Palifermin Reduces Mouth Sores Caused by Blood Cancer TreatmentKey Words
Lymphoma, leukemia, oral mucositis, high-dose chemotherapy, radiation, autologous stem cell transplantation, keratinocyte growth factor. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
An experimental drug called palifermin (Kepivance®) reduced both the severity and the duration of sores and ulcers in the mouth in patients who received intensive chemotherapy and radiation to treat lymphoma and other cancers of the blood, a new study reports.
Source
New England Journal of Medicine, December 16, 2004.
Background
Many cancer patients who undergo treatment with high doses of chemotherapy and radiation develop oral mucositis, or sores and ulcers in the mouth, which can cause severe pain, limit patients' ability to take food and drink by mouth, and lead to severe infections. Pain medications may reduce the discomfort of oral mucositis, but no standard therapy currently exists to prevent or treat this common, potentially serious complication of cancer treatment.
Preliminary studies of an experimental biologic drug called palifermin (Kepivance®) suggested that it was safe and might offer some protection against mouth sores. Palifermin is a laboratory-made, modified version of a naturally occurring human protein called keratinocyte growth factor (KGF). KGF stimulates cells in tissues such as the skin and the surface of the mouth to divide and grow. Animal studies and early-phase clinical trials have shown that palifermin, like natural KGF, also stimulates these cells to divide and grow. The current study was the first completed phase III randomized, double-blind, placebo-controlled trial of palifermin in people.
The Study
This study involved 212 patients with lymphoma and other cancers of the blood who were scheduled to undergo total-body radiation and high-dose chemotherapy followed by autologous stem-cell transplantation.
Patients were assigned at random to receive either palifermin or a placebo intravenously. They received the assigned treatment for three consecutive days before starting total-body radiation therapy. After undergoing transplantation, they received either palifermin or a placebo again for an additional three days.
Specially trained health care workers assessed the patients for mouth sores every day, starting eight days before the transplant and continuing for up to four weeks. Patients also filled out a daily questionnaire, reporting how severe their mouth sores were and how seriously these sores interfered with their ability to eat and to perform other daily activities.
The study was conducted at 13 centers across the United States. Ricardo Spielberger, M.D., of the City of Hope National Medical Center in Duarte, California, led the study team.
Results
Almost all (98 percent) of the patients who received a placebo developed mouth sores so severe that they could not swallow solid food or, in some cases, take any food or drink by mouth. By contrast, 63 percent of patients who received palifermin developed mouth sores of this severity. The condition persisted for a median of nine days in the placebo-treated group compared with a median of six days in the palifermin-treated group.
Patients who received palifermin reported fewer mouth soreness and fewer complications of mouth sores such as difficulty eating, drinking, talking, or sleeping. They also needed fewer painkilling drugs to treat mouth sores and developed fewer serious infections than patients who received a placebo.
On the basis of this study’s results, the U.S. Food and Drug Administration approved palifermin to reduce the incidence and duration of severe oral mucositis in patients with cancers of the blood who receive high doses of chemotherapy and radiation therapy followed by stem cell transplantation.
Limitations
The study was funded by Amgen, Inc., the manufacturer of palifermin.
Because palifermin is a laboratory-made version of a human growth factor (a substance that stimulates cells to divide and grow), it is "theoretically possible" that treatment with palifermin could stimulate the growth of second cancers, the study authors note. Patients who took part in the study are being followed long-term to evaluate whether this risk is real. After 12 months of follow-up, the number of patients surviving without progression of their disease was nearly identical in the palifermin and placebo groups.
Comments
This study's findings support the use of palifermin for the indication that is now FDA-approved: to decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies who receive high doses of chemotherapy and radiation therapy followed by stem cell rescue. Additional clinical trials are now under way to test palifermin's effectiveness at reducing other side effects of cancer treatment, such as swallowing problems associated with chemotherapy and radiation therapy for lung cancer and graft-versus-host disease.
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