Ferrone, Marcus

Objective: To summarize the pharmacology, development, and clinical application of sorafenib, a specific tyrosine kinase and vascular growth factor inhibitor, for the treatment of renal cell carcinoma (RCC). Data Sources: Clinical literature, including both primary studies and review articles, was obtained by searching MEDLINE (1966–May 2006), using the search terms BAY 43-9006, sorafenib, renal cell carcinoma, and tyrosine kinase inhibitor. Additional information was supplied by the manufacturer, Bayer HealthCare Pharmaceuticals. Study Selection and Data Extraction: Review articles, abstracts, and clinical studies related to sorafenib were analyzed. An evaluation of the research exploring sorafenib as a potential therapy for RCC was conducted. Relevant information was then selected and is reviewed in this article. Data Synthesis: Knowledge of the cellular abnormalities that can cause solid tumors has led to the development of medications that block these pathways. Sorafenib is an oral tyrosine kinase inhibitor that both blocks the Raf kinase pathway and inhibits vascular growth factors. Phase I and II trials have demonstrated that sorafenib has activity against RCC. Dermatologic reactions (rash, desquamation), fatigue, and hypertension have been the most commonly seen treatment-related adverse events. Sorafenib received FDA approval in December 2005 for treatment of advanced RCC. Conclusions: Sorafenib is a novel oral tyrosine kinase inhibitor effective in the treatment of RCC.

Objective: To summarize the pharmacology, development, and clinical application of teduglutide (ALX-0600), a glucagon-like peptide-2 (GLP-2) analog for the treatment of short bowel syndrome (SBS). Data Sources: Clinical literature, including both primary sources and review articles, was accessed through a search of the MEDLINE databases (1980–March 2006). Key search terms included teduglutide, ALX-0600, glucagon-like peptide-2, short bowel syndrome, short gut, and intestinal adaptation. Clinical trial and drug data were supplied by the manufacturer, NPS Pharmaceuticals. Study Selection and Data Extraction: Review articles, abstracts, and clinical studies related to GLP-2 and its analog, teduglutide, were analyzed. An evaluation of the research exploring teduglutide for the management of SBS was conducted. Relevant information was then selected. Data Synthesis: Research has revealed that administration of GLP-2 to patients following major small bowel resection improves intestinal adaptation and nutrient absorption. Teduglutide is an enzyme-resistant GLP-2 analog that shows promise in preventing intestinal injury, restoring mucosal integrity, and enhancing intestinal absorptive function. Conclusions: Data from ongoing clinical trials indicate that teduglutide may have the ability to enhance intestinal absorptive capacity in patients with SBS. Further studies and the completion of Phase III trials are necessary to determine the appropriate dosage and length of treatment for patients with SBS to gain optimal therapeutic benefit from this drug.