I had a Murder at the Four Deuces party for my 14th birthday party. (It actually just finished about an hour ago, but it was so amazing that I can't sleep!)
Anyway, about an hour before the party, two people called and told me that they were very sorry, and they couldn't make it. I was totally freaking out at this point, because I didn't have any extra people, and it would be impossible to ask somebody to play two parts. One of my friends however, saved the day by calling somebody totally last minute to fill in. I ended up taking a role myself, even though I had previously read all of the secret sheets to be the host. I just had to pretend that I didn't know who the killer was, etc. It worked out as well as it could've.
The party itself was AMAZING! When everybody arrived, they weren't in character, which was fine, as we just hung out until everybody got there. I read the Hosts Announcement and told people to get started. We had a bit of a rocky start as people immersed themselves in their character...it took about 15-20 minutes for people to really get into it.
Everybody had an amazing time just fooling around and playing their part, although many people made up different twists to the plot and disregarded certain things on their Secrets Sheets. People would sometimes come in and out of their character...if they had a question about who's who or if something funny happened. But it worked out great anyway, we had a few additional murders...some people were even murdered multiple times!
Like I said, we didn't exactly follow the directions PERFECTLY, but in the end, everybody had an amazing time and they were all telling me how much fun they had.
My suggestions? Tell everybody to COME IN CHARACTER, as this will ease the transition and won't make it as difficult as it would be to just say "Okay, now get into your character!" Also, PLAN for one or two people cancelling last minute...have a sibling or a neighbor or just an extra friend who's willing to fill in at the last minute. This will save you a lot of stress and hassle. And also, don't worry too much if people aren't doing things exactly "right", as most of the fun is in DOING the party, not guessing who the murderer was.