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| Frequently Asked Questions |
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What is Kepivance® (palifermin)?
Kepivance® is a human keratinocyte growth factor (KGF). It differs from endogenous human
KGF in that the first 23 N-terminal amino acids have been deleted to improve stability.1
What is the indication for Kepivance®?
Kepivance® is indicated to decrease the incidence and duration of severe oral mucositis
in patients with hematologic malignancies receiving myelotoxic therapy requiring hematopoietic
stem cell support.1 The safety and efficacy of Kepivance® have not been established in patients
with non-hematologic malignancies.1
How does Kepivance® work?
Keratinocyte growth factor (KGF) binds to the KGF receptor, resulting in proliferation,
differentiation, and migration of epithelial cells.1 Kepivance® is a recombinant form of KGF.1
Are there any contraindications to Kepivance®?
Kepivance® is contraindicated in patients with known hypersensitivity to E coli-derived proteins,
palifermin, or any other component of the product.1
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What types of cancers did patients have in registrational clinical trials?
All patients had hematologic malignancies including non-Hodgkin's lymphoma, Hodgkin's disease, acute myeloid
leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, or multiple myeloma.
What was the source of stem cells in clinical trials?
In clinical trials to date, stem cells were harvested from peripheral blood and bone marrow.1,2
What were the conditioning regimens used
in the Kepivance® clinical trials prior to HSCT?
In the phase 2 and 3 clinical trials, patients received
high-dose myeloablative therapy consisting of fractionated total-body irradiation (TBI) (12 Gy total dose), high-dose etoposide (60 mg/kg),
and high-dose cyclophosphamide (100 mg/kg). TBI was delivered before the administration of chemotherapy in 6, 8, or 10
fractions over three or four days, with greater than six hours between fractions. Chemotherapy consisted of high-dose
etoposide, administered on day -4 and one dose of high-dose cyclophosphamide, administered on day -2.1,2
In a phase 1 clinical trial, patients received BEAM, consisting of BCNU 300 mg/m2
IV on day -6, etoposide 200 mg/m2 daily IV and cytosine arabinoside 200 mg/m2 twice daily IV on
days -5, -4, -3, and -2, and melphalan 140 mg/m2 IV on day -1.4,5
In a phase 1 clinical trial involving allogeneic patients, 2 different conditioning regimens were
used depending on the study center. At center 1, patients received cyclophosphamide (60 mcg/kg/day)
on days -7 and -8 and fractionated total-body irradiation (13.2 Gy total dose) on days
-4, -3, -2, and -1. At center 2, patients received busulphan (1 mg/kg/dose) on days -7, -6,
-5, and -4 and cyclophosphamide (60 mg/kg/day) on days -3 and -2.5
In the phase 3 clinical trial, what were the criteria for putting patients on total parenteral nutrition (TPN)?
TPN was given according to the standards of each study site.2
How were patient-reported outcomes evaluated in the phase 3 clinical trial?
Patient-reported outcomes were collected using 5-point scales, with zero representing no soreness or limitation and four representing extreme
soreness or inability to perform the functional activity. Patients completed an oral mucositis questionnaire daily, starting 11 days before transplantation
until 28 days after transplantation. Functional activities evaluated included mouth and throat soreness, eating, drinking, swallowing, and talking.2
Where was the Kepivance® phase 3 clinical trial conducted?
The phase 3 clinical trial was conducted in 13 different centers including2:
- City of Hope National Medical Center, Duarte, CA
- Fred Hutchinson Cancer Research Center, Seattle, WA
- Georgetown University Cancer Center, Washington, DC
- Loyola University Medical Center, Maywood, IL
- Medical College of Virginia, Richmond, VA
- Memorial Sloan Kettering Cancer Center, New York, NY
- Northwest Marrow Transplant Center, Portland, OR
- Sinai Hospital of Baltimore, Baltimore, MD
- SUNY Upstate Medical University, Syracuse, NY
- Texas Transplant Institute, San Antonio, TX
- UCLA Division of Hematology/Oncology, Los Angeles, CA
- University of Minnesota, Minneapolis, MN
- University of North Carolina, Chapel Hill, NC
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Is Kepivance® (palifermin) effective in
reducing the incidence and duration of severe oral mucositis (Grade 3/4)?
Kepivance® is effective in reducing the incidence and duration of severe oral
mucositis in patients with hematologic malignancies receiving myelotoxic therapy
requiring HSCT. In clinical studies, Kepivance® significantly reduced the incidence
of severe oral mucositis (63% vs 98% for placebo; P < 0.001). Kepivance® also significantly
reduced the median duration of severe oral mucositis by 6 days among all patients studied
(3 vs 9 days for placebo; P < 0.001). In the subset of patients who developed severe oral
mucositis, Kepivance® patients experienced 3 fewer days of severe oral mucositis (6 vs 9
days for placebo; P < 0.001) and 4 fewer days of the most severe oral mucositis (Grade 4)
(2 vs 6 days for placebo; P = 0.004).1,2
Did Kepivance® help reduce downstream clinical
consequences of severe oral mucositis?
Kepivance® helped patients continue to perform basic daily activities such as eating, drinking, swallowing,
and talking. Kepivance® also reduced opioid use and total parenteral nutrition (TPN).
Patients receiving Kepivance® required a median of 4 fewer days of opioid analgesics
compared to patients receiving placebo. The cumulative dose required was lower in patients
receiving Kepivance® compared to patients receiving placebo (212 mg of morphine equivalents
vs 535 mg of morphine equivalents; P < 0.001). Kepivance® also reduced the incidence of
TPN by 44% compared to patients receiving placebo (31% vs 55% for placebo; P < 0.001).1,2,6
Is Kepivance® effective in pediatric patients?
The safety and efficacy of Kepivance® in pediatric patients have not been established.1
Were there any differences in the time to
hematopoietic recovery between patients receiving Kepivance® and patients
receiving placebo?
There was no evidence of a delay in the time
to hematopoietic recovery in patients who received Kepivance® as compared
to patients who received placebo.1
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What is the recommended dosing of Kepivance®?
The recommended dosage of Kepivance® is 60 mcg/kg/day, administered as an
IV bolus injection for 3 consecutive days before and 3 consecutive days after
myelotoxic therapy for a total of 6 doses.1
How is Kepivance® administered?
The first three doses should be administered prior to myeloablative therapy,
such that the third dose is administered 24-48 hours before myelotoxic therapy.
The last three doses should be administered after myelotoxic therapy;
the first of these doses should be administered after but on the same day as
hematopoietic stem cell infusion and at least 4 days after the most recent Kepivance® administration.1
Kepivance® should not be administered within 24 hours before, during infusion of, or within
24 hours after administration of myelotoxic chemotherapy. In a clinical
trial, administration of Kepivance® within 24 hours of chemotherapy resulted
in increased severity and duration of oral mucositis.1
Is the fourth dose administered directly
after the HSCT infusion, or can you wait a few hours after?
In the phase 3 clinical study, Kepivance® was administered
within a few minutes to 6 hours after the HSCT infusion.5
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What were the most serious adverse events
reported in the registrational clinical trials of Kepivance®?
In patients with hematologic malignancies, the most common serious adverse reaction in clinical trials
attributed to Kepivance® was skin rash reported in less than 1% of patients.
Grade 3 skin rashes occurred in 3% of patients receiving Kepivance® and 2% of patients
receiving placebo. In seven patients (5 Kepivance®, 2 placebo), study drug was
discontinued due to skin rash.1
Other serious adverse reactions occurred at a similar rate in
patients who received Kepivance® or placebo with the most frequent being fever,
gastrointestinal events, and respiratory events.1
In patients with hematologic malignancies, what were the most frequently reported adverse
events attributed to Kepivance® in the registrational clinical trials?
The most frequently reported adverse reactions attributed to
Kepivance® in registrational trials were rash, erythema, edema, pruritus,
dysesthesia, mouth/tongue thickness or discoloration, and taste alteration.1,2
Most of the side effects were consistent with the pharmacologic action of
Kepivance® on skin and oral epithelium, generally mild to moderate in severity, and reversible.2
Are there any drug interactions with Kepivance®?
No formal drug-drug interaction studies have been conducted for Kepivance®
with drugs that may be used in the intended patient population. Kepivance®
has been shown to bind to heparin in vitro. Therefore, if heparin is
used to maintain an IV line, saline should be used to rinse the line prior to and after
Kepivance® administration.1
Kepivance® should not be administered within 24 hours
before or during infusion of cytotoxic chemotherapy.
In a clinical trial, administration of Kepivance® within 24 hours of
chemotherapy resulted in an increased severity and duration of oral mucositis.1
Did the elevations in serum
amylase and lipase require intervention?
While reversible elevations in serum lipase and amylase
(predominantly salivary in origin) occurred, they did not require
treatment intervention. In general, peak increases were observed
during the period of cytotoxic therapy and returned to baseline
by the day of HSCT infusion.1
Have neutralizing antibodies been detected?
As with all therapeutic proteins, there is potential for immunogenicity.
The clinical significance of antibodies to Kepivance® is unknown but may include
lessened activity and/or cross reactivity with other members of the
fibroblast growth factor (FGF) family of growth factors.1
A sensitive electrochemiluminescence-based binding assay was
performed on post-treatment sera from 645 patients treated with Kepivance®
in clinical studies. Twelve (2%) of these 645 patients tested positive for
antibodies to Kepivance® following treatment. None of the samples
had evidence of neutralizing activity in a cell-based assay.1
The incidence of antibody positivity is highly dependent
on the specific assay and its sensitivity. Additionally, the observed
incidence of antibody positivity in an assay may be influenced by several
factors including sample handling, timing of sample collection, concomitant
medications and underlying disease. For these reasons, comparison of the incidence
of antibodies to Kepivance® with the incidence of antibodies to other products may be misleading.1
Can Kepivance® be given to patients with non-hematologic malignancies?
The safety and efficacy of Kepivance® have not been established in patients with non-hematologic malignancies.
The effects of Kepivance® on stimulation of KGF receptor-expressing, non-hematopoietic tumors in patients are not known.
Kepivance® has been shown to enhance the growth of human epithelial cell lines in pre-clinical (in vitro and in vivo) models.1
| 1 |
(palifermin) prescribing information. |
| 2 |
Spielberger R, Stiff P, Bensinger W, et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med. 2004;351:2590-2598. |
| 3 |
Rubenstein EB, Peterson DE, Schubert M, et al. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer. 2004;100(suppl 9):2026-2046. |
| 4 |
Durrant S, Pico JL, Schmitz N, et al. A phase 1 study of recombinant human keratinocyte growth factor (rHuKGF) in lymphoma patients receiving high-dose chemotherapy (HDC) with autologous peripheral blood progenitor cell transplantation (AUTOPBPCT). Blood. 1999;94:700a. |
| 5 |
Blazar BR, Weisdorf DF, DeFor TE, et al. Palifermin is Safe and
Well-Tolerated in Patients with Hematologic Malignancies Undergoing
High-Dose Chemotherapy Followed by Allogeneic Stem Cell
Transplantation. BB&MT. 2005;11 (2 Suppl 1):4. Abstract #11.
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| 6 |
Spielberger R, Emmanouilides C, Stiff P, et al. Use of recombinant human keratinocyte growth factor (palifermin) can reduce severe oral mucositis in patients with hematologic malignancies undergoing autologous peripheral blood progenitor cell transplantation after radiation-based conditioning. J Support Oncol. 2004;2(suppl 2):73-74. |
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ABOUT ORAL MUCOSITIS
ABOUT KEPIVANCE®
TOOLS AND RESOURCES
FOR NURSES
FOR PHARMACISTS
IMPORTANT PRODUCT SAFETY INFORMATION
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