Related story: A magnificent seven
David Gershenson, M.D., has long puzzled over a rare, wily adversary: the slow-growing but extremely chemo-resistant low-grade serous ovarian cancer. Once it recurs, which it usually does, there are few effective treatments. The professor in MD Anderson’s Department of Gynecological Oncology and Reproductive Medicine and his research team gambled they could target mutations in the MAPK pathway to combat tumor growth.
Disease: Low-grade serous carcinoma of the ovary (LGSC) is less common and aggressive than high-grade types of ovarian cancer, but it resists many kinds of chemotherapy. Relapse after treatment is common.
Oral medication: Selumetinib is given at 50 mg twice daily until disease progression.
Clinical trial: In this open-label, single-arm Phase II study, women with recurrent low-grade serous ovarian, or peritoneal carcinoma, are given selumetinib until progression.
Patients: Participants in the study must be 18 years of age or older, have pathologically confirmed recurrent disease and have been off chemotherapy for at least four weeks.
Results: Of 52 women enrolled in the study, eight had an objective response to treatment. One had a complete response, and seven had partial responses. Thirty-four (65%) had stable disease.
“These are remarkably encouraging results for what can ultimately be a devastating disease,” Gershenson says.
The patient: Catching a break
When a clinical trial failed to stop progression of Dotsy Elliott’s relapsed ovarian cancer in 2007, she didn’t want to take a break from treatment.
But her oncologist, Robert Coleman, M.D., professor in MD Anderson’s Department of Gynecologic Oncology and Reproductive Medicine, suggested she stop treatment temporarily. He had something in mind, he told her, but wanted her to rest for a few weeks first.
Despite two surgeries and more than a dozen cycles of chemotherapy before the initial clinical trial, the tumors had continued to grow.
Coleman thought Elliott might benefit from a new clinical trial testing the MEK 1/2 inhibitor selumetinib. The drug aims to block two common mutations in low-grade ovarian cancer, KRAS and BRAF. To enroll in the trial, Elliott needed to have been off treatment for four weeks. Thus the break.
When told about the trial, Elliott was relieved. “I said, ‘Where do I sign?’” she recalls with a laugh.
She’s done well for the five years she’s been on selumetinib. Her tumors have shrunk, and she’s been healthy enough to keep working full-time through treatment at the Spoetzl Brewery in Shiner, Texas.
Side effects have included an intermittent rash on her face, mouth sores and bleaching of her hair to “the yellowest blonde you’ve seen in your life.”
Along the way, she, Coleman and her medical team have become close. “We’re all old friends now,” she says. “They know more about me than I do.”