Palifermin

In plain language

Palifermin is an IV drug used to protect the lining of the mouth during the high-dose chemotherapy that precedes bone marrow transplants in blood cancers, sold as Kepivance. It is a shortened copy of a natural growth factor for skin and mouth cells.

The treatment works by making mouth-lining cells multiply faster, so the tissue regrows between chemotherapy doses. In trials it cut the severe mouth sores that make eating unbearable for transplant patients.

For students

Palifermin is recombinant human keratinocyte growth factor (KGF/FGF7), a 140-residue truncation (about 16.3 kDa) of the 163-residue native protein that retains receptor activity with reduced half-life concerns. KGF signals through FGFR2b (the KGFR splice variant) on epithelial cells, stimulating proliferation and migration of oral, esophageal and gastrointestinal mucosa.

The pivotal randomized placebo-controlled trial (n=212, head and neck cancer and hematologic transplant patients receiving total body irradiation-based conditioning) showed grade 3-4 oral mucositis in 63% of palifermin versus 98% of placebo patients, with a significant reduction in mouth pain, opioid use and total parenteral nutrition days. It is dosed for 3 days before and 3 days after conditioning, and it remains the standard agent for this indication. Because KGF also acts on other epithelia, its use carries a theoretical tumor-promotion caution in epithelial cancers, which is why its use is restricted to the transplant conditioning setting.

For researchers and instructors

Biochemistry. FGFR2b specificity for epithelial (not endothelial or fibroblast) compartments is the structural lesson; recombinant truncation of a growth factor to tune pharmacokinetics is a transferable design principle.

Pharmacology. 60 mcg/kg IV for 6 doses (days -3 to +3 around conditioning); adverse effects include skin rash, oral tingling and taste alteration; no dose adjustment for organ dysfunction.

Human evidence. The pivotal trial (n=212, NEJM 2004, Spielberger et al.) is the classic citation; the subsequent attempt to extend to head and neck radiotherapy failed to meet endpoints, a negative that also teaches.

Teaching point. Teaches epithelial growth factor biology and the concept of prophylactic tissue protection in oncology, as distinct from anti-tumor therapy.