Kepivance (palifermin) reduces mouth sores from 5FU chemotherapy for colorectal cancer.

Palifermin (Kepivance®) reduced mouth inflammation and sores (mucositis) during treatment with 5FU and leucovorin for metastatic colon or rectal cancer.  The painful sores can make eating, drinking , and swallowing difficult and can lead to infection and the need to reduce chemotherapy.

Currently, the only proven effective prevention for chemotherapy-induced mucositis is cooling the mouth (cryotherapy) before and during treatment with 5FU.  Patients chew or suck on ice chips or popsicles.

Patients in the study were randomly assigned to either palifermin or a placebo intravenously for three days before each of two chemotherapy treatments .  Thirty-six patients received a placebo and 28 patients were given palifermin during the phase II clinical trial. 

Trial participants had metastatic colon or rectal cancer and were scheduled to receive bolus injections of 5FU (fluorouracil) and leucovorin for a five days in a row every four weeks. (Mayo Clinic Regimen)  Staff members examined their mouths and rated the extent of mucositis from grade 0 (none) to grade 4 where there were mouth sores so severe that eating was not possible at all.  Patients also completed a self-rating scale.

During the first chemotherapy cycle, patients receiving palifermin had half the incidence of grade 2 mucositis (appearance of mouth sores) as did those on placebo — 29% versus 61%.  During the second cycle fewer patients in both groups had grade 2 mucositis — 11% of those on palifermin and 29% of those receiving a placebo. 

However, patients with serious side effects during the first cycle of chemotherapy had their dose of 5FU reduced for the second one.  Fourteen percent of palifermin patients needed a reduced dose for the second cycle compared to 31% of patients on placebo.

Forty-six percent (46%) of patients who received palifermin had no mucositis at all compared to 17% of those on placebo.  No patients in either group experienced the most severe grade 4 mouth sores.

More patients on palifermin experienced an oral side effect (66%) than those on placebo (38%) including dry mouth, a white coating on the tongue, and taste changes. 

Palifermin had no effect on overall survival, time to disease progression, or progression-free survival which were similar for both treatment and placebo groups.  It also did not reduce the incidence of diarrhea.

Lee S. Rosen, M.D. and colleagues reported their results in the Journal of Clinical Oncology, November 20, 2006.  They wrote,

Palifermin is a novel therapeutic that may help reduce the incidence and duration of FU-induced mucositis, potentially allowing for uninterrupted full-dose treatment in patients receiving these chemotherapy
regimens. To date, only cryotherapy has been shown to have some benefit in reducing mucositis (although it has no effect for diarrhea) in patients undergoing FU chemotherapy.

 Palifermin is a laboratory-produced version of a natural protein that stimulates the growth of cells in the skin and the lining of the mouth and gastrointestinal tract called keratinocyte growth factor (KGF). Palifermin is marketed as Kepivance®  It is FDA approved for use in patients with blood cancers who are receiving high dose chemotherapy with stem cell support where severe mucositis is a serious side effect.

The study was supported by Amgen, Inc. who market Kepivance®.