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Mixed News on Tough-to-Treat Lung Cancer
Date:1/10/2012

By Jenifer Goodwin
HealthDay Reporter

TUESDAY, Jan. 10 (HealthDay News) -- Dutch researchers report disappointing results from an early clinical trial of the drug Nexavar (sorafenib) in fighting a tough-to-treat form of lung cancer.

But, in better news, an experimental drug known as ganetespib showed promise in laboratory and animal experiments.

The results of both studies were to be presented Tuesday at an American Association for Cancer Research/International Association for the Study of Lung Cancer meeting in San Diego.

In recent years, researchers have made some headway in finding treatments to combat lung cancer, which often doesn't respond well to chemotherapy, explained Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society.

Those treatments include drugs such as crizotinib (Xalkori) and erlotinib (Tarceva), which are most effective in tumors that contain certain genetic mutations.

However, those drugs tend to not work well in people with tumors that contain a particular type of mutation in the KRAS gene. KRAS is the most common molecular mutation, present in about 25 percent of people with non-small cell lung cancers such as adenocarcinoma, particularly smokers, said Dr. Paul Bunn, a professor of lung cancer research at the University of Colorado and executive director of the International Association for the Study of Lung Cancer.

"The patients who have this mutation have a somewhat worse prognosis than patients who don't have this mutation, and have worse outcomes with chemotherapy," Bunn said. "Most drugs produce a shrinkage of the tumor in less than 10 percent of KRAS patients."

While a smaller, even earlier trial showed sorafenib might be that drug, the latest findings were not impressive. This larger trial by researchers in the Netherlands involving 57 patients with non-small cell lung cancer who had already failed chemotherapy and who had the KRAS mutation showed the median progression-free survival was just 2.3 months. Overall survival was about five months.

"They were undoubtedly hoping that progression-free survival would be longer, maybe four or five months, and overall survival would be six or eight months," Bunn said. "The results were not encouraging. Their basic conclusion is that we should find something better for these patients, and not spend a lot of time on a big randomized trial to show it has a teeny effect or no effect."

In addition, sorafenib was not compared to other drugs, or even to no treatment, Lichtenfeld said, so there is no way of gauging if the 2.3 months represents a true benefit above and beyond what patients would experience otherwise.

A second study done on non-small cell cancer cells and mice with the KRAS mutation showed more promise, experts said.

In it, researchers tested the drug ganetespib, which inhibits the Hsp90 protein. When combined with other cancer drugs, ganetespib seems to affect multiple other proteins present in the cancer cell that help the cancer cell thrive, Lichtenfeld said.

"The presence of this protein [Hsp90] really directs or impacts many proteins within the cancer cell that are necessary for it to survive," Lichtenfeld said. "If you can block that protein's effect, you then have other proteins that are blocked, and by blocking them you could shut down the cancer cell and severely impact the cell and its growth patterns. That is interesting and exciting from a laboratory point of view."

However, Lichtenfeld noted, "the problem we always face is translating what we see in the laboratory to clinical medicine. There are so many times we have promising and exciting findings in the laboratory that don't translate into patients, but occasionally they do."

The next step will be larger trials involving cancer patients, Bunn said.

"I would say this other approach is more promising than the sorafenib, and certainly worthy of additional studies, but not ready for clinical primetime," Bunn said.

Non-small cell lung cancer is the most common type of lung cancer. Non-small cell cancers include squamous cell and adenocarcinomas.

"The big picture is we are learning about these mutations that tell us something about lung cancer, which has in some cases given us targets to guide us to use certain drugs because we know they have a higher chance of being effective," Lichtenfeld said.

Lung cancer is the leading cause of cancer deaths in the United States for men and women, killing an estimated 157,000 people this year, according to the American Cancer Society.

Experts note that research presented at meetings has not been subjected to the same type of rigorous scrutiny given to research published in peer-reviewed medical journals.

More information

The U.S. National Cancer Institute has more on lung cancer.

SOURCES: Len Lichtenfeld, M.D., deputy chief medical officer, American Cancer Society, Atlanta; Paul Bunn, professor, lung cancer research, University of Colorado, and executive director, International Association for the Study of Lung Cancer; Jan. 9, 2012, presentations, American Association for Cancer Research/International Association for the Study of Lung Cancer meeting, San Diego


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