Novel experimental agent is highly active in CLL patients, interim study shows

ScienceDaily (June 3, 2011) — An interim analysis of a phase II clinical trial indicates that a novel experimental agent for chronic lymphocytic leukemia (CLL) is highly active and well tolerated both in patients who are undergoing treatment for the first time and those who have relapsed and are resistant to other therapy.

See Also:Health & MedicineToday's HealthcareLeukemiaDiseases and ConditionsWounds and HealingPersonalized MedicineMultiple Sclerosis ResearchReferenceClinical trialLeukemiaDouble blindPulmonary embolism

The agent, called PCI-32765, is the first drug designed to target Bruton's tyrosine kinase, whose function is essential for CLL-cell survival and proliferation.

Study leader Dr. John C. Byrd, director of the division of hematology at Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James) presented the findings June 5 at the 2011 American Society of Clinical Oncology annual meeting in Chicago.

The analysis involved the first 21 cases in the untreated-patient group and the first 27 individuals in the relapsed/refractory-patient group. One patient in each group had a complete remission, and 13 patients (62 percent) in the previously untreated group and 12 patients (44 percent) in the relapsed group had partial remissions.

"We are excited about these early findings because they suggest that PCI-32765 is a highly active oral therapeutic that produces a high rate of durable remissions -- the remissions last months on end -- with acceptable toxicity in relapsed and refractory CLL," Byrd says.

Complete remission means there is no detectable CLL in anywhere in the body; partial remission means that the individual's disease volume has decreased 50 percent or more in a sustained manner.

"It is exciting to see a drug that was shown to be active in the laboratory translate to clinical benefit for CLL patients," says researcher Dr. Amy Johnson, assistant professor of medicine at the OSUCCC -- James. Johnson co-led the pre-clinical CLL work at Ohio State with Byrd and now coordinates several correlative studies for this clinical trial.

Byrd stresses that the patients show several benefits of the treatment, such as higher platelet counts and hemoglobin levels, and that many report that they feel dramatically better overall with less fatigue, factors that are difficult to measure and report as a number.

"These responses last for many months in part because patients are willing to remain on the drug since the side effects are very tolerable," he notes.

The ongoing phase II clinical trial involves 78 patients with previously untreated or relapsed and refractory CLL or small lymphocytic leukemia. The previously untreated patients were all age 65 or older; individuals in the relapsed group all had two or more earlier treatments followed by recurrent disease.

"These are early findings, so patients with partial remissions could improve to complete remissions with further observation," Byrd says. "Usually patients with highly resistant and refractory CLL would have progressed and possibly died by this time, but 85 percent remain on PCI-32765 and continue to improve."

Email or share this story:

Novel imaging agent targets breast tumor development

ScienceDaily (June 6, 2011) — Scientists presented new research at SNM's 58th Annual Meeting that has the potential to help physicians detect breast cancer by imaging the proliferation of blood vessels carrying oxygen and nutrients to breast tumors. Their study is evaluating a new imaging agent that is naturally drawn to angiogenesis -- the development of new blood vessels in tissues both normal and cancerous. This process turns malignant during the growth stage of many cancerous tumors including those in breast tissue.

See Also:Health & MedicineBreast CancerMedical ImagingCancerWomen's HealthBrain TumorBreastfeedingReferenceMetastasisInterventional radiologyPositron emission tomographyMammography

"The positive outcomes of this study are encouraging and may provide clinicians with additional information for breast cancer management," says Andrei Iagaru, MD, lead author of the study and assistant professor of radiology and nuclear medicine at Stanford University Medical Center, Stanford, Calif. "PET imaging with this agent could potentially lead to better clinical decisions; patients with progressive cancer who are ideal candidates for aggressive therapies could be identified earlier to improve their prognosis."

The new imaging agent central to this study is called 18F FPPRGD2, which combines the medical isotope fluorine-18 (18F) with a protein biomarker ideal for imaging the expression of an integrin known as αvβ3. Integrins are essentially protein-based receptors that regulate the adhesion between cells and connecting tissues. They are also involved in cell signaling, which mediates a cell's shape, movement and lifecycle, but their most useful trait is their key involvement in angiogenesis. Upon injection the agent seeks out tissues in a state of angiogenesis and is then captured using a molecular imaging technique known as positron emission tomography (PET), which produces functional imaging of the body.

Six female participants with breast cancer were recruited for the study and were imaged twice using 18F FPPRGD2 and 18F FDG PET/CT within two weeks. PET imaging with 18F FPPRGD2 showed superior functionality for identifying angiogenesis in breast tissue, with strong uptake and distribution in both primary cancers and metastatic lesions.

Further studies evaluating the effectiveness of 18F FPPRGD2 for targeting breast tumor angiogenesis could lead to its availability for clinical use for patients known to have breast cancer. This agent could be an effective tool for cancer staging and may improve patient treatment planning as a result of the information it provides. Preliminary findings show that it could become a useful weapon in the fight against breast cancer.

Email or share this story:

New clinical trial to test novel approach to treat triple-negative breast cancer

ScienceDaily (June 2, 2011) — A multicenter clinical trial led by a researcher at the University of Maryland Marlene and Stewart Greenebaum Cancer Center will evaluate a new approach to treat triple-negative breast cancer, an often-aggressive type of cancer that is more common among African-Americans and young women. The study will help researchers determine if an experimental drug, entinostat, can reprogram tumor cells to express a protein called an estrogen receptor to make them sensitive to hormone therapy.

See Also:Health & MedicineBreast CancerCancerLung CancerColon CancerProstate CancerBrain TumorReferenceMetastasisBreast cancerTumor suppressor geneHormone replacement therapy

Saranya Chumsri, M.D., an oncologist at the Greenebaum Cancer Center and assistant professor of medicine at the University of Maryland School of Medicine, is the principal investigator of the newly opened National Cancer Institute-funded study. The trial is based on laboratory studies by Angela H. Brodie, Ph.D., an internationally recognized University of Maryland breast cancer researcher, and her colleagues. Their research, recently published in the journal Cancer Research, found that entinostat can cause triple-negative breast cancer cells to become sensitive to a hormone therapy such as an aromatase inhibitor. Dr. Brodie pioneered the development of aromatase inhibitors, a class of breast cancer drugs that reduces the level of estrogen produced by the body, thereby cutting off the fuel to cancer cells.

In this Phase II trial, doctors will treat newly diagnosed postmenopausal patients with entinostat and an aromatase inhibitor called anastrozole (Arimidex) before they have surgery to remove their cancer. Researchers will analyze tissue from the tumor and blood samples to evaluate whether the treatment is effective. After surgery, patients will receive standard treatment, such as chemotherapy and radiation.

"We hope that entinostat will make the tumor cells more sensitive to the drug anastrozole, causing the tumor to shrink or, at the very least, stop growing," Dr. Chumsri says. "For patients with triple-negative breast cancer, chemotherapy is currently the only drug treatment option, and it has a lot of side effects compared to hormone therapies like anastrozole."

Triple-negative breast cancer is unique in that it lacks three common receptors in the cell -- estrogen, progesterone or human epidermal growth factor 2 (HER2), which are the targets of drugs widely used today to treat breast cancer. As a result, this cancer can be very difficult to treat; it doesn't respond to therapies that target estrogen and progesterone receptors, such as tamoxifen (Nolvadex), fulvestrant (Faslodex) and aromatase inhibitors (Femara, Arimidex and Aromasin), or to HER2-targeted therapies such as trastuzumab (Herceptin) and lapatinib (Tykerb).

About 15 to 20 percent of breast cancers are triple-negative. For unknown reasons, there is a higher prevalence of this type of breast cancer among African-Americans, young women and women with the BRCA1 gene mutation. African-American women are twice as likely as white women to have this type of cancer, which can be very aggressive and spread to other parts of the body, such as the lungs, liver and brain.

The clinical trial is based on laboratory studies by Dr. Brodie, a professor of pharmacology and experimental therapeutics, and Gauri J. Sabnis, Ph.D., an assistant professor of pharmacology and experimental therapeutics, at the University of Maryland School of Medicine, in collaboration with Saraswati Sukumar, M.S., Ph.D., a professor of oncology and pathology at the Johns Hopkins University School of Medicine. Their research showed that entinostat can sensitize triple-negative breast cancer cells to treatment with an aromatase inhibitor, and when combined with an aromatase inhibitor, also reduce the growth and spread of tumors in animal models.

"Adding to her long list of remarkable achievements, Dr. Brodie has continued her research into aromatase inhibitors, searching for ways to overcome tumors' resistance to treatment," says E. Albert Reece, M.D., Ph.D., M.B.A., vice president of medical affairs at the University of Maryland and dean of the University of Maryland School of Medicine. "This multicenter clinical trial led by Dr. Saranya Chumsri is an excellent example of how our scientists turn discoveries made in the lab into new treatments that may benefit patients."

Entinostat is an oral, selective histone deacetylase (HDAC) inhibitor. This anti-cancer agent is being developed by Syndax Pharmaceuticals, Inc., and is being investigated in other clinical studies for the treatment of advanced estrogen receptor-positive breast cancer, advanced non-small-cell lung cancer, advanced colorectal cancer and Hodgkin's lymphoma.

Triple-negative breast cancer patients in this clinical trial will take entinostat weekly and anastrozole once daily for two to four weeks while they are waiting to have surgery. Researchers will use blood tests and tissue analysis of tumors to evaluate the effectiveness of the combination therapy.

Researchers hope to enroll a total of 41 patients at 20 sites, including the University of Maryland Greenebaum Cancer Center. The centers involved in the study are affiliated with the University of Chicago Phase II study research consortium and the California Cancer Consortium.

Dr. Chumsri says that if the results of this trial are positive, researchers plan to launch a larger study to test the combination therapy on women whose cancer has metastasized to other parts of the body. "These women have limited treatment options. Hopefully, this treatment would give them a longer period in which their cancer is not progressing, with only minimal side effects compared to chemotherapy," she says.

Email or share this story: