Method: Focusing on the AEs we considered the most difficult to manage (hand-foot skin reaction [HFSR], diarrhoea, fatigue and mucositis/stomatitis), we reviewed the literature to identify strategies relevant to sorafenib. Given the paucity of published work, this included strategies concerning targeted agents in general. This information was supplemented by considering the wider literature relating to management of these AEs in other tumour types and similar toxicities experienced during conventional
anti-cancer therapy. Together with our own experience, this information was used to compile an AE management guide to assist nurses caring selleck screening library for patients receiving sorafenib.
Results: Our collated
experience suggests the most commonly reported AEs with sorafenib and other targeted agents are HFSR, diarrhoea, fatigue, rash and mucositis/stomatitis; these generally have an acute (appearing at similar to 0-1 months) or delayed onset https://www.selleckchem.com/products/JNJ-26481585.html (appearing at similar to 3 months). Most management strategies in the literature were experience-based rather than arising from controlled studies. However, strategies based on controlled studies are available for HFSR and mucositis/stomatitis.
Conclusions: Evidence, especially from controlled studies, is sparse concerning management of AEs associated with sorafenib and other targeted agents in RCC/HCC. However, recommendations can be made based on the literature and clinical experience
that encompasses targeted and conventional therapies, particularly in the case of non-specific toxicities e.g. diarrhoea and fatigue. (C) 2011 Elsevier Ltd. All rights reserved.”
“Among the newer and promising weapons against cancer BMS-345541 purchase are Farnesyl Transferase Inhibitors (FTI). Indeed it is known that the enzyme Farnesyl Transferase (FT), catalyses the prenylation of cysteine residues of several proteins associated with cancer progression, including oncogenic forms of Ras.FTI could alter tumour progression.
Exploration of our corporate structural database, based on concepts of diversity and similarity, brought forward a quinazoline-2,4-dione possessing weak farnesyl transferase inhibitory properties. A systematic modulation of structural parameters allowed the elaboration of a series of analogs out of which the most potent compound (21b) exhibited an IC(50) of 19 nM on FT, an excellent cellular activity on the oncogenic H-Ras-transfected cell line Ras #1, as well as selectivity (ratio of IC(50) on parental RAT2 cells/IC(50) on Ras#1 cells > 2000). Moreover this compound also showed encouraging “”in vivo”" activity. The synthesis of these new chemical entities as well as the structure activity relationships found following pharmacological testing, is described.