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.

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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."

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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.

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"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.

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New molecular imaging agent targets cornerstone of cancerous tumors

ScienceDaily (June 13, 2011) — A study introduced at SNM's 58th Annual Meeting may lead to the next wave of cancer imaging by helping to develop a molecular imaging agent that detects many malignant cancers' incessant development of blood vessels -- a process called angiogenesis. A protein biomarker known as CD105 has been shown to indicate tumor angiogenesis in cancer patients.

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"Non-invasive molecular imaging is a critical component of 21st century personalized medicine, and one of the hallmarks of cancer is angiogenesis," says Weibo Cai, PhD, assistant professor of radiology, medical physics and biomedical engineering at the University of Wisconsin-Madison's School of Medicine and Public Health. "CD105 is considered by many to be the best biomarker for evaluating tumor angiogenesis. Non-invasive imaging of this protein's expression could potentially play a variety of roles in the future of cancer patient management. CD105-targeted imaging agents also represent a new paradigm for the assessment of cancer therapies that target tumor angiogenesis. Applications for this agent could reach far beyond cancer and open many new avenues for future research."

Malignant cancers are defined by their ability to grow like weeds, forming fast and strong networks of blood vessels that carry oxygen and nutrients to the cancer's insatiable cellular structure. Endoglin, or CD105, is a naturally occurring protein that resides on the cell's surface. Above-normal expression of this protein is associated with poor cancer prognosis in more than 10 solid tumor types. The clinical standard for evaluating tumor angiogenesis is microvessel density (MVD) analysis, which is conducted by staining CD105 in tumor tissues that have been obtained by either surgical removal or biopsy. This study represents the first of its kind to report preliminary data on the non-invasive imaging of CD105 expression with positron emission tomography (PET), which provides a reliable measure of angiogenesis in the tumor.

Researchers used the medical isotope Copper-64 (64Cu) to label an antibody called TRC105, which binds to CD105. The full name of the agent is (64)Cu-DOTA-TRC105. The TRC105 antibody is currently being studied in a U.S. multicenter phase 1 human trial and multiple phase 2 therapy trials are planned or already underway for a range of cancer types. The current study specifically marks the effectiveness of using 64Cu-DOTA-TRC105 to gauge tumor angiogenesis. Results of the study showed this PET imaging agent to be highly effective, with rapid and persistent CD105-targeted uptake by tumors in mice.

Not only could this potentially be a turning point for cancer imaging and therapy, but some other major causes of death like heart attack, stroke and atherosclerosis also actively demonstrate the over-expression of CD105. Molecular imaging of this protein could one day lead to expanded tools for the detection and treatment of any number of diseases characterized by enhanced angiogenesis.

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