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Key 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 ⁶.)

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.

Glossary Terms

A procedure in which blood-forming stem cells (cells from which all blood cells develop) are removed, stored, and later given back to the same person.

A clinical trial in which the medical staff, the patient, and the people who analyze the results do not know the specific type of treatment the patient receives until after the clinical trial is over.

A disease caused when cells from a donated stem cell graft attack the normal tissue of the transplant patient. Symptoms include jaundice, skin rash or blisters, a dry mouth, or dry eyes. Also called GVHD.

An intensive drug treatment to kill cancer cells, but that also destroys the bone marrow and can cause other severe side effects. High-dose chemotherapy is usually followed by bone marrow or stem cell transplantation to rebuild the bone marrow.

Injection into a vein.

A natural substance that stimulates the growth of epithelial cells in the skin and in the lining of the mouth, stomach, and intestines. A form of keratinocyte growth factor made in the laboratory is called recombinant human keratinocyte growth factor. Also called KGF.

A statistics term. The middle value in a set of measurements.

A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth.

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.