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:6/25/2016)... ... 2016 , ... Conventional wisdom preaches the benefits of moderation, whether it’s a ... the bar too high can result in disappointment, perhaps even self-loathing. However, those who ... , Research from PsychTests.com reveals that behind the tendency to set ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... June 19, ... the dangers associated with chronic pain and the benefits of holistic treatments, Serenity ... who are suffering with Sickle Cell Disease. , Sickle Cell Disease (SCD) is a ...
(Date:6/24/2016)... MIAMI, Fla. (PRWEB) , ... June 24, 2016 , ... ... Florida Trend magazine’s 2016 Legal Elite. The attorneys chosen by their peers for this ... of Florida. , Seven Greenberg Traurig Shareholders received special honors as members of this ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... Topical BioMedics, Inc, makers of Topricin and ... that call for a minimum wage raise to $12 an hour by 2020 and then ... will restore the lost value of the minimum wage, assure the wage floor does not ...
(Date:6/24/2016)... ... June 24, 2016 , ... The ... recognize Dr. Barry M. Weintraub as a prominent plastic surgeon and the network’s ... the world, and the most handsome men, look naturally attractive. Plastic surgery should ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016 Research ... World Market for Companion Diagnostic Tests" report to their ... Market for Companion Diagnostics The World Market ... and personalized medicine diagnostics. Market analysis in the report includes ... Test Market (In Vitro Diagnostic Kits) by Region (N. America, ...
(Date:6/23/2016)... , June 23, 2016  MedSource announced ... as its e-clinical software solution of choice.  This ... best possible value to their clients by offering ... The preferred relationship establishes nowEDC as the EDC ... for MedSource,s full-service clients.  "nowEDC has long been ...
(Date:6/23/2016)... 23, 2016 Roche (SIX: RO, ROG; OTCQX: ... its Elecsys BRAHMS PCT (procalcitonin) assay as a dedicated ... shock. With this clearance, Roche is the first IVD ... solution for sepsis risk assessment and management. ... and PCT levels in blood can aid clinicians in ...
Breaking Medicine Technology: