Effects of Palifermin on Antitumor Activity of Chemotherapeutic and Biological Agents in Human Head and Neck and Colorectal Carcinoma Xenograft Models

Abstract

Damage to the gastrointestinal mucosa is a common dose-limiting toxicity of several anticancer therapies. Until recently, adequate control of oral mucositis was considered a significant unmet medical need, with most available treatments providing only palliative benefits without protecting the gastrointestinal epithelium from the damaging effects of cancer therapy. In 2005, palifermin [recombinant human keratinocyte growth factor (KGF)] was approved to decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving myelotoxic therapy requiring hematopoietic stem cell support. Current trials are investigating the use of palifermin in solid tumor settings. The objective of this study was to determine whether combining palifermin with different chemotherapeutic or biological agents affected the antitumor activity of these agents in human head and neck (FaDu) and colorectal (HT29) carcinoma xenograft models. Nude CD1 mice were injected with 1 Â 10 7 of either FaDu or HT29 cells, which express both KGF and epithelial growth factor receptors. Animals were treated with palifermin in various combinations with chemotherapeutic (5-fluorouracil and cisplatin) and/or biological (bevacizumab, cetuximab, and panitumumab) agents. Palifermin alone had no effect on either FaDu or HT29 tumor growth. Palifermin did not affect the therapeutic efficacy of 5-fluorouracil, cisplatin, cetuximab, bevacizumab, or panitumumab in any of the two-or three-way drug combinations tested in either model. The results of this study showed that palifermin did not promote the growth of two carcinoma cell lines that express functional KGF receptors and did not protect these tumor cells from the antitumor effects of several chemotherapeutic and biological agents.

Licochalcone-A induces intrinsic and extrinsic apoptosis via ERK1/2 and p38 phosphorylation-mediated TRAIL expression in head and neck squamous carcinoma FaDu cells

“…Five-week-old male nude mice, each weighing approximately 20 g, were divided into a xenografted positive control group ( n = 5) and xenografted experimental group ( n = 5) in which the anticarcinogenic effect of Lico-A was tested. According to the previously reported method to generate the xenograft animal model with FaDu squamous cell carcinoma (Brake et al, 2008), cells at a concentration of 1 × 10 7 cells/100 µL were injected subcutaneously into the right and left flanks of each of the control and experimental mice, respectively. After tumor formation (approximately 1,000 mm 3 ) was detected under the skin of mice that had received FaDu cell xenographs, 10 mg/kg of Lico-A dissolved in 5% ethanol and 5% ethanol without Lico-A was injected intraperitoneally into experimental and controls groups, respectively, three times per week for 8 consecutive weeks.…”

Efficacy of palifermin (keratinocyte growth factor-1) in the amelioration of oral mucositis

“…While there are no data to support this hypothesis, and xenograft models have demonstrated that palifermin neither stimulates tumor growth nor confers tumor protection from chemotherapy,24 it is imperative that palifermin’s inertia relative to tumor behavior be confirmed if the agent is to be widely accepted by the clinical community.…”

Radioprotective effects of Keratinocyte Growth Factor-1 against irradiation-induced salivary gland hypofunction

“…Keratinocyte growth factor-1 (KGF-1, also known as FGF-7) stimulates the growth of epithelial cells and protects those cells from chemotherapy or radiotherapy-induced oral mucositis. Recombinant KGF (Palifermin) has been approved as a cytoprotective drug to reduce the symptoms of oral mucositis [7, 8]. KGF-1 also has potential for amelioration of irradiation-induced salivary hypofunction [5, 6].…”