Navigation Links
Late-stage ovarian cancer shows promise in 2-drug phase I trial
Date:6/10/2010

INDIANAPOLIS -- The combination of decitabine and carboplatin appears to improve the outcome of women who have late-stage ovarian cancer. In an upcoming issue of the journal Cancer (online today), Indiana University researchers report four of 10 patients who participated in a phase I clinical trial had no disease progression after six months of treatment. One patient experienced complete resolution of tumor tissue for a period of time.

Advanced ovarian cancer is often diagnosed too late for treatment to be effective. Patients are often told they have virtually no chance of recovery and only months to live.

Women participating in the study were between 51 and 71, and had previously exhausted all approved treatments for ovarian cancer. They enrolled in an Indiana University Melvin and Bren Simon Cancer Center clinical trial designed to increase their sensitivity to the commonly prescribed ovarian cancer drug, platinum-based carboplatin.

Women with ovarian cancer usually survive less than one year after they become resistant to carboplatin and their cancer recurs, said co-principal investigator Daniela Matei, M.D., an associate professor of medicine at the Indiana University School of Medicine. Matei led the clinical portion of the trial.

"Carboplatin is the most efficient drug therapy for ovarian cancer," Matei said. "Unfortunately, patients with recurrent disease become resistant to the drug after one or two rounds."

Decitabine was first used to treat the study patients intravenously daily for five days followed on the eighth day with carboplatin. After a month, the regimen begins again.

Six months after the trial began, four of the patients had no disease progression. At eight-and-a-half months, seven patients were alive (and at press time, still alive). Cancerous tissue in one of the patients shrank completely.

Adverse reactions to the treatment regiments were mild, including nausea, fatigue, and neutropenia (reduced white blood cell count).

Encouraged by the results of the phase I trial, which determined the safety of two different dosing regimens, a phase II trial is now under way with 17 patients already enrolled. Phase II trials are primarily focused on assessing the effectiveness of a drug or treatment protocol.

The study's other co-principal investigator, Kenneth Nephew, geneticist in the IU Medical Sciences Program-Bloomington, led the report's biochemical and DNA analysis.

In a bid to resensitize patients to carboplatin, Nephew and Matei and co-investigator Jeanne M. Schilder, M.D., associate professor of obstetrics and gynecology in the Division of Gynecologic Oncology at the IU School of Medicine, turned to the DNA demethylating agent, decitabine.

Why trial patients were responsive to the combination of decitabine and carboplatin is not yet known, but based on the literature and an analysis of biopsy tissue and blood samples, Nephew and Matei suspect decitabine reactivates tumor suppression genes that are turned off in ovarian cancer cells.

One of the hallmarks of ovarian cancer is the aberrant methylation of cytosine, one of DNA's four nitrogenous bases. Methylation prevents DNA readers from expressing genes. Some of the silenced genes won't be terribly important, but some, like tumor suppression genes, are. Decitabine is a known methylation inhibitor that can help return tumor suppression genes to an active state, and also improve cells' susceptibility to anti-cancer drugs like carboplatin.

"Our hypothesis is that decitabine isn't just targeting active ovarian cancer cells, but also cancer stem cells that seem to survive the first treatments," Nephew said. "By keeping tumor suppression genes from being methylated, carboplatin and other platinum-based treatments for ovarian cancer have a better chance of success in the late stages."

The researchers also reported that decitabine appears to have caused six of the 10 patients to become hypersensitive to carboplatin (a mild allergic reaction, treatable with steroids). While Nephew and Matei say that the effect may not be observed in a larger patient population, the scientists say they are intrigued by the phenomenon.


'/>"/>

Contact: Mary L. Hardin
mhardin@iupui.edu
317-274-7722
Indiana University School of Medicine
Source:Eurekalert

Related medicine news :

1. Late-stage ovarian cancer shows promise in two-drug phase I trial
2. Cancer Drug Safe for Late-Stage Pelvic Disease
3. Late-stage melanoma results in economic burden
4. New treatment regimen shown effective against advanced ovarian cancer
5. Early Detection of Ovarian Cancer Moves Closer
6. CA-125 change over time shows promise as screening tool for early detection of ovarian cancer
7. PMH cancer researchers link ovarian hormone to breast stem cells growth
8. Study Makes Strides in Understanding Ovarian Cancer
9. Researchers identify a new breast and ovarian cancer susceptibility gene
10. Ovarian cancer study offers vital clues for new therapies
11. Only women with Western Swedish breast cancer gene run higher risk of ovarian cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/20/2017)... ... January 20, 2017 , ... Source Vitál Apothecary, a skin ... pure essential oils, announced the company had a successful visit to the 2017 ECRM ... event gives companies that work in the nutritional, sports and health industries a chance ...
(Date:1/20/2017)... ... , ... Lice Troopers, the lice removal company based in South Florida, has ... holiday season. , “It happens every year around this time,” says owner, Arie ... which is the head-to-head gateway that lice need to spread.” , As children return ...
(Date:1/20/2017)... ... ... Michael and Betsy Brauser celebrated 5 years of Betsy’s participation in a ... has been life-saving as she has been on the trial for more than six ... ovarian cancer in 2009. She underwent standard chemotherapy but a year later went to ...
(Date:1/20/2017)... ... January 20, 2017 , ... “Mary Magdalene: Grace is ... life of the woman who witnessed Jesus Christ firsthand. “Mary Magdalene: Grace is Greater ... spent her career as an educator interacting with countless women who had little knowledge ...
(Date:1/20/2017)... ... ... fine examination of how God handles sin, including how to let go of lingering guilt ... over ten long years has been waiting to release this powerful insight about forgiveness that ... serving the Lord for over twenty years, and he has been preaching and teaching the ...
Breaking Medicine News(10 mins):
(Date:1/19/2017)... , Jan. 19, 2017 Many patients ... for their medication when a pharmacy just a few ... prescription.  To alleviate this problem Medicationdiscountcard.com has ... to see exactly how much their medication will cost ... Made Easy Medicationdiscountcard.com ...
(Date:1/19/2017)... Calif. , Jan. 19, 2017  Abaxis, Inc. ... manufacturing point-of-care blood analysis instruments and consumables for the ... call to discuss its financial results for the third ... call will be at 4:15 p.m. ET on Thursday, ... for the third quarter fiscal year 2017 after the ...
(Date:1/19/2017)... ALTO, Calif. , Jan. 19, 2017   ... research, is excited to announce that the first ... Cancer Biology  (RP:CB) have been published in eLife ... this project represents the first practical evaluation of ... result in reproducible studies. Unlike other assessments of ...
Breaking Medicine Technology: