NEW ORLEANS, LA -- May 26, 2000 -- A Phase-II trial has determined that anti-angiogenesis treatment restricting the vascular epithelial growth factor (VEGF) delays time to relapse in patients with metastatic lung cancer, when used in conjunction with a standard chemotherapy regimen.
VEGF is a natural growth factor in the body. It is also released by tumor cells to stimulate blood-vessel formation within and around the tumor. The anti-VEGF monoclonal antibody targets VEGF to prevent angiogenesis at the tumor site.
The trial, described in New Orleans, LA, at the 36th annual meeting of the American Society of Clinical Oncology, was conducted at Vanderbilt University. Researchers used anti-VEGF in combination with two chemotherapy drugs, carboplatin and paclitaxel.
The 99 patients enrolled were randomized to receive chemotherapy only, or to receive chemotherapy followed by the recombinant human monoclonal anti-VEGF antibody. They were further stratified to received the chemotherapy with anti-VEGF at low or at high doses. Mean age of these patients was 62 years.
Response rate for the 35 patients taking high-dose anti-VEGF and chemotherapy was 40 percent; response rates among the 32 patients taking the lower dose of anti-VEGF and chemotherapy was 21.9 percent; and for the 32 taking chemotherapy alone, 31.3 percent.
Metastatic lung cancer took almost twice as long to recur in patients taking the maximum therapy. Time to relapse was 7.4 months for the patients taking high-dose anti-VEGF and chemotherapy; 4.3 months for those taking the lower dose of anti-VEGF and chemotherapy; and 4.2 months for those taking chemotherapy alone.
"These are pretty profound differences," said Russell DeVore, MD, principal author of the Vanderbilt study. He said the data suggest that anti-angiogenesis therapy may improve outcomes compared with chemotherapy alone.
Side effects of the treatment were severe, however. Six patients who received anti-VEGF experienced hemoptysis, or sudden bleeding from their lung tumors, which caused death in four of the six.
Dr. DeVore said all four patients who died had squamous-cell histology. Squamous-cell carcinoma of the lung tends to occur in the larger airways, and so future anti-VEGF studies might not enroll patients with this disease, he said.