“Recurrent endometrial cancer is very difficult to treat,” said Brian M. Slomovitz, M.D., professor of clinical obstetrics and gynecology, Director of Gynecologic Oncology and lead author of the article, who conducted the research with colleagues at MD Anderson Cancer Center in Houston before joining the Miller School of Medicine’s Sylvester Comprehensive Cancer Center last August. “It’s rare to get a good response to conventional chemotherapy after the first round. We needed to look for other options that would provide the best possible response right from the start.”
The researchers began by selecting an mTOR (mammalian target of rapamycin, a molecular pathway whose signaling has been shown to be associated with aggressive disease and poor prognosis) inhibitor called everolimus. Prior research had shown few positive responses, but a relatively high stable disease rate, said Slomovitz.
They needed a second drug that, in combination, would help produce a better effect. Preclincal work has demonstrated that hormonal inhibition work synergistically with the mTOR inhibitor. The choice was a hormonal product called letrozole, which is an approved drug for breast cancer patients.
“The two drugs had a favorable toxicity profile, meaning they can go together without harming the patients,” said Slomovitz. “Each would help the other work better and make the tumors more responsive. The nice thing about this treatment was that it wasn’t a combination of conventional chemotherapies that would poison all cells. We wanted a targeted therapy, and we believed that the combination would improve the outcome of either drug alone.”
The clinical trial results proved them right. Thirty-eight patients at two sites, with a median age of 62, were enrolled. The combination treatment achieved a 50 percent stable disease rate (the cancer stopped progressing) and a 32 percent clinical response rate (complete or partial regression).
The next step – a larger national study to determine if the combination therapy can outperform hormonal therapy alone – has already begun, with Slomovitz as its chair. The researchers plan to enroll 84 women at 30 centers, with Sylvester as the lead and the only center in Florida participating in the study. Results are expected in about 18 months.
Miller School Departments, Centers and Institutes