New Treatment May Boost Survival in Advanced Lung Cancer Cases

Patients on 'epigenetic' combo lived an average of two months longer than expected in small, early study

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Lung Cancer

WEDNESDAY, Nov. 9 (HealthDay News) -- For the first time, "epigenetic" therapy has shown promise in patients with solid tumors, in this case non-small cell lung cancers.

Of 45 patients in a trial of this experimental treatment, two had a complete response to therapy, one had a partial response and one is still alive more than four years after starting therapy.

"It's not a home run, but this trial has opened the door for further research into epigenetic therapy," said Dr. Stephen Baylin, co-author of the study appearing online Nov. 9 and in the December issue of Cancer Discovery.

Other experts were both hopeful and cautious.

"The exciting part of this study is that they're using therapies that have really never worked in solid tumors, and this is one of the first studies to show that these types of therapies may work in solid tumors, and more specifically in lung cancer," said Dr. Benjamin Levy, director of thoracic medical oncology at Beth Israel Medical Center in New York City. "But until we get this validated in larger studies, it's unclear where this type of therapy in terms of altering epigenetic regulation is going to have a place in lung cancer."

"You have to view this as extremely preliminary. It is a small study with what one could almost argue are anecdotal-type findings," said Dr. Edward Kim, chief of head and neck medical oncology at MD Anderson Cancer Center in Houston. "There's not a lot I could apply to my patients, though the results are intriguing."

Some 80 percent of lung cancers are non-small cell lung cancers, which have few effective treatments and, consequently, a dire prognosis.

Epigenetic therapy involves targeting the proteins wrapped around DNA, which regulate changes in actual gene expression. Unlike genetic mutations, epigenetic abnormalities can be reversed, explained Levy.

This phase 1/2 trial involved 45 patients with metastatic non-small cell lung cancer who had tried and failed multiple other therapies.

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.

SOURCES: Stephen B. Baylin, M.D., professor, oncology, and deputy director, Kimmel Cancer Center, Johns Hopkins University, Baltimore; Edward Kim, M.D., chief, section of head and neck medical oncology, MD Anderson Cancer Center, Houston; Benjamin Levy, M.D., director, thoracic medical oncology, Beth Israel Medical Center, New York City; Nov. 9, 2011, Cancer Discovery, online

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