As we’ve all recently witnessed, some actors have polished public images but are a mess in real life. After reading two recent papers by groups in Los Angeles and Turkey, it sounds like the same could be said of 5-azacytidine (Vidaza®).
Mounds of clinical data now show that 5-azacytidine is a good treatment for blood cancers, particularly myelodysplastic syndromes (MDS). It gets incorporated into DNA and RNA and inhibits methylation, but researchers still aren’t totally certain why it’s worked better than its predecessors.
In a recent clinical study, researchers at USC wanted to figure out the best dose (Epigenetics 2010). They did this by looking at whether patients got better, but also by looking at the methylation of repetitive elements, such as LINE-1 and Alu Yb8, by bisulfate-PCR pyrosequencing.Here’s what they found:
- 75 mg/m2 was the best dose (that’s the FDA-approved dose).
- All doses resulted in less global DNA methylation.
- Surprisingly, patients who improved didn’t necessarily have less methylation.
The scientists say that 5-azacytidine is thought to make patients better by reducing methylation, but methylation didn’t correlate with health in their study. So, 5-azacytidine may have a second activity that improves patient health.
Despite positive clinical data, the group in Turkey says: Not so fast! They looked back at “real life” patients who were treated between 2005 and 2009 in a clinic (Hematological Oncology March 2011).
In this retrospective study, they found:
- Few patients had a complete response to the drug (12%)
- The death rate was high among 5-azacytidine treated patients who had progressed to a severe form of blood cancer (72%), as well as those with less severe blood cancers (59%).
What gives? The researchers explain that clinical trials are an artificial situation—only certain patients, such as those who are in a particular age range or those who don’t have additional illnesses, are chosen. But in the real world, patients don’t fit into neat classifications.
Which makes us wonder: Has the “sheen” worn off of 5-azacytidine?