UACC physician-scientists’ study findings reported at international gyn meeting

Findings from a randomized study involving patients with newly diagnosed advanced-stage ovarian cancer, overseen in part by UACC physician scientists, were presented at the international meeting of the European Society of Gynecological Oncology in Liverpool, England, Oct. 19.

Bradley Monk, MD, of the University of Arizona Caner Center at St. Joseph’s in Phoenix, was a co-investigator for quality of life. The study was developed through the Ovarian Committee of the Gynecologic Oncology Group (GOG), chaired by Michael A. Bookman, MD, UACC-Tucson, who also served as the local study chair.

The study compared outcomes from standard (three-weekly) chemotherapy using carboplatin and paclitaxel versus a “dose-dense” combination of weekly paclitaxel with standard three-weekly carboplatin, following encouraging data from a randomized trial conducted by the Japanese Gynecologic Oncology Group.

In the GOG trial, patients were also allowed to receive bevacizumab, a monoclonal antibody that binds to vascular endothelial growth factor (VEGF), which is commonly over-produced by ovarian cancer, leading to tumor blood vessel formation, or angiogenesis.

A total of 692 patients participated in the trial, with 580 (84 percent) opting to receive bevacizumab with their chemotherapy, while 112 (16 percent) opted to receive chemotherapy without bevacizumab.

Overall, the study demonstrated no difference in the risk of disease progression between the two arms (standard versus weekly therapy). In addition, among patients who elected to receive bevacizumab, there was also no difference in the risk of progression between the two arms. 

However, in a provocative finding, the 112 patients who received chemotherapy without bevacizumab demonstrated a four-month improvement in the time to progression, favoring weekly treatment, compared to the standard treatment regimen.

Carboplatin is the most important drug used in the treatment of ovarian cancer, and is routinely administered once every three weeks. Prior studies have not demonstrated an advantage to weekly dosing, which achieves lower peak drug levels, and may actually limit tumor drug penetration, Dr. Bookman said.

In contrast, earlier studies with weekly paclitaxel (as a single agent) demonstrated improved outcomes in patients with recurrent breast and ovarian cancer, without increasing the risk of non-hematologic toxicity. While this may be related to tumor growth kinetics, it has also been postulated that weekly exposure to paclitaxel can have an anti-angiogenic effect, similar to the activity of bevacizumab.

In addition, while hair loss is universal when paclitaxel is administered once every three weeks, hair loss is less frequent and less severe when using a weekly schedule, further suggesting that switching to a weekly schedule could improve outcomes while minimizing non-hematologic toxicity.

These new findings from GOG will contribute to the ongoing debate regarding optimal therapy for women with newly diagnosed ovarian cancer.  Indeed, these data provide confirmation that weekly dosing with paclitaxel might be the preferred strategy, confirming and extending data from the Japanese GOG. In addition, the anti-angiogenic effect of weekly paclitaxel dosing may obviate the need to incorporate bevacizumab during initial treatment, minimizing overall treatment costs while improving long-term outcomes, Dr. Bookman said.

In an interesting translational objective, the GOG study is also evaluating the ability of perfusion computed tomographic (CT) imaging to serve as an early predictive biomarker of patient outcomes, as approximately 15 percent of patients will have tumors that are resistant to primary chemotherapy. 

Preliminary imaging data suggest that weekly paclitaxel can reduce tumor blood flow during the very first cycle of chemotherapy, while this effect is less prominent with standard three-week dosing. These studies were conducted in collaboration with the American College of Radiology Imaging Network, and patients from the University of Arizona participated in both components of the GOG trial.

Additional UACC collaborators on the study were Drs. Diego Martin and Bobby Kalb of the Department of Medical Imaging.

- Oct. 22, 2013