One of the drugs used in the study, azacitidine, had been tested on different cancers decades ago but was deemed too toxic to use. It's now approved in much lower doses for patients with myelodysplastic syndrome, which can be a precursor to leukemia.
These researchers also used low doses of azacitidine, combined with a newer drug, etinostat. Each drug targets a different epigenetic pathway.
With this combination, patients lived an average of 6.4 months, which is about two months longer than what otherwise would have been expected, said Levy.
Two patients saw "a virtually complete response," said Baylin, who is a professor of oncology and deputy director of the Kimmel Cancer Center at Johns Hopkins University in Baltimore. One lived for three years after therapy before dying of a different type of lung tumor. The other is still alive three years after joining the trial and "his original disease metastasis to his liver has not come back."
After completing the epigenetic therapy, four patients went on to respond to other therapies. "This has set up the possibility that we're priming patients so that subsequent therapies work better," Baylin said, cautioning that this is not yet proven.
Importantly, side effects were "milder than typical chemotherapy," Baylin said. "No patient had to come off of the trial because of toxicity."
The researchers were also able to identify biomarkers that may be able to predict which patients will respond well to this epigenetic therapy.
"This doesn't work in a majority of patients, but there is a small subset that really derive exceptional benefits from this approach," said Rudin. The challenge now is to identify these patients, he added.
Although the study suggested an association between the therapy and increased survival, it does not prove a cause-and-effect.
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