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Phase I study of temsirolimus, capecitabine appears safe; positive survival trend seen

May18
2012
Leave a Comment Written by Joe Lovrek
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ScienceDaily (May 16, 2012) — A phase I clinical trial examining the safety of combining temsirolimus and capecitabine in advanced malignancies suggests the two agents can be given safely to patients. In addition, the Georgetown Lombardi Comprehensive Cancer Center researchers conducting the study in cancer patients whose tumors have resisted multiple treatments say the combination demonstrates “promising evidence” of disease control and should be studied in a phase II trial.

Their clinical findings and additional data from the study will be presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, June 1 through 5, 2012.

Temsirolimus is an mTOR inhibitor, meaning it stops mTOR from doing its job inside a cell. mTOR controls parts of a cell’s machinery, including the production of proteins, and it is essential for cancer cell growth. However, researchers know it’s not enough to stop one cellular mechanism in the vast majority of cancers. They hypothesize that by adding a chemotherapy, capecitabine, to temsirolimus, the combination will overwhelm the cancer cells and cause them to die.

Thirty-two patients with advanced cancers volunteered to participate in the phase I study of temsirolimus and capecitabine. The men and women had received an average of four previous types of treatments. The study was designed to examine the safety of various combination doses among the patients. Side effects were assessed in 30 patients.

The most common adverse events were mucositis (inflammation and ulceration of the mucous membranes lining the digestive tract), and hypophosphatemia (low level of phosphorus in the blood causing bone pain, confusion and muscle weakness). The most common serious adverse events were fatigue (4), diarrhea (2) and hypophosphatemia (2). For 16 of 30 patients, the dose of capecitabine was lowered to help alleviate side effects.

Of the 25 patients evaluable for the effectiveness of the combination, there were no partial responses or complete responses observed, but 14 patients had stable disease (no growth) — some with stable disease for more than six months. The median time to progression was three months with a median overall survival of seven months.

“We’re not surprised by the safety profile of this combination,” says the principal investigator, Michael Pishvaian, M.D., Ph.D., a gastrointestinal cancer specialist at Georgetown Lombardi. “While phase I studies are not designed to measure the tumor’s response to a drug or combination of drugs, it is encouraging when we see some clinical benefit. Looking ahead, I anticipate this combination will be studied in phase II trial for colon cancer patients who have exhausted all options for treatments.”

In addition to Pishvaian, other authors include Hongkun Wang, Ph.D., Rose Hardesty, RN John Deeken, M.D., A. Ruth He, M.D., Ph.D., Deepa Subramaniam, M.D., Tingting Zhuang, M.S., Damian L. McCarthy, B.S. Heather Melville, B.S. Chris Albanese, Ph.D., John L Marshall, M.D., and Jimmy Hwang, M.D.

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The above story is reprinted from materials provided by Georgetown University Medical Center.

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Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Posted in Cancer News

Hormone-depleting drug shows promise against localized high-risk prostate tumors

May18
2012
Leave a Comment Written by Joe Lovrek
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ScienceDaily (May 16, 2012) — A hormone-depleting drug approved last year for the treatment of metastatic prostate cancer can help eliminate or nearly eliminate tumors in many patients with aggressive cancers that have yet to spread beyond the prostate, according to a clinical study to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO), June 1-5 in Chicago.

The phase II clinical trial, led by investigators at Dana-Farber Cancer Institute and other research centers, examined the use of the drug abiraterone acetate (Zytiga®) in combination with prednisone and surgery in 58 men with high-risk prostate cancer isolated to the prostate gland. Participants received either three or six months of the two-drug regimen followed by surgery to remove the prostate. When the treatment was complete, pathology exams showed that one-third of the participants had no or almost no tumor tissue left.

“Very high-risk cancers localized to the prostate are rarely cured by prostatectomy alone,” says the study’s lead author, Mary-Ellen Taplin, MD, of Dana-Farber. “Therapies that combine surgery with older androgen-inhibiting drugs have not historically improved outcomes. This unmet need has given rise to efforts to develop new drugs capable of more completely reducing androgen levels within the prostate tumors.”

Androgen, the male hormone, provides the fuel for prostate cancer growth. Conventional therapies target androgen production in the testes and adrenal glands, but not within the tumor itself. Abiraterone acetate is capable of blocking androgen production in all three sites.

In the study, researchers used half the dose of prednisone (a steroid) standardly given with abiraterone acetate. This lower dose, it is hoped, would reduce the side effects associated with steroids while maintaining its benefits of protecting particular steroid imbalances associated with abiraterone. Since there were no increased side effects from abiraterone, the researchers feel that the lower dose of prednisone (5mg daily) is adequate for most patients.

“Most of the patients in this study had large tumors, high-grade prostate cancers and were at high risk for cancer spread,” Taplin remarks. “We’re very encouraged by the results and have begun another phase II study investigating another novel androgen signaling inhibitor, MDV3100, in the neoadjuvant setting for high-risk prostate cancer. We are also developing a clinical trial program investigating the addition of the investigational drug ARN509 to abiraterone. To prove the overall benefit of intensive androgen deprivation treatment in conjunction with prostatectomy, a large randomized clinical trial will need to be done.”

The research was funded in part by Janssen Research Development and The Prostate Cancer Foundation (PCF). The clinical trial was performed through the Prostate Cancer Clinical Trial Consortium, which is funded by the Department of Defense and PCF.

In addition to Taplin, the study’s other authors included researchers from Dana-Farber; Fred Hutchinson Cancer Research Center; University of Washington School of Medicine; Beth Israel Deaconess Medical Center; Brigham and Women’s Hospital; M.D. Anderson Cancer Center; and Janssen Research Development.

Taplin will present the data on June 2.

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The above story is reprinted from materials provided by Dana-Farber Cancer Institute.

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Posted in Cancer News

Google goes cancer: Search engine algorithm finds cancer biomarkers

May18
2012
Leave a Comment Written by Joe Lovrek
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ScienceDaily (May 17, 2012) — The strategy used by Google to decide which pages are relevant for a search query can also be used to determine which proteins in a patient’s cancer are relevant for the disease progression. Researchers from Dresden University of Technology, Germany, have used a modified version of Google’s PageRank algorithm to rank about 20,000 proteins by their genetic relevance to the progression of pancreatic cancer. In their study, published in PLoS Computational Biology, they found seven proteins that can help to assess how aggressive a patient’s tumor is and guide the clinician to decide if that patient should receive chemotherapy or not.

The researcher’s own version of the Google algorithm has been used in this study to find new cancer biomarkers, which are molecules produced by cancer cells. Biomarkers can help to detect cancer earlier in body fluids or directly in the cancer tissue obtained in an operation or biopsy. Finding these biomarkers is often difficult and time consuming. Another problem is that markers found in different studies for the same types of cancer almost never overlap.

This problem has been circumvented using the Google strategy, which takes into account the content of a web page and also how these pages are connected via hyperlinks. With this strategy as the model, the authors made use of the fact that proteins in a cell are connected through a network of physical and regulatory interactions; the ‘protein Facebook’ so to speak.

“Once we added the network information in our analysis, our biomarkers became more reproducible,” said Christof Winter, the paper’s first author. Using this network information and the Google Algorithm, a significant overlap was found with an earlier study from the University of North Carolina. There, a connection was made with a protein which can assess aggressiveness in pancreatic cancer.

Although the new biomarkers seem to mark an improvement over currently used diagnostic tools, they are far from perfect and still need to be validated in a larger follow-up study before they can be used in clinical practice. It remains an open problem to turn these insights into novel drugs which slow down cancer progression. A first step in this direction is the group’s cooperation with the Dresden-based biotech company RESprotect, who are running a clinical trial on a pancreas cancer drug.

TU Dresden is a leading German university, whose Center for Regenerative Therapies was awarded excellence status in the national excellence initiative. The work was a cooperation between the bioinformatics group of Prof. Dr. Michael Schroeder and the medical groups of Dr. Christian Pilarsky and Prof. Robert Grützmann.

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Journal Reference:

  1. Christof Winter, Glen Kristiansen, Stephan Kersting, Janine Roy, Daniela Aust, Thomas Knösel, Petra Rümmele, Beatrix Jahnke, Vera Hentrich, Felix Rückert, Marco Niedergethmann, Wilko Weichert, Marcus Bahra, Hans J. Schlitt, Utz Settmacher, Helmut Friess, Markus Büchler, Hans-Detlev Saeger, Michael Schroeder, Christian Pilarsky, Robert Grützmann. Google Goes Cancer: Improving Outcome Prediction for Cancer Patients by Network-Based Ranking of Marker Genes. PLoS Computational Biology, 2012; 8 (5): e1002511 DOI: 10.1371/journal.pcbi.1002511

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Posted in Cancer News
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