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Plain and simple, the game doesn't seem to like the boss fights (or at least the first one with the helicopter; I haven't gotten any farther). It runs flawlessly otherwise, and just getting to and fighting a boss is no problem at all -- but if I ever die during the fight, the game will inevitably crash with a notification that "prism3d.exe" has encountered a problem. Which I quickly discovered nullifies any changes including savegames (argh) made since you last exited the game.
Thusly I tried getting to the boss and quitting so I could avoid having to redo the entire episode, only to discover that attempting to load a save file saved on the boss stage crashes in the exact same way.
I've tried running the game at varying refresh rates, in D3D and OpenGL, windowed, fullscreen, disabling all hardware acceleration options and putting all settings on their lowest. Same problem.
Running on Windows XP (32-bit).
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Same problem here.
http://www.gog.com/en/forum/duke_nukem_series/prism3d_error
Whoops, not sure how I missed that. Yeah, the fix there doesn't work for me either.