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Two-drug combo shows benefit in lung cancer


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http://www.mdanderson.org/news-and-publ ... ancer.html

When combined with the standard chemotherapy drug Taxotere® (docetaxel), the oral targeted therapy Zactima® (vandetanib) improves progression-free survival for patients with advanced non-small cell lung cancer.

Researchers from M. D. Anderson presented the findings of the first-of-its-kind, international Phase III trial at the American Society of Clinical Oncology's (ASCO) annual meeting in May.

Significance of research: Vandetanib, an oral tyrosine kinase inhibitor, is the first agent to target two lung cancer receptors - Epidermal growth factor receptor (EGFR) and Vascular endothelial growth factor receptor (VEGFR).

"In lung cancer, EGFR targets the tumor cell, and VEGFR targets the blood vessels,” says the study’s international principal investigator, Roy Herbst, M.D., Ph.D., chief of the section of Thoracic Medical Oncology in M. D. Anderson's Department of Thoracic/Head and Neck Medical Oncology. “With vandetanib, we're really targeting the entire tumor environment at the same time.

"As a dual inhibitor, vandetanib may provide cost savings to patients because they potentially can be treated with one therapy instead of two," he says.

According to the American Cancer Society, lung cancer accounts for the most cancer-related deaths in the United States. In 2009, more than 219,000 will be diagnosed with lung cancer, and more than 159,000 are expected to die because of it.

Research methods: The study enrolled 1,391 patients who:

Had non-small cell lung cancer

Were treated at 198 centers across the country

Were treated between May 2006 and April 2008

Had previously received chemotherapy

Participants received either:

Docetaxel and a placebo (inactive substance)

Docetaxel and vandetanib

Median follow-up was 12.8 months.

The study's goal was to examine progression-free survival.

Primary results: Patients who received docetaxel and vandetanib had a 21% higher rate of reduction in disease progression than those who received docetaxel alone.

Median progression-free survival was:

17.3 weeks for those who received both drugs

14 weeks for those who received only docetaxel

While it trended positive, there was no statistical difference in overall survival between the two groups.

Additional resultsL: Although agents that target VEGFR are associated with increased toxicity and side effects that include pulmonary bleeding, patients who received vandetanib experienced fewer significant side effects than those who received docetaxel alone.

People who took vandetanib and docetaxel had minor side effects. These included diarrhea, skin rash, and neutropenia (low level of a type of white blood cells).

Those who took docetaxel alone had more serious side effects. These included: nausea and anemia

What’s next?: "This study will have immediate clinical implications,” Herbst says. “We need to build on this research and turn our focus toward better identifying molecular markers, with the ultimate goal of personalizing care.

"Our ultimate goal always is to improve survival for our patients; however, the improved time to progression with fewer significant effects is important. Hopefully this study will serve as the foundation for the merger of personalization and discovery with now-proven safety and efficacy."

Herbst plans to update the survival data later this year.

Vandetanib also is being studied as a single agent in lung cancer and thyroid cancer.

This article was adapted by Dawn Dorsey from an M. D. Anderson news release.

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