Featured Research

from universities, journals, and other organizations

Drug combination may be highly effective in recurrent ovarian cancer

Date:
June 1, 2014
Source:
Dana-Farber Cancer Institute
Summary:
Significant improvement with the use of a combination drug therapy for recurrent ovarian cancer has been identified by recent research. The trial compared the activity of the combination of the drug olaparib, which blocks DNA repair, and the blood vessel inhibitor drug cediranib, vs. olaparib alone. Trial results showed a near doubling of progression-free survival benefit for the combination therapy over use of the single drug alone.

Significant improvement with the use of a combination drug therapy for recurrent ovarian cancer was reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago today. This is the first ovarian cancer study to use a combination of drugs that could be taken orally. The drugs were tested in a phase I combination study followed by a randomized phase 2 trial sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health.

The trial compared the activity of the combination of the drug olaparib, which blocks DNA repair, and the blood vessel inhibitor drug cediranib, vs. olaparib alone. Trial results showed a near doubling of progression-free survival benefit for the combination therapy over use of the single drug alone.

"The findings of this study are exciting because they support the idea that combining these two targeted oral therapies results in significant activity in ovarian cancer, more so than olaparib alone," said Joyce Liu, M.D., MPH, the lead investigator and medical oncologist at the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, Boston. "We are looking forward to further exploring this combination in ovarian cancer and potentially increasing effective treatment options for our patients with this cancer."

There are over 22,000 cases of ovarian cancer diagnosed annually in the United States alone. Seventy-five percent of these cases are classified as high grade serous type, and they show more advanced disease at diagnosis and are more aggressive. Of this high-grade type, about three-quarters will regress after initial treatment but nearly all will recur and need follow-up treatment. That treatment will be based on how the cancers have responded to previous therapies and are broken down into two categories:

• Platinum-Sensitive -- these are patients most likely to benefit from PARP inhibition. PARP (Poly ADP-Ribose Polymerase) inhibitors, such as olaparib, are targeted drugs that block an enzyme involved in many functions in the cell, including the repair of DNA damage.

• Platinum-Resistant -- these are patients whose disease recurred within six months of conventional chemotherapy (using the drugs cisplatin or carboplatin) and are generally less responsive to subsequent treatments and have not responded as well to PARP inhibitors. They are currently treated with non-platinum chemotherapy, single-agents, with or without addition of the blood vessel inhibitor drug called bevacizumab.

An anti-angiogenic agent, or blood vessel inhibitor, called cediranib (which inhibits a protein known as VEGFR) and olaparib, a PARP inhibitor, are each clinically active in recurrent ovarian cancer. Pre-clinical studies suggest these agents add to and enhance the activity of each other, and a phase 1 study showed that the combination of cediranib and olaparib was well-tolerated with minimal side-effects. Hence, a total of 90 patients from nine centers were randomly assigned to one of two study arms for the phase II clinical trial: the first taking capsules of olaparib (400 mg twice daily) and the other taking a combination of the two drugs (200 mg olaparib in capsule-form twice daily and 30 mg tablets of cediranib once daily). The study arms were stratified by BRCA gene mutation status and receipt of prior anti-angiogenic therapy.

Patients, whose median age was 58, were enrolled from October 2011 to June 2013. As of March 2014, median progression-free survival was 9.2 months for olaparib and 16.7 months for the combination therapy, which is a significant advantage. The overall rate of toxicity was higher for patients on the combination therapy. Fatigue, diarrhea, and hypertension were the most common toxic effects, all of which were manageable.

"Of particular note is the fact that both drugs used in this trial are in pill form," said Percy Ivy, M.D., associate chief of NCI's Investigational Drug Branch. "Therefore, this therapy could be used anywhere in the world where patients can be monitored for dehydration due to diarrhea side-effects and blood pressure due to hypertension side-effects."

Based on these results, two phase 3 trials are being planned for platinum-sensitive and platinum-resistant ovarian cancer patients by one of NCI's new National Cancer Trial Network Groups, the NRG Oncology Group (formerly 3 cooperative groups: the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group (GOG).


Story Source:

The above story is based on materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.


Cite This Page:

Dana-Farber Cancer Institute. "Drug combination may be highly effective in recurrent ovarian cancer." ScienceDaily. ScienceDaily, 1 June 2014. <www.sciencedaily.com/releases/2014/06/140601113947.htm>.
Dana-Farber Cancer Institute. (2014, June 1). Drug combination may be highly effective in recurrent ovarian cancer. ScienceDaily. Retrieved September 15, 2014 from www.sciencedaily.com/releases/2014/06/140601113947.htm
Dana-Farber Cancer Institute. "Drug combination may be highly effective in recurrent ovarian cancer." ScienceDaily. www.sciencedaily.com/releases/2014/06/140601113947.htm (accessed September 15, 2014).

Share This



More Health & Medicine News

Monday, September 15, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Respiratory Virus Spreads To Northeast, Now In 21 States

Respiratory Virus Spreads To Northeast, Now In 21 States

Newsy (Sep. 14, 2014) The respiratory virus Enterovirus D68, which targets children, has spread from the Midwest to 21 states. Video provided by Newsy
Powered by NewsLook.com
Shocker: Journalists Are Utterly Addicted To Coffee

Shocker: Journalists Are Utterly Addicted To Coffee

Newsy (Sep. 13, 2014) A U.K. survey found that journalists consumed the most amount of coffee, but that's only the tip of the coffee-related statistics iceberg. Video provided by Newsy
Powered by NewsLook.com
Contagious Respiratory Illness Continues to Spread Across U.S.

Contagious Respiratory Illness Continues to Spread Across U.S.

Reuters - US Online Video (Sep. 12, 2014) Hundreds of children in several states have been stricken by a serious respiratory illness that is spreading across the U.S. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Ebola Batters Sierra Leone Economy Too

Ebola Batters Sierra Leone Economy Too

Reuters - Business Video Online (Sep. 12, 2014) The World Health Organisation warns that local health workers in West Africa can't keep up with Ebola - and among those countries hardest hit by the outbreak, the economic damage is coming into focus, too. As David Pollard reports, Sierra Leone admits that growth in one of the poorest economies in the region is taking a beating. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

    Technology News



    Save/Print:
    Share:

    Free Subscriptions


    Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

    Get Social & Mobile


    Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

    Have Feedback?


    Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
    Mobile: iPhone Android Web
    Follow: Facebook Twitter Google+
    Subscribe: RSS Feeds Email Newsletters
    Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins