adobe indesign
http://help.adobe.com/en_US/indesign...160F6C65a.html
if you have £350+ to spare.
otherwise
SIGIL for £ zero i.e. for free
or
work in MS office or open office, save in a format that calibre can convert (e.g. RTF, Filtered HTML ) , convert + use sigil just for fine tuning.