The investigational drug axitinib produced tumor regression or stable disease in almost three-out-of-four patients with advanced thyroid cancer, a research team reported at the annual meeting of the American Society for Clinical Oncology in Chicago.
In this exploratory phase-2 trial, 18 out of 60 patients (30%) had their tumors shrink by 31 to 83 percent. Another 25 patients (42%) had stable disease, with no tumor progression or slight reduction in size, when measured at four months. Many of those patients still have stable disease.
"This is exciting," said study presenter Ezra Cohen, MD, PhD, assistant professor of medicine at the University of Chicago. "Until now we really didn't have anything to offer thyroid cancer patients with advanced disease that was refractory to standard measures."
Although this drug did not produce complete responses, it appears to have caused "significant tumor reduction in most subjects," he added, "Axitinib has prevented the disease from progressing in most patients, and in a lasting way."
In this trial, which began nearly three years ago, "the median duration of stable disease has not been reached," Cohen said. "Twenty-four patients are still in treatment."
Axitinib is a small molecule designed to prevent tumors from acquiring the blood supply they need to grow. It blocks all three known receptors for a substance called vascular endothelial growth factor (VEGF), a biologic factor tumors release in order to grow new blood vessels in the tumor, a process called angiogenesis.
The study confirmed that the drug worked as predicted. Treatment significantly reduced the presence of soluble VEGF receptors, VEGFR2 and VEGFR3, in blood. Levels of VEGF in the blood increased, suggesting that this growth factor was compensating for angiogenesis inhibition by axitinib.
More importantly, it prevented tumor growth. In only 10 out of 60 patients (17%) did the tumors continue to grow. Another 18 patients left the trial for other reasons, including toxicity. Five of them withdrew because of treatment-related adverse events.
The most common side effect was fatigue, affecting 50 percent of patients, but only 5 percent had severe fatigue and only one patient left the trial for this reason. Axitinib also caused hypertension in about 28 percent of patients and a range of digestive disorders, including, diarrhea (47%), nausea (32%), consequent weight loss (23%) and vomiting (13%). Several patients complained of headaches or rash.
This study enrolled patients with several different types of thyroid cancer and it "had an effect of all sub-types," Cohen said.
All patients in this trial had advanced thyroid cancer. Many had already been given standard therapy-such as surgery or treatment with radioactive iodine. Others, because of their advanced disease, were not candidates for standard treatments.
"It's a relief to have a real option for these patients," Cohen said. "The standard chemotherapy for refractory thyroid cancer is not very effective and can have multiple significant side effects. It appears, in this early study, to keep the cancer from growing for a significant period for the majority of patients without doing any real damage to their quality of life."
The American Cancer Society predicts there will be 33,500 new thyroid cancer cases in the United States in 2007 and 1,530 deaths.
A follow-up trial testing axitinib in patients who have not responded to standard chemotherapy is ongoing.Pfizer, the maker of axitinib, funded this trial. Additional authors of the study include Everett Vokes of the University of Chicago; Lee Rosen of Premiere Oncology in Santa Monica, Calif.; Arlene Forastiere of Johns Hopkins University; Merrill Kies of MD Anderson Cancer Center; Francis Worden of the University of Michigan; Madeleine Kane of the University of Colorado, Roger Cohen of Fox Chase Cancer Center; and Katherine Liau and David Shalinsky of Pfizer.