Drug Combination Beats Previously Resistant Cervical Cancer
June 5, 2006 – With commonly available treatment strategies, 90 percent of women with recurrent cervical cancer die within five years. So physicians are understandably eager to uncover more effective drug therapies, and Siteman Cancer Center researchers at Washington University School of Medicine in St. Louis have now obtained encouraging results by combining a traditional cell-killing agent with Avastin, a recently developed inhibitor of blood-vessel growth.
Patients involved in testing the new combination therapy suffered from advanced cervical cancer that had spread to multiple sites in the body. Several prior rounds of standard chemotherapeutic agents had failed to stop their cancer's growth. But four of the six patients in this preliminary study responded to the therapy – in one case, a patient's tumors disappeared completely while she was on the drug combination.
"Hers was a remarkable, dramatic response," says first author Jason D. Wright, MD, instructor of obstetrics and gynecology and a researcher with the Siteman Cancer Center. "Another patient had a partial response – her tumors decreased in size – and two patients had stable disease – their tumors did not continue to grow. These results definitely indicate that further trials of the drug combination are warranted."
The study will appear in an upcoming issue of the journal Gynecologic Oncology and is now available online.
Avastin (chemical name bevacizumab), a monoclonal antibody, inhibits the formation of new blood vessels by binding to a blood-vessel growth factor. Prior research has shown that the density of blood vessels within cervical tumors increases as cervical cancer advances, so by binding to the blood-vessel growth factor, Avastin targets a mechanism that plays a prominent role in cervical cancer development and progression.
Avastin has been used with success in clinical trials for colon, renal and ovarian cancer, but has never before been studied as a treatment for cervical cancer. Trials of Avastin as a treatment for ovarian and endometrial cancer are also underway at the School of Medicine.
"When Avastin became available about five years ago, it was initially used alone to treat cancer," Wright says. "More recently, research has shown that it can be more effective when it's combined with a chemotherapeutic drug."
Exactly how Avastin affects tumors is not yet certain. In addition to interfering with the growth of new blood vessels, some evidence suggests Avastin restores normal structure to the poorly functioning blood vessels within tumors. Doing so may promote the delivery of chemotherapeutic drugs to the tumor interior. Scientists also propose the drug blocks repair of blood vessels that become damaged by chemotherapy, starving the tumor of its nutrient supply.
Wright's study paired Avastin with 5-fluorouracil, a long-established anticancer drug. The patients suffered relatively few side effects from the therapy. These included anemia, mild high-blood pressure and protein in the urine, an indicator of kidney problems.
The researchers have subsequently treated additional patients with the combination therapy and have seen impressive response rates, according to Wright.
"At this early stage, we don't yet know how long to give Avastin to cervical cancer patients or whether it will be more effective for them alone or in combination with chemotherapy," Wright says. "Our initial results are helping us to further develop clinical trials."
Wright JD, Viviano D, Powell MA, Gibb RK, Mutch DF, Grigsby PW, Rader JS. Bevacizumab combination therapy in heavily pretreated, recurrent cervical cancer. Gynecologic Oncology, now available online.