Drug is first to control recurrent low-grade ovarian cancer

A phase 2 clinical trial of a targeted therapy provides evidence that there might, at last, be a treatment that shrinks or stifles the growth of recurrent low-grade serous ovarian cancer.

Women who have low-grade disease tend to be younger and survive longer than those with high-grade ovarian cancer, but when their cancer persists or comes back, it almost always thwarts treatment. Between 2% and 4% of patients respond to chemotherapy. Hormonal therapies do modestly better, with a 9% response rate.

In the clinical trial of the drug selumetinib published in the February edition of The Lancet Oncology, eight of 52 (15 percent) patients had a complete or objective partial response (tumor shrinkage) and 34 (65 percent) had no disease progression during the two-year course of the study.

"These are remarkably encouraging results for what can ultimately be a devastating disease," says David Gershenson, M.D., professor in MD Anderson's Department of Gynecologic Oncology and Reproductive medicine, the paper's senior author.

Selumetinib hasn't made Doris Elliott's recurrent low-grade ovarian cancer disappear. But it shrank all of her tumors and has arrested their development for five years running.

For Dotsy Elliott, cancer under control for five years and counting After her diagnosis in 1997, six rounds of chemotherapy kept cancer at bay until 2005. Surgery and nine rounds of chemotherapy did little to slow progression. Another clinical trial helped for about 18 months. Out of treatment options in 2007, her MD Anderson oncologist, Rob Coleman, M.D., told her about a phase II clinical trial of the MEK1/2 inhibitor selumetinib. The drug aims to block two common mutations in low-grade ovarian cancer, KRAS and BRAF.

"They gave me literature, suggested I call my family, talk about it and think about it. I said 'there's nothing to think about, I'm doing it.' That was five years ago, and I'm still here. I'm not complaining," says Elliott, who is known to all as Dotsy, a childhood nickname bestowed by her sister.

Elliott has lived in Shiner, Texas, all of her life. She works in hospitality at Spoetzl Brewery, maker of Shiner Beers. "I've worked at the brewery for 17 years. It's been fun." The souvenir shop where she works is popular with visitors because they can get a free beer (or lemonade) there.

"I work full time and I still do everything I've always done," she says. Elliott remains on the clinical trial, making monthly visits down U.S. Highway 90 to MD Anderson.

Side effects "What's so unusual about her is that she's run the gamut of therapy before coming onto this novel molecularly targeted approach and has responded really remarkably for a refractory situation like hers," Coleman says.

There were side effects, Elliott notes. As a veteran of multiple chemotherapy regimens, she recognizes those come with the territory. The worst was blistering and a rash on her face and neck.

"It was really, really bad at first. My face was one big sore. It lasted several months," she says. "I got some strange looks, but I didn't care, I'm still here." A few blisters endure, but she covers them with makeup.

Clinical trials can be nerve-wracking for some, because it's hard to know what to expect, she says. "It's like anything, Advil works for me, but doesn't for my brother. It's too bad this drug doesn't work for everybody. But it's sure worth the try."

Gershenson will lead a larger phase 2-3 international clinical trial with investigators from the National Cancer Institute's Gynecological Oncology Group (GOG) and the United Kingdom. The study will enroll 250 patients and is likely to begin later this summer.

In an accompanying commentary in Lancet Oncology, two German oncologists who did not participate in the research, note that the study is a step toward individualized treatment for ovarian cancer that reflects important molecular differences between low-grade and high-grade disease.

Additional information MD Anderson news release