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 x 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.

• Authors: Rachael Brake, Charlie Starnes, John Lu, Danlin Chen, Suijin Yang, Robert Radinsky, Luis Borges
• Journal: Molecular cancer research : MCR (Mol Cancer Res) Vol. 6 Issue 8 Pg. 1337-46 (Aug 2008) ISSN: 1541-7786 [Print] United States
• PMID: 18708365 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Fibroblast Growth Factor 7
• Bevacizumab
• ErbB Receptors
• Receptor, Fibroblast Growth Factor, Type 2
• keratinocyte growth factor receptor
• Cetuximab
• Cisplatin
• Fluorouracil

Topics

• Animals
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (therapeutic use)
• Bevacizumab
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cetuximab
• Cisplatin (pharmacology, therapeutic use)
• Colorectal Neoplasms (drug therapy, genetics, pathology)
• Drug Therapy, Combination
• ErbB Receptors (genetics, metabolism)
• Female
• Fibroblast Growth Factor 7 (pharmacology, therapeutic use)
• Fluorouracil (pharmacology, therapeutic use)
• Gene Expression Regulation, Neoplastic (drug effects)
• Head and Neck Neoplasms (drug therapy, genetics, pathology)
• Humans
• Mice
• Receptor, Fibroblast Growth Factor, Type 2 (genetics, metabolism)
• Xenograft Model Antitumor Assays