Phoenix died of a drug overdose at the age of 23 in 1993 outside the Viper Room nightclub in Hollywood.
Wheaton told ShortList: "Around the time River died I hadn't talked to him for years, so I carry a little bit of guilt.
"But we do what we can and enough time has elapsed now that when I watch [Stand By Me], I recall, with tremendous fondness, the experiences we had shooting it. But honestly, mostly I just enjoy the story."
The 1986 film's director Rob Reiner added: "It's so sad. Every time I see that scene when he disappears at the end of the movie, it's chilling.
"I never thought River was going to be the one who would struggle - he was a good kid and he was so talented. He would've been [like] Johnny Depp or Leonardo DiCaprio. It was such a tragic loss."
> Leonardo DiCaprio: 'River Phoenix was my hero'
> Ledger, Phoenix warned DiCaprio off drugs
Watch the Stand By Me trailer below: