June 2, 2011 Scientists have identified a drug combination, when used in advanced lung cancer patients, shows a survival advantage in patients who no longer respond to existing therapies. They found that bexarotene and erlotinib can each repress the critical cell cycle regulator: cyclin D1. The drug combination also broadened the reach to include a specific subset of patients, such as those resistant due to the presence of a ras mutation in their cancer.
The study was published in the June issue of Cancer Prevention Research.
"Erlotinib has been found to be most effective in women of Asian descent who are never smokers with bronchioalveolar carcinoma, and who tend to have activating mutations of the epidermal growth factor receptor," said Ethan Dmitrovsky, M.D., an Associate Scientific Director of the Samuel Waxman Cancer Research Foundation and a senior author on the study. "None of the patients in our study fit that demographic profile."
In fact, the patients in the cohort who exhibited the greatest response included non-Asian men who were smokers. Advanced lung cancer patients with refractory disease have a survival of four months or less with traditional chemotherapy. The results of the study showed a median survival of five and a half months and longer. Three patients from the trial are now living two to four years beyond the expected average.
The study's results were recently duplicated by a group of MD Anderson scientists, noted Konstantin Dragnev, M.D., who led this trial and is an associate professor at Dartmouth Medical School, in Hanover, N.H.
The most exciting part of the research, which was funded in part by the Samuel Waxman Cancer Research Foundation, "is that scientists were able to make a dent in the ras mutation subset of patients," said Dmitrovsky, who is a professor at Dartmouth Medical School. "This area is an unmet medical need. These are often times the most difficult lung cancers to treat."
"This study gives hope to a large group of lung cancer patients who currently have very few options," said Linda Wenger, the Executive Director of Uniting Against Lung Cancer. "It's critical for nonprofit foundations to continue supporting research in underserved areas to bring new ideas to the clinic."
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- Konstantin H. Dragnev, Tian Ma, Jobin Cyrus, Fabrizio Galimberti, Vincent Memoli, Alexander M. Busch, Gregory J. Tsongalis, Marc Seltzer, David Johnstone, Cherie P. Erkmen, William Nugent, James R. Rigas, Xi Liu, Sarah J. Freemantle, Jonathan M. Kurie, Samuel Waxman, and Ethan Dmitrovsky. Bexarotene Plus Erlotinib Suppress Lung Carcinogenesis Independent of KRAS Mutations in Two Clinical Trials and Transgenic Models. Cancer Prevention Research, 2011; 4: 818-828 DOI: 10.1158/1940-6207.CAPR-10-0376
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