You should be putting large files like that on a drive other than your system drive. Sometimes when I can get the drive small enough I copy everything that's left off of it and re-format it by writting zeros to the entire drive. Then I copy whatever I had left back onto it. Sometimes I'm luckyk enough to get all of my jobs done and can just wipe the whole thing.
I don't know if that's something that has to be done, but it's fairly simple so I do it just to be safe.
But in those cases there's no reason to mess with the system drive itself.