oral mucositis (OM) is one of the most common side effects after hematopoietic stem cell transplantation (HSCT) and palifermin is used for prophylactic use to prevent OM. We conducted a meta-analysis study that evaluates the efficacy of palifermin on OM after HSCT in hematologic malignancy patients. Databases of PubMed/Medline, Web of Science and Cochrane Library for English-language publications were searched for finding the relevant studies. The RevMan 5.3 software with random-effects models (odds ratio (ORs) and 95% confidence intervals (CIs)) was used for to estimate of the efficacy of palifermin in palifermin group compared with control group. Begg's and Egger's tests were used for assessment of bias between the studies. Ten studies were included in the meta-analysis study. The results of the meta-analyses showed that there were significant differences in OM (grade 1-4) [odds ratio (OR) = 0.17; 95%CI= 0.10,0.29; p &lt;0.00001], OM (grade 2-4) [OR= 0.11; 95%CI= 0.05,0.24; p &lt;0.00001], OM (grade 3-4) [OR= 0.22; 95%CI= 0.15,0.33; p &lt;0.00001], after auto-HSCT for OM (grade 1-4) [OR= 0.13; 95%CI= 0.04, 0.35; p &lt;0.0001], OM (grade 2-4) [OR= 0.03; 95%CI= 0.00, 0.21; p =0.0006] or OM (grade 3-4) [OR= 0.25; 95%CI= 0.13, 0.48; p &lt;0.0001], after allo-HSCT for OM (grade 1-4) [OR= 0.23; 95%CI= 0.11, 0.51; p =0.0002], OM (grade 2-4) [OR= 0.14; 95%CI= 0.03, 0.74; p =0.012] or OM (grade 3-4) [OR= 0.19; 95%CI= 0.08, 0.46; p =0.0002] and fever [OR=0.51; 95%CI=0.29, 0.87; p = 0.01], but there were no significant differences in acute graft versus host disease (aGVHD) grades, infection and blood stream infection between two groups. The meta-analysis showed that palifermin was associated with reductions in the incidence and severity of OM and also was effective and safe on OM after allo- or auto-HSCT, but did not seem to effect on the incidence and severity of aGVHD.&#x0D; &#x0D; Peer Review Details&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Peer review method: Single-Blind (Peer-reviewers: 02) Peer-review policy &#x0D; Plagiarism software screening?: Yes&#x0D; Date of Original Submission: 01 September 2017&#x0D; Date accepted: 02 October 2017&#x0D; Peer reviewers approved by: Dr. Lili Hami &#x0D; Editor who approved publication: Dr. Phuc Van Pham&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Efficacy of palifermin on oral mucositis and acute GVHD after hematopoietic stem cell transplantation (HSCT) in hematology malignancy patients: a meta-analysis of trials.

Aim of the studyHerein, this meta-analysis study evaluated the efficacy of palifermin after HSCT on the incidence and severity of OM or aGVHD in hematologic malignancy patients in randomized clinical trials (RCTs).Materials and methodsTo compare the efficacy of palifermin on adverse events, OM and aGVHD compared with placebo, we searched databases of PubMed/Medline, Web of Science and Cochrane Library for RCTs based on a number of criteria.ResultsThere was no difference observed in the incidence of OM and aGVHD between two groups. The subgroup analysis didn’t show significant differences in two groups for aGVHD grade 2–4 (odds ratio [OR] = 1.54, 95% confidence interval (CI): 0.70–3.39, p = 0.28), aGVHD grade 3–4 (OR = 0.97, 95% CI: 0.48–1.94, p = 0.92), OM grade 2–4 (OR = 0.76, 95% CI: 0.42–1.38, p = 0.37) and OM grade 3–4 (OR = 0.54, 95% CI: 0.25–1.15, p = 0.11], but erythema as an adverse effect in palifermin group was higher than placebo group (OR = 1.86, 95% CI: 1.10–3.15, p = 0.02].ConclusionsThis meta-analysis of six clinical trials found no statistically significant difference in OM and aGVHD grades in patients receiving 60 μg/kg/day dose of palifermin compared with those receiving a placebo. However, oral mucosal erythema was more prevalent among patients receiving palifermin than patients receiving a placebo.

Efficacy of keratinocyte growth factor (palifermin) for the treatment of caustic esophageal burns.

Current treatment strategies against the development of corrosive esophageal strictures remain unsatisfactory. Thus, the aim of the present study was to investigate the efficacy of keratinocyte growth factor, in the form of palifermin, for the prevention of stricture development following esophageal caustic injuries in a rat model. A total of 32 female Wistar albino rats were divided into four groups, which included the control (C), burn (B), steroid (S) and steroid plus palifermin (S/P) groups. An experimental corrosive esophageal burn model was established in the B, S and S/P groups. Weight gain was recorded and histopathological evaluation was performed for each group. Weight gain in the S and B groups was compared with the control group and statistically significant differences were observed. In addition, statistically significant differences in weight gain were observed between the S/P group and the B group. Histopathologically, statistically significant differences were identified with regard to submucosal collagen deposition, muscularis mucosa and tunica muscularis damage when comparing the B group with the C group. In addition, statistically significant differences were observed when comparing the S and S/P groups with the B group. Furthermore, significant submucosal collagen deposition and tunica muscularis damage were observed in the S group when compared with the S/P group. The stenosis indexes in the C and S groups were significantly lower compared with the B group. In addition, the stenosis index in the S/P group was significantly lower compared with the S group. To the best of our knowledge, the present study is the first to investigate the effect of palifermin on corrosive esophageal burns. The addition of palifermin to the corrosive esophageal burn standard treatment regimen was found to reduce the degree of fibrosis and ameliorate histopathological damage in an experimental model of corrosive esophagitis in rats.

Microbiology in Patients Undergoing Stem Cell Transplantation in the First Year of a Tertiary Care Comprehensive Cancer Centre From India

s / Biol Blood Marrow Transplant 19 (2013) S257eS278 S269 irradiation (TBI) or etoposide (VP16) have been reported in the literature, but a few cases have been reported with palifermin. Objective: To determine the incidence, onset, duration, severity and risk factors for HFS in patients receiving TBI/ VP16 palifermin, and to evaluate the effects of palifermin on the development of HFS. Method: An institutional review board-approved retrospective cohort study of adult allogeneic HSCT patients at City of Hope receiving TBI/VP16 (control) and TBI/VP16/palifermin (palifermin) was conducted during 2 specific time periods. The occurrence of HFS was determined through review of medical records. Results: Incidence of HFS was 38% and 40% in the control (n1⁄458) and palifermin (n1⁄458) groups (Fisher's exact, P1⁄4 .85). Mean duration of HFS was 16.8 and 11 days (t-test, P 1⁄4 .015). Mean onset of HFS occurred on day +7.6 and +3.7 (t-test, P 1⁄4 .0001). SevereHFSoccurred in43%and13% (Fisher's exact, P1⁄4 .07). Severity of HFS was associated with duration in the palifermin group (Spearman r1⁄40.85, P < .0001). Females and patients who developed early skin reactions to palifermin weremore likely todevelopHFS (Fisher's exact,P1⁄4 .01 andP1⁄4 .04). Age, donor type, and palifermin dosing schedule were not risk factors for development of HFS. Conclusion: TBI/VP16 was associated with a 38-40% incidence of HFS. Palifermin significantly reduced time to onset and decreased duration of HFS and offers a previously unreported benefit in this patient population. Female gender and early skin reaction to palifermin were risk factors for HFS.

Peritransplant palifermin use and lymphocyte recovery after T-cell replete, matched related allogeneic hematopoietic cell transplantation

Peritransplant palifermin use and lymphocyte recovery after T-cell replete, matched related allogeneic hematopoietic cell transplantation

Palifermin does not influence the incidence and severity of GvHD nor long-term survival of patients with hematological diseases undergoing HSCT

Palifermin is known as the effective growth factor to reduce the incidence, duration and severity of oral mucositis (OM) following hematopoietic stem cell transplantation (HSCT). However, additional data on the long-term safety of palifermin and its potential influence on graft versus host disease (GvHD) are needed. In this multi-center, non-randomized, matched-control study we assessed early overall survival (OS), incidence and severity of acute/chronic GvHD (a/cGvHD) and incidence of secondary malignancies in 36 patients with hematological diseases treated with allogeneic HSCT and palifermin. The incidence of aGvHD was 28.2% and 38.4% (p=0.34) and cGvHD 41% and 53.8% (p=0.70) in the palifermin and control groups, respectively. The incidence of aGvHD grade 0-IV was 69.2%, 5.1%, 17.9%, 2.5%, 2.5% in the palifermin group and 61.5%, 12.8%, 12.8%, 10.2%, 5.2% in the control group, respectively (p>0.4 for each). The incidence of limited and extensive cGvHD was 17.9% and 23% in the palifermin versus 25.6% and 28.2% in the control group (p=0.32 and p=0.50, respectively). The estimated 3-year OS did not differ significantly between studied groups. We did not observe any secondary malignancies in these patients. Administration of palifermin doesn't seem to influence the incidence and severity of aGvHD/cGvHD, secondary malignancies occurrence and early OS in patients undergoing allogeneic HSCT.

Randomized Controlled Trial of Two Different Dosing Regimens of Palifermin to Prevent Mucositis In Multiple Myeloma Patients Receiving One-Day Administration of High-Dose Melphalan

AbstractAbstract 904Palifermin administered pre and post radiochemotherapy conditioning has previously been shown to significantly reduce the incidence and duration of severe oral mucositis (OM) in patients undergoing autologous stem cell transplantation (ASCT). This randomized clinical trial (RCT) aimed to study the efficacy and safety of palifermin when administered in two different dosing regimens in a chemotherapy-only conditioning setting.The efficacy of palifermin relative to placebo was investigated with palifermin given either pre/post high-dose melphalan (HDM) or pre HDM only in patients with multiple myeloma (MM) undergoing ASCT. Assessment of oral mucositis was primarily based on WHO grades (0/1, 2, 3 or 4) and safety primarily on adverse event (AE) reporting.281 patients (mean age 56 ± 8 years) were enrolled at 39 centers; 224 patients were randomized to receive palifermin and 57 patients to receive placebo. In the palifermin group, 109 patients were randomized to the pre-only arm, receiving palifermin (60 μg/kg/day) iv for 3 consecutive days before HDM and 115 subjects were randomized to the pre/post arm receiving palifermin on 3 consecutive days before HDM and again on 3 consecutive days after ASCT. The number of subjects actually receiving study drug in the these two arms was 109 and 111, respectively. Assessments of OM and safety were made daily until 32 days post transplant or hospital discharge.There was no difference in maximum severity of OM between placebo and palifermin administered pre/post HDM (odds ratio: 0.7 [CI: 0.4, 1.3]) or pre HDM (odds ratio: 1.2 [CI: 0.6, 2.4]). Severe OM (WHO grade 3 and 4) occurred in 37% (placebo), 38% (pre/post-HDM) and 24% (pre-HDM) of the patients. A total of 275 patients (99.3%) experienced at least 1 AE during the study. There were more serious AEs and AEs reported as treatment related by the investigators for patients in the pre/post HDM arm, and less in the pre-HDM arm but still more than in the placebo arm.Overall, no statistically significant differences were observed between placebo and either the palifermin pre-post HDM arm or pre-only HDM arm for maximum severity of OM in this clinical setting with a chemotherapy conditioning regimen of short duration and a comparably low incidence of severe oral mucositis. The pre-only group, however, showed a numerically better result than placebo for the primary and most of the secondary efficacy endpoints. Patients treated with palifermin in the pre HDM arm experienced a more favorable safety profile than the pre/post HDM arm. Possible explanations for the apparent discrepancy compared to previously published trials might be differences in high dose chemotherapy and/or the shorter time interval between the pre and post doses in this study. The impact of the timing of the palifermin post-dose in relation to the pre-dose and in relation to the onset of manifest OM and pathogenesis thus needs to be further explored. Disclosures:Blijlevens:Biovitrum: Consultancy. de Chateau:Biovitrum : Employment. Lissmats:Biovitrum: Employment. Niederwieser:Biovitrum: Consultancy.

Single-Dose Palifermin Prevents Severe Oral Mucositis During Multicycle Chemotherapy in Patients With Cancer

Mucositis can be a serious complication of cancer treatment. Palifermin reduces mucositis when given in multiple doses to patients undergoing hematopoietic stem-cell transplantation. To evaluate the efficacy of palifermin given as a single dose before each cycle in patients receiving multicycle chemotherapy. Randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00267046) The University of Texas M.D. Anderson Cancer Center, Houston, Texas. 48 patients with sarcoma were randomly assigned in a 2:1 ratio to receive palifermin or placebo. All patients received doxorubicin-based chemotherapy (90 mg per m(2) of body surface area over 3 days, by infusion). Palifermin (180 µg per kg of body weight) or placebo was administered intravenously as a single dose 3 days before each chemotherapy cycle (maximum, 6 cycles). Patients who had severe mucositis received open-label palifermin in subsequent cycles. Oral assessment of mucositis by using World Health Organization (WHO) oral toxicity scale (grades 0 to 4), with moderate to severe mucositis (grades 2 to 4) as the main outcomes; patient-reported outcome questionnaire; and daily symptom record diary. A median of 6 blinded cycles (range, 1 to 6) were completed by the palifermin group and 2 (range, 1 to 6) by the placebo group. Compared with placebo, palifermin reduced the cumulative incidence of moderate to severe (grade 2 or higher) mucositis (44% vs. 88%; P < 0.001; difference, -44 percentage points [95% CI, -71 to -16 percentage points) and severe (grade 3 or 4) mucositis (13% vs. 51%; P = 0.002; difference, -38 percentage points [CI, -67 to -9 percentage points]). The main adverse effects were thickening of oral mucosa (72% in the palifermin group vs. 31% in the placebo group; P = 0.007) and altered taste. Seven of the 8 patients who had severe mucositis in the placebo group received open-label palifermin. None of these patients had severe mucositis in the subsequent cycles (a total of 17) with open-label palifermin. Study limitations include smaller sample size for the control group, inclusion of only patients with sarcoma, and perceived unblinding of the treatment because of notable differences between the biologic effects of palifermin and placebo. A single dose of palifermin before each cycle reduced the incidence and severity of mucositis. The drug was generally well tolerated, but most patients experienced thickening of oral mucosa. Further investigation is needed to determine whether palifermin use will facilitate greater adherence to chemotherapy regimens by reducing mucositis.

A 3-day short course of palifermin before HDT reduces toxicity and need for supportive care after autologous blood stem-cell transplantation in patients with multiple myeloma

BackgroundWe retrospectively determined whether a 3-day short course of palifermin could reduce the toxicity of high-dose therapy (HDT) and autologous blood stem-cell transplantation (ASCT) in patients with multiple myeloma (MM). Patients and methodsSixty-seven consecutive patients received 60 μg/kg palifermin for 3 days before HDT with melphalan 200 or 140 mg/m2 for patients with renal failure (group A). Granulocyte colony-stimulating factor (G-CSF) was applied after ASCT. Data on haematopoietic reconstitution and toxicity were compared with two previously published patient groups from our institution who had received pegfilgrastim but not palifermin (group B, n = 21) and patients who had received neither palifermin nor G-CSF (group C, n = 21). ResultsIn group A, patients with renal failure had a significantly higher risk for severe mucositis (64% versus 16%, P < 0.002). Patients with normal renal function who received palifermin experienced significantly less days of hospitalisation (P < 0.05) and less need for narcotic analgesia (P < 0.05), parenteral nutrition (P < 0.05) and erythrocyte transfusions (P < 0.05) in comparison with groups B and C. Time to haematopoietic reconstitution was not compromised by the use of palifermin. ConclusionsIn conclusion, a short 3-day course of palifermin may be able to reduce the toxicity of HDT and ASCT in patients with MM. Patients with impaired renal function at the time of HDT need additional strategies to further reduce the incidence of severe mucositis.

Palifermin Does Not Influence the Incidence and Severity of GvHD Nor Long-Term Survival of Patients with Hematological Diseases Undergoing HSCT

AIMS: Oral mucositis (OM) is a frequent complication of myeloablative therapy and hematopoietic stem cell transplantation (HSCT). Palifermin was found to reduce the incidence, duration and severity of OM induced by high-dose chemotherapy with HSCT (Bone Marrow Transplant. 2007; 40:983–8). However, additional data on the long-term safety of palifermin and its potential influence on graft versus host disease (GvHD) were missing. In this multi-center, non-randomized, matched-control study we assessed overall survival (OS), incidence and severity of acute/chronicGvHD (a/cGvHD) and incidence of secondary malignancies in patients with hematological diseases treated with HSCT who received palifermin as a prophylaxis for OM.METHODS AND RESULTS: One hundred and twenty patients with hematological diseases transplanted between December 2001 and December 2007 were enrolled to this study. Sixty patients (50%) received palifermin (60μg/kg/day) for three consecutive days before and after conditioning therapy (palifermin group). Median age of patients was 37.5 years (range, 19 to 63) in the palifermin group and 35.5 years (range, 18 to 64) in the control group. There were no statistical differences between studied groups in terms of other clinical characteristics, including gender, diagnosis, type of transplant, conditioning regimens or GvHD prophylaxis. Kaplan-Meier curves for OS were calculated and compared using the log-rank test. Fisher's exact and the χ2 trend tests were applied for the analysis of the GvHD data. Twenty one (35%) autologous and thirty nine (65%) allogeneic HSCT (HLA-matched related and unrelated) were performed in each group. Following allogeneic HSCT, the incidence of aGvHD grade 1–4 was 28.2% and 38.4% (p=0.34) and cGvHD was 41% and 53.8% (p=0.70) in the palifermin and control groups, respectively. The incidence of aGvHD severity grade 0,I,II,III,IV was 69.2%, 5.1%, 17.9%, 2.5%, 2.5% in the palifermin and 61.5%, 12.8%, 12.8%, 10.2%, 5.2% in the control group, respectively (p>0.4 for each). The incidence of limited and extensive cGvHD was 17.9% and 23% in the palifermin group versus 25.6% and 28.2% in the control group (p=0.32 and p=0.50, respectively). The estimated 2-years OS (72.8% and 79.8%, respectively) also didn't differ significantly between studied groups (p=0.13). We didn't observe any secondary malignancies in patients enrolled into the study.CONCLUSIONS: Administration of palifermin doesn't seem to influence the incidence and severity of a/cGvHD, secondary malignancies occurrence and OS in patients with hematological diseases undergoing HSCT.

Analysis of the Clinical Impact of the Use of Palifermin in Patients Undergoing Autologous Peripheral Blood Progenitor Cell Transplantation for Multiple Myeloma and Relapsed Lymphoma

Severe mucositis remains a serious complication of autologous PBPC transplantation. Keratinocyte growth factor/KGF (Palifermin) is a 28kd heparin-binding glycoprotein that specifically binds the KGF receptor resulting in a range of biological events including increased mucosal epithelial thickness. Administration of palifermin to patients undergoing TBI-based autologous PBPC transplantation has been shown to reduce the incidence and duration of severe mucositis. In the current study we retrospectively evaluated the use of palifermin in patients with myeloma and relapsed lymphoma undergoing non-TBI autologous PBPC transplantation with high-dose melphalan and BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning regimens respectively. Palifermin was given at a dose of 60 mcg/kg/day on days −5 to −3 in patients with myeloma, days −10 to −8 in patients with lymphoma, and days 0 to +2 in all patients. Depending on clinical status and distance from our centre, patients had the opportunity of early discharge on day +1 with outpatient follow-up. G-CSF was administered (5 mcg/kg/day) starting on day +5 in all patients. Of a total of 81 patients, 32 patients received palifermin (23 myeloma, 9 lymphoma) and were compared to a concurrent non-palifermin treated population of 49 patients (27 myeloma, 22 lymphoma). Patients were comparable with respect to age (overall mean 54.5 years), except that patients with myeloma receiving palifermin were slightly older (mean 60 vs. 55 y, p=0.04), and the numbers of infused CD34 positive cells per kg were similar. There were 46 male and 35 female patients. Administration of palifermin was safe and generally well tolerated with 97% of patients receiving all scheduled doses; rash was seen in 32% of cases. The use of palifermin did not influence engraftment of leukocytes or platelets in either myeloma or lymphoma patients. Analysis of length of stay (LOS) following reinfusion in the entire group suggested a difference of 2 days favouring the palifermin group (mean 11.8 vs 13.8 days), but this was not statistically significantly different. There were also no statistically detectable differences in LOS in palifermin treated or untreated patients with myeloma (mean 13.5 vs 10.5 days) or lymphoma (mean 7.7 vs 17.9 days) respectively, although the number of patients with lymphoma receiving palifermin was small. Patients with myeloma appeared to have higher rates of significant mucositis compared with lymphoma (74% vs 48%, p=0.03) but this was not significant in an exploratory logistic regression analysis when age, gender, underlying disease, administration of palifermin and infused number of PBPC were included in the analysis. We conclude that palifermin can be safely administered to patients undergoing non-TBI high dose therapy and autologous PBPC transplantation. Although there was a suggestion of some improvements in LOS with palifermin, the small numbers of patients limit the strength of such conclusions. Further prospective studies in non-TBI conditioning regimens will help to further define the potential benefits of palifermin in reducing mucositis and its consequences.

Palifermin reduces incidence and severity of oral mucositis in allogeneic stem-cell transplant recipients

In this multicenter study, 30 patients undergoing matched related or unrelated allogeneic stem-cell transplantation for leukemia were treated with palifermin, and retrospectively compared to a matched control group. Palifermin recipients transplanted with an unrelated donor showed a significant reduction of severity, incidence and duration of oral mucositis WHO grades 2-4. In addition, in the palifermin group the use of opioid analgesics and the duration of total parenteral nutrition decreased, whether stem cells were used from matched related or unrelated donors. No beneficial influence of palifermin on the incidence and severity of acute GVHD (aGVHD) was apparent. The incidence and duration of febrile neutropenia, documented infections, hematopoietic recovery or overall survival remained unchanged. The most common adverse effects included rash or erythema, generally mild and transient in appearance. Thus, the administration of palifermin was generally well tolerated and safe, and significantly reduced oral mucositis whereas--regardless of donor status--no effect on the incidence and severity of aGVHD was seen.

Phase II Study of Palifermin and Concurrent Chemoradiation in Head and Neck Squamous Cell Carcinoma

Acute mucositis is a dose-limiting toxicity of concurrent chemoradiotherapy regimens for locally advanced head and neck cancer. Palifermin (a recombinant human keratinocyte growth factor; DeltaN23-KGF) stimulates the proliferation and differentiation of mucosal epithelium to reduce mucositis in patients receiving intensive therapy for hematologic cancers. This study assessed the efficacy and safety of palifermin in patients receiving concurrent chemoradiotherapy for advanced head and neck squamous cell carcinoma. In a phase II trial, standard radiotherapy was delivered in daily 2-Gy fractions to 70 Gy, or hyperfractionated radiotherapy was delivered in 1.25-Gy fractions twice daily to 72 Gy, over 7 weeks. Chemotherapy included cisplatin 20 mg/m(2) for 4 days and continuous-infusion fluorouracil 1,000 mg/m(2)/d for 4 days on weeks 1 and 5 of irradiation. Patients were randomly assigned 2:1 to palifermin 60 microg/kg or placebo once weekly for 10 doses. A follow-up trial evaluated long-term survival. Sixty-seven patients received palifermin and 32 received placebo. The median duration of grade >or= 2 mucositis was 6.5 and 8.1 weeks in the palifermin and placebo groups, respectively (P = .157). Palifermin appeared to reduce mucositis, dysphagia, and xerostomia during hyperfractionated radiotherapy (n = 40) but not standard radiation therapy (n = 59). Adverse events were similar between treatment groups. Palifermin did not alter tumor response or survival. Ten once-weekly doses of palifermin at 60 microg/kg were well tolerated. Most patients completed treatment, but palifermin did not reduce the morbidity of concurrent chemotherapy and radiotherapy. Future studies should evaluate higher palifermin doses with longer and more standardized assessment of acute mucositis.

No Difference in Survival or Long-Term Disease Outcomes in Palifermin-Treated Patients with Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplantation.

Background: Oral mucositis is an adverse effect of myeloablative therapy which has serious clinical and economic consequences as well as a negative impact upon quality of life. The duration and severity of oral mucositis can be reduced by administering palifermin to patients with hematological malignancies receiving myeloablative therapy and undergoing hematopoietic stem cell transplantation (HSCT). However, we still require additional data on the long-term disease outcomes of patients treated with palifermin. Therefore we present here the long-term, safety data for palifermin-treated HSCT patients followed up for approximately 60 months after the last palifermin dose.Methods: The long-term safety data were collected during the follow-up phase of 4 parent trials where patients had received at least one dose of palifermin or placebo. Study assessments included overall survival (OS), progression-free survival (PFS), and secondary malignancies. Assessments were made at 6-month intervals during year 1 and annually thereafter until death or loss to follow-up. Kaplan-Meier curves for overall survival and PFS were calculated and the treatment groups were compared using stratified log-rank test.Results: Altogether 662 patients were randomized to treatment and received either palifermin or placebo (421 palifermin, 241 placebo); 538 patients entered the follow-up study (342 palifermin, 196 placebo). The median follow-up time for patients alive at last visit was 49.8 months (palifermin N=290) and 49.5 months (placebo N=169). There were 131 (32%) and 72 (30%) deaths in the palifermin and placebo groups, respectively. The overall survival curves were similar for both groups (p=0.717). Disease progression occurred in 167 (41%) palifermin- and 87 (36%) placebo-treated patients; the difference in PFS between the two groups was non-significant (p=0.280). Secondary malignancies were observed in 8% of patients in both groups: the incidence of secondary hematologic malignancies was 4% (palifermin: 14/342) versus 5% (placebo: 10/196) while the incidence of solid tumors was 2% in both groups.Conclusion: The results of this 60-month follow-up study indicate that long-term disease outcomes are not affected by administering palifermin to patients with hematological malignancies who are receiving myeloablative therapy and undergoing HS. There was no difference in OS and PFS between the palifermin and placebo groups. Furthermore there was no difference in the incidence of secondary malignancies between the two patient groups. The incidence of secondary hematologic malignancies and solid tumors was low, comparable between groups, and within the expected range for this patient population.

The influence of palifermin (Kepivance) on oral mucositis and acute graft versus host disease in patients with hematological diseases undergoing hematopoietic stem cell transplant

In this multicenter study, we assessed the use of palifermin (recombinant human-keratinocyte growth factor 1) in the prevention of oral mucositis (OM) and acute GvHD (aGvHD) induced by a hematopoietic stem cell transplant (HSCT). Fifty-three patients with hematological diseases received three doses of palifermin (60 mug/kg once daily i.v.) pre- and post-conditioning regimens (total six doses). A retrospective control group of 53 transplant patients received no palifermin. There was a significant reduction in the incidence of OM of WHO (World Health Organization) grades 1-4 (58 vs 94%, P<0.001), 3-4 (13 vs 43%, P<0.001) and the median duration of OM (4 vs 9 days, P<0.001) in the palifermin group compared to the control group. The incidence of analgesics (32 vs 75.5%, P<0.001), opioid analgesics (24 vs 64%, P<0.001) and total parenteral nutrition (11 vs 45%, P<0.001) was also significantly reduced. The analysis of distribution of affected organs revealed that aGvHD was less prevalent in the palifermin group (P=0.036). There was no significant difference in the onset of any OM after HSCT, time to engraftment and length of hospitalization between groups. The drug was generally well tolerated and safe. Our results suggest that the use of palifermin reduces OM and probably aGvHD after HSCT, but a randomized trial is needed.

The Significance of Palifermin (Kepivance) in Reduction of Oral Mucositis (OM) Incidence and Acute Graft Versus Host Disease (aGvHD) in Patients with Hematological Diseases Undergoing HSCT.

AIMS:OM is a frequent complication of the myeloablative therapy and HSCT.In this Polish multi-center study we assessed the ability of palifermin (rHu-KGF1) to reduce the incidence, duration and severity of OM induced by high-dose chemotherapy followed by HSCT in patients with hematological diseases. We also evaluated the requirement for analgesics and total parenteral nutrition (TPN) caused by OM, incidence of febrile neutropenia and severe infections, the influence of palifermin on the engraftment, aGvHD and hospitalization.METHODS AND RESULTS:106 patients with hematological diseases were enrolled to the study.53 of them (50%) received palifermin (60 μg/kg/day) for 3 consecutive days before and after conditioning therapy and they were transplanted between June 2005 and March 2006. Each reporting center submitted equal number of patients to palifermin and control group. Both groups were similar in terms of sex, age, diagnosis, type of transplant and conditioning regimens. The patients in control group were transplanted between December 2000 and 2005.The median age of palifermin and control group was 37,0 years (range, 19 to 58) and 36,1 years (range, 18 to 64), respectively. 29 (54,7 %) autologous and 24 (45,3 %) allogeneic HSCT were performed in both groups. OM was assessed daily after HSCT according to the WHO scale.The incidence of OM of grade 1–4 was 58 % vs 94 % and grade 3–4, 13 % vs 43 % in palifermin group vs. control group, respectively (p<0,001). The median duration of OM grade 1–4 was 4,0 days (range, 0 to 16) in palifermin group and 9,0 days (range, 0 to 28) in control group (p<0,001). As compared with control, palifermin group was also associated with significant reductions in the use of analgesics (32 vs. 75,5 %; p<0,001), opioid analgesics (24 vs. 64 %; p<0,001) and TPN (11 vs. 45 %; p<0,001). Moreover, we observed reduction of the incidence of aGvHD in palifermin group (25 vs.50 %; p=0,03), especially gastrointestinal form (8,3 vs. 29,2 %; p=0,03).No statistically significant differences in the incidence of febrile neutropenia, severe infections and the median duration of hospitalization were observed between groups. Also palifermin did not appear to impair engraftment.The drug was generally well tolerated. Adverse events, mainly rash, pruritus, erythema, generalized edema, mouth/tongue thickness and discoloration and taste alteration were mild to moderate in severity and were transient.CONCLUSIONS: Administration of palifermin significantly reduced the incidence, severity and duration of OM and did not have negative effect on engraftment in the patients with hematological diseases after HSCT. It seems that it could also reduce the incidence of aGvHD, especially gastrointestinal form. It was generally well tolerated and safe.

Acute Enterocolitis Incidence in Patients with Hematological Malignancies Receiving Myelotoxic Therapy Requiring Hematopoietic Stem Cell Support - Palifermin Experience.

Background: Chemotherapeutic agents can cause severe oral and gastrointestinal mucositis, for which there is currently no treatment. Previous research demonstrates that palifermin - keratinocyte growth factor - is potentially antimucotoxic, reducing the duration and severity of oral mucositis after intense chemotherapy in hematological cancers. The primary aim of this study was to determine palifermin effectiveness in ameliorating chemotherapy-induced diarrhoea and oral mucositis incidence. Palifermin adverse events were also assessed.Methods: Retrospective observational study involving patients with hematological malignancies undergoing autologous hematopoietic stem-cell transplantation after myelotoxic therapy. All the patients received antibiotic, antifungal, and antiviral prophylaxis. Patients being treated with palifermin to decrease the incidence and duration of severe oral mucositis (Palifermin Group) were compared to a control group of patients who did not receive palifermin (Control Group). Palifermin was administered during 3 consecutive days, before and after myelotoxic therapy in a 60 μg/Kg daily intravenous dose.Results: Twenty-four patients were included, 8 in Palifermin Group and 16 in Control Group. Baseline malignancies were Hodgkin and non Hodgkin lymphoma, acute myeloid leukemia, and multiple myeloma. All patients underwent autologous hematopoietic stem-cell transplantation after the following conditioning regimes: BEAM, BuCy, and Mel200 respectively. In Palifermin Group, 62.5% were male, mean age 47.6±13.0 years, mean disease duration of 22.3±10.1 months (N=8). In Control Group 56.3% were male, mean age 45.8±12.1 years (N=16). Mean performance status (Karnofsky Index) was 80±14.1% and 71.3±15.1%, in each group, respectively. No statistically significant differences between Palifermin and Control Groups were found regarding the degree of diarrhoea, although in the Palifermin Group the majority of patients presented a grade 2 (N=3) and in the Control Group a grade 3 (N=6). In the Palifermin Group there was a tendency for a lower incidence of hypoalbuminemia [12.5% (Palifermin Group) vs. 50% (Control Group)], which corresponded to a significant lower difference in the needs for receiving parenteral nutrition (P=0.011). Nevertheless, these findings were not translated in less febrile episodes or less iv antibiotic therapy days. There were no significant differences between the two groups regarding the degree of oral mucositis, the number of days of analgesic opioids use, and the number of hospitalization days, most probably due to the small sample considered. The most common adverse events in the Palifermin Group were reversible erythema and edema of the face and upper trunk that have occurred only in 3 patients. Weight increase was mild and similar in both groups of patients [Median weight increase±SD: 1,0±1,7 Kg (Palifermin Group) vs 2,0±2,5 Kg (Control group)].Conclusion: Gastrointestinal and oral mucositis are common consequences of cancer therapy with a direct and significant impact on the quality of life and care costs, also affecting patient's survival. Our exploratory study shows that palifermin treatment is well tolerated, potentially reducing diarrhoea and the incidence of hypoalbuminemia, and significantly reducing the needs for parenteral nutrition. However further studies with an increased number of patients will be necessary to provide more evidence concerning palifermin efficacy in the management of these cancer therapy's debilitating side-effects.

Keratinocyte Growth Factor for Prophylaxis of Oral Mucositis in Children Undergoing Hematopoietic Stem Cell Transplantation.

Oral mucositis (OM) is a frequent and debilitating complication for children undergoing hematopoietic stem cell transplantation (HSCT) that causes significant pain and increases risk of infections or multi-organ failure, and negatively impacts treatment outcomes, patients quality of life and healthcare resources. Palifermin (Keratinocyte Growth Factor, rHuKGF) decreases the incidence and duration of severe mucositis in adult patients receiving HSCT, but so far no data are available on use of Palifermin in children undergoing HSCT. In current study, Palifermin short-term safety and efficacy have been established in pediatric HSCT setting. Methods: A total number of 10 children undergoing HSCT were included into the study. All patients had suffered WHO grade 4 OM during previous chemotherapy. Five children aged 5–16 years were treated with Palifermin: 3 with relapsed ALL had matched-sibling donor allogeneic transplantation, while 2 others with advanced solid tumors (germinal tumor and neuroblastoma) underwent autologous transplantation. Palifermin was administered in the dose 60 μg/kg/day for 3 days prior to conditioning therapy and for 3 days following HSCT. The control group consisted of 5 patients, identified as closely as possible for diagnosis, conditioning, and age, who were included into matched-pair analysis. OM was graded daily according to WHO criteria and evaluated for 28 days after transplantation. All patients were followed-up until day 100 after transplantation. Results: OM WHO grade 4 was not observed in Palifermin group, while 4/5 patients in control group had OM grade 4. The median duration of mucositis of WHO grade ≥3 was 5 days (range, 3 to 8) in the Palifermin group, and 8 days (range, 6–12) in the control group. Opioid analgesic use was not necessary in Palifermin group. None of the patients in Palifermin group had blood-borne bacterial infections nor clinically documented infection. Following allo-HSCT, no patients had acute GVHD>1 in Palifermin group. All patients received total parenteral nutition (TPN) due to loss of appetite. No differences in hematological recovery were observed between groups. Palifermin treatment was associated with improvements in patient-reported outcomes (mouth and throat soreness, swallowing, eating, drinking, taking) and clinical sequelae, including incidence of febrile neutropenia, duration of hospitalization, requirements for parenteral nutrition and well-being. No serious adverse effects were observed in Palifermin group: adverse events, mainly rash, and taste alteration, were mild and transient, while 4/5 patients had white film coating mouth or tongue and taste loss in Palifermin group. Conclusion: Palifermin reduced the duration and severity of OM in pediatric patients after high-dose therapy for HSCT. It appears to reduce the incidence of WHO grade 4 OM and duration of WHO grade 3 or 4 OM and promotes faster mucosal recovery in allogeneic and autologous HSCT recipients. Use of Palifermin for the prevention of severe OM has shown no negative impact on disease outcomes in the HSCT setting for children. The ability of Palifermin therapy to reduce the breakdown of mucosal barrier could decrease the complications caused by systemic infection. Reducing the complications of oral mucositis could decrease the length of hospitalization and serious sequelae.