Lung cancer patients - Blocking blood vessels provides new option for many

Main Category: Lung Cancer
Article Date: 14 May 2005 - 10:00 PDT

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Patients with a particular type of advanced lung cancer may have a new option based on data presented here at the 2005 annual meeting of the American Society of Clinical Oncology showing that combining a drug that cuts off the cancer's blood supply with standard chemotherapy can shrink tumors and extend life.

In fact, adding the "anti-angiogenesis inhibitor" bevacizumab (Avastin) to standard chemotherapy extended median survival beyond one year for the first time among patients with advanced non-small cell, non-squamous lung cancer, reported Alan Sandler, M.D., principal investigator of the multi-center study and director of Thoracic Oncology at the Vanderbilt-Ingram Cancer Center.

As a result of the study conducted through the Eastern Cooperative Oncology Group, ECOG recommends the regimen of bevacizumab plus the chemotherapies paclitaxel and carboplatin (PCB) as the new standard treatment for patients with this stage and type of lung cancer.

"These results show, for the first time, an improvement in survival with the addition of a targeted agent to standard chemotherapy in this patient population, and first time median survival has been extended beyond one year in advanced, non-small cell lung cancer," Sandler said.

The study enrolled 878 patients with advanced, non-squamous, non-small cell lung cancer between July 2001 and April 2004. Of those, 444 were randomly assigned to receive paclitaxel and carboplatin, considered the standard therapy, and 434 were assigned to receive the chemo combination plus bevacizumab.

Median survival - the point at which half the patients enrolled in the study had died - was 12.5 months for patients who received bevacizumab plus chemotherapy compared to 10.2 months for patients who received standard chemotherapy alone.

"We also observed improvements in patient benefit with the bevacizumab arm, including the time between enrollment and when tumors began growing again and the proportion of patients whose tumors shrunk in response to therapy," said Sandler, who is also professor of Medicine in Oncology at Vanderbilt University School of Medicine.

The overall tumor response rate for the patients who received bevacizumab plus chemotherapy was 27 percent, compared to 10 percent for patients who received chemotherapy alone. Progression-free survival was 6.4 months for the bevacizumab-plus-chemotherapy arm, compared to 4.5 months for chemotherapy alone.

Bevacizumab, which was approved last year for treatment of advanced colorectal cancer, binds to and interrupts the activity of the vascular endothelial growth factor (VEGF). VEGF's signals prompt the recruitment and growth of new blood vessels to provide tumors with the oxygen and nutrients they need to grow and spread. Interrupting that process destroys these vessels.

However, earlier studies with this drug among lung cancer patients found a serious risk of life-threatening bleeding, particularly among those with a type of cancer called squamous cell carcinoma. By excluding squamous cell cancers from the study, the risk of life-threatening bleeding was "substantially decreased," Sandler said.

The American Cancer Society estimates that more than 172,000 new cases of lung cancer will be diagnosed this year, and the disease will claim more than 163,000 lives. Of those, about 85 percent will be non-small cell cancers, and of that group, about 85 percent will fall in the non-squamous category. Patients with brain metastases were also excluded from the study, which account for about 10 percent of patients. "Even though this drug appears to benefit a subset of lung cancer patients, it is still a sizeable group of patients," Sandler said. The U.S. Food and Drug Administration has not yet considered bevacizumab for this potential new indication.

In addition to Sandler and colleagues at Vanderbilt-Ingram, the study presented at ASCO included co-authors from Dana Farber Cancer Center, Johns Hopkins University, Case Western University, the University of Wisconsin and the University of Missouri-Ellis Fischel Cancer Center.

Affiliated with Vanderbilt University and Medical Center in Nashville, the Vanderbilt-Ingram Cancer Center is the only National Cancer Institute-designated Comprehensive Cancer Center in Tennessee and one of only 39 to earn this highest distinction nationwide. Vanderbilt-Ingram includes a robust multi-disciplinary basic, translational, clinical, and population-based cancer research enterprise as well as state-of-the-art cancer care and clinical trials for adults and children with cancers, and a commitment to the community through cancer education, outreach and information. To learn more: http://www.vicc.org.

Contact: Cynthia Floyd Manley
cynthia.manley@vanderbilt.edu
615-430-8320
Vanderbilt University Medical Center
http://www.mc.vanderbilt.edu/reporter

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