Mayo Clinic today reported promising interim results from a Phase II trial of a new combination therapy for patients with recurrent ovarian cancer that is resistant to platinum therapy. Thirty-three percent of study participants achieved either complete or partial tumor regression from the therapy, which combines flavopiridol and cisplatin.

Findings from this Phase 2 Consortium (P2C) clinical trial were presented by the study’s primary investigator, Keith Bible, M.D., Ph.D., at the Molecular Targets and Cancer Therapeutics International Conference, a jointly-sponsored symposium of the American Association for Cancer Research, National Cancer Institute and the European Organization for Research and Treatment of Cancer.

“We are encouraged by the interim results of this trial,” says Dr. Bible, a medical oncologist and researcher at Mayo Clinic. “Platinum-resistant ovarian cancer responds poorly to traditional therapies, and we’ve been working toward developing more effective treatments for this disease. This combination looks very promising.”

More than 22,400 women in the United States will be diagnosed with ovarian cancer this year, according to the American Cancer Society, and nearly 15,300 women will die from it. Women with late-stage ovarian cancer have very few options, and most standard treatments include platinum-based therapies (cell-damaging agents).

In this study, the researchers evaluated a combination therapy using flavopiridol (an investigational anti-cancer agent that also boosts the effects of other therapeutics including cisplatin) with cisplatin (a platinum compound) for women with platinum-resistant ovarian or primary peritoneal (lining of the abdominal cavity) cancers. The researchers found in earlier preclinical studies that flavopiridol significantly boosts the anti-cancer effects of cisplatin, and later conducted a Phase I clinical trial to pilot the combination in patients (KC Bible et al, Clinical Cancer Research, 11:5935, 2005). The present Phase II trial was designed to extend this work and better determine this therapy’s effectiveness against platinum-resistant cancers.

Dr. Bible and his co-investigators treated 18 platinum-resistant Caucasian patients with this combination therapy. Of the 18 patients, all of whom were receiving the therapy as a second-line treatment after disease progression, one patient experienced complete response (all signs of cancer gone) and five other patients experienced partial responses (tumor regression). The 33 percent overall response rate (6 of 18 patients) is about twice as high as seen using traditional chemotherapy regimens.

The researchers also offered the combination therapy to five patients with platinum-sensitive (original therapy resulted in no recurrence for greater than 12 months) ovarian cancer. Of these women, one experienced complete response and three others partial response.

“We now need to expand this trial to validate these interim results in additional patients,” says Dr. Bible. “We’re also looking for ways to further boost the anti-cancer effects of the combination, in hopes of developing even more effective approaches to ovarian cancer.”

Other members of the P2C research team included Prema Peethambaram, M.D.; Jill Burton; Ann Oberg, Ph.D.; Leigh Gomez-Dahl; Crescent Isham; Jennifer Tibodeau, Ph.D.; Tamra Chomjak; Scott Kaufmann, M.D., Ph.D.; and Charles Erlichman, M.D.; all of Mayo Clinic. Additional collaborators included A. Dimitrios Colevas, M.D., Stanford University Medical School, Palo Alto, Calif.; and John Wright, M.D., Ph.D., National Cancer Institute, Bethesda, Md.

The Phase 2 Consortium (P2C) is a multi-center consortium specializing in Phase II clinical trials of anti-cancer agents. The consortium is coordinated by Mayo Clinic Cancer Center (which has sites in Phoenix/Scottsdale, Ariz., Jacksonville, Fla., and Rochester, Minn.). Other P2C members include Cancer Therapeutics Research Group, Singapore; The Center for Cancer Care and Research, St. Louis; Howard University Cancer Center, Washington, D.C.; Karmanos Cancer Institute, Detroit; Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minn.; Sidney Kimmel Comprehensive Cancer Center, Baltimore; Siteman Cancer Center, St. Louis; UCSF Comprehensive Cancer Center, San Francisco; and University of Wisconsin Comprehensive Cancer Center, Madison, Wis.

The National Institutes of Health provided the majority of funding for this research.

For more information on breast cancer research at Mayo Clinic Cancer Center, visit the Women’s Cancer Program Web site.

Source: Mayo Clinic