Navigation Links
Late-stage ovarian cancer shows promise in two-drug phase I trial

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
Indiana University School of Medicine

Related medicine news :

1. Late-stage melanoma results in economic burden
2. Cancer Drug Safe for Late-Stage Pelvic Disease
3. Study Finds Possible Explanation for the Link Between Infertility and Breast/Ovarian Cancer Risks
4. Symptoms have little value for early detection of ovarian cancer
5. Symptoms Alone Dont Spot Ovarian Cancer Early
6. Ultrasound plus proteomic blood analyses may help physicians diagnose early-stage ovarian cancer
7. Abbott Receives European Regulatory Approval for New Ovarian Cancer Diagnostic Test
8. Possible ovarian cancer treatment target identified
9. Arrayit Diagnostics to Bring First Pre-Symptomatic Ovarian Cancer Blood Test to Multi-Billion Dollar Diagnostic Market in 2010
10. Research suggests link between infertility, low egg reserve, and breast/ovarian cancer gene (BRCA1)
11. How to make the best decisions when at high risk for breast or ovarian cancer
Post Your Comments:
(Date:11/30/2015)... ... November 30, 2015 , ... In an effort to ... to access life-saving information provided directly from top experts in mesothelioma, in 2016 ... conferences in three major cities: Houston, San Francisco, and Chicago. , “For ...
(Date:11/30/2015)... Los Angeles, CA (PRWEB) , ... November 30, 2015 , ... ... hunger cravings that drive people to overeat are not necessarily caused by real hunger, ... brain that the stomach needs food. He notes that, while many patients are aware ...
(Date:11/30/2015)... FL (PRWEB) , ... November 30, 2015 , ... ... a comparison chart and ingredient list of its hemorrhoid ointment to its website. ... effective pain relief for people suffering from hemorrhoids. Adding the comparison chart and ...
(Date:11/30/2015)... ... November 30, 2015 , ... Using a combination of two blood sugar tests ... adults, according to a new study by researchers at the School of Public Health ... Adults: Using Combinations of Blood Glucose Tests ,” published in Frontiers in Public Health, ...
(Date:11/30/2015)... ... November 30, 2015 , ... The recently published 32nd Annual ... (NPDS) reveals that in 2014, someone called a poison center about every 11 ... which were human exposure cases. , The American Association of Poison Control Centers ...
Breaking Medicine News(10 mins):
(Date:11/30/2015)... Medical Systems (NYSE: VAR ) has signed a Memorandum of ... the largest hospital chain in India , to ... country. The MoU was signed by Dr. K. Prabakar , ... Varian,s India managing director, in ... intends to deploy its Access to Care program by leveraging the ...
(Date:11/30/2015)... , Nov. 30, 2015   VolitionRx Limited (NYSE ... diagnostic tests for a broad range of cancer types and ... LD Micro Conference, which will be held December 1 - 3 ... from VolitionRx will be David Kratochvil , Chief Financial ... of Investor Relations. ® blood-based tests for ...
(Date:11/30/2015)... -- Mexico Healthcare and Life Sciences Report 2015 . ... --> Pharmaboardroom releases its new 98-page Mexico Healthcare ... , a country of over 122 million people. --> ... million people. --> It offers companies, investors, policymakers, and ... into the second largest pharma and healthcare market in ...
Breaking Medicine Technology: