A protective role for keratinocyte growth factor in a murine model of chemotherapy and radiotherapy-induced mucositis.
OBJECTIVE
To evaluate the activity of palifermin (rHuKGF) in a murine model of mucosal damage induced by a radiotherapy/chemotherapy (RT/CT) regimen mimicking treatment protocols used in head-and-neck cancer patients.


METHODS
A model of mucosal damage induced by RT/CT was established by injecting female BDF1 mice with cisplatin (10 mg/kg) on Day 1; 5-fluorouracil (40 mg/kg/day) on Days 1-4, and irradiation (5 Gy/day) to the head and neck on Days 1-5. Palifermin was administered subcutaneously on Days -2 to 0 (5 mg/kg/day) and on Day 5 (5 mg/kg). Evaluations included body weight, organ weight, keratinocyte growth factor receptor expression, epithelial thickness, and cellular proliferation.


RESULTS
Initiation of the radiochemotherapeutic regimen resulted in a reduction in body weight in control animals. Palifermin administration suppressed weight loss and resulted in increased organ weight (salivary glands and small intestine), epithelial thickness (esophagus and tongue), and cellular proliferation (tongue and salivary glands).


CONCLUSIONS
Administration of palifermin before RT/CT promotes cell proliferation and increases in epithelial thickness in the oral mucosa, salivary glands, and digestive tract. Palifermin administration before and after RT/CT mitigates weight loss and a trophic effect on the intestinal mucosa and salivary glands, suggesting that palifermin use should be investigated further in the RT/CT settings, in which intestinal mucositis and salivary gland dysfunction are predominant side effects of cytotoxic therapy.
Borges
Luis
L
Departments of Hematology, Cancer Biology, and Pathology, Amgen Inc., Thousand Oaks, CA 91320, USA. borgesl@amgen.com
Rex
Karen L
KL
Chen
Jennifer N
JN
Wei
Ping
P
Kaufman
Stephen
S
Scully
Sheila
S
Pretorius
James K
JK
Farrell
Catherine L
CL
D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000627:therapeutic use*; D006801:Humans; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D019394:Ki-67 Antigen / Q000032:analysis; D051379:Mice; D009055:Mouth / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D011838:Radiation-Sensitizing Agents; D011878:Radiotherapy / Q000009:adverse effects; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism; D013280:Stomatitis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*
D019394:Ki-67 Antigen; D011838:Radiation-Sensitizing Agents; D051523:Fibroblast Growth Factor 7; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor; D002945:Cisplatin