National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
August 10, 2010 • Volume 7 / Number 16

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NEWS

An echocardiogram showing a measurement of the heart's left ventricleProtein Helps Predict Cancer Therapy-induced Heart Damage

In a prospective study of 251 women with HER2-positive breast cancer, women with elevated blood levels of a protein called troponin I had significantly higher rates of cardiotoxicity (heart damage) during treatment with trastuzumab (Herceptin) than women who did not have elevated levels of troponin I before or during treatment. Women with elevated troponin I were also three times less likely to recover from the observed heart damage. The results came from a study led by Dr. Daniela Cardinale of the European Institute of Oncology in Milan, Italy, and were published online August 2 in the Journal of Clinical OncologyRead more > >

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NCI Cancer Bulletin Publication Break

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IN DEPTH

UPDATES

  • Legislative Update

    • Project Cancer Education: An Introduction to Translational Research at NCI
  • Cancer.gov Update

    • NCI Recovery Act Web Site Highlights Cancer Disparity Studies
  • Notes

    • NIH Intramural Research Program Is Recruiting Earl Stadtman Investigators
    • Office of China Cancer Programs Issues Report on Symposium
    • New Issue of OCG e-News Available

Selected articles from past issues of the NCI Cancer Bulletin are available in Spanish.

The NCI Cancer Bulletin is produced by the National Cancer Institute (NCI), which was established in 1937. Through basic, clinical, and population-based biomedical research and training, NCI conducts and supports research that will lead to a future in which we can identify the environmental and genetic causes of cancer, prevent cancer before it starts, identify cancers that do develop at the earliest stage, eliminate cancers through innovative treatment interventions, and biologically control those cancers that we cannot eliminate so they become manageable, chronic diseases.

For more information about cancer, call 1-800-4-CANCER or visit .

NCI Cancer Bulletin staff can be reached at ncicancerbulletin@mail.nih.gov.

Featured Article

Protein Helps Predict Cancer Therapy-induced Heart Damage

An echocardiogram showing a measurement of the heart's left ventricle. Echocardiography measurements of the heart's left ventricle help doctors monitor heart function during anticancer treatment. A reduction in left ventricle ejection fraction (LVEF) during treatment can indicate drug-induced heart damage. Click to Enlarge.

In a prospective study of 251 women with HER2-positive breast cancer, women with elevated blood levels of a protein called troponin I had significantly higher rates of cardiotoxicity (heart damage) during treatment with trastuzumab (Herceptin) than women who did not have elevated levels of troponin I before or during treatment. Women with elevated troponin I were also three times less likely to recover from the observed heart damage. The results came from a study led by Dr. Daniela Cardinale of the European Institute of Oncology in Milan, Italy, and were published online August 2 in the Journal of Clinical Oncology.

Measurement of troponin I levels “seems to allow us to distinguish patients with a more favorable cardiac outcome from those in whom close cardiologic monitoring is mandatory and for whom prophylactic strategies for prevention of…cardiotoxicity should be planned,” Dr. Cardinale and her colleagues wrote.

The new data add to the growing body of knowledge concerning the relationship between anthracycline-based chemotherapy, trastuzumab, and heart damage. Cardiotoxicity in patients receiving trastuzumab is more likely if they have had previous anthracycline treatment, and those patients treated with sequential anthracycline therapy and trastuzumab are less likely to recover cardiac function than patients not previously treated with this class of drugs. Anthracyclines cause heart damage through a well-understood pathway, and the Italian researchers had previously shown that elevated troponin I levels can predict chemotherapy-induced heart injury.

For the current study, the researchers prospectively enrolled 123 women receiving adjuvant trastuzumab for newly diagnosed breast cancer and 128 women receiving trastuzumab for metastatic breast cancer. All of the women had their left ventricular ejection fraction (LVEF)—a measurement of heart function—and troponin I concentrations evaluated before and during the study and during follow-up visits.

Patients who developed heart damage during the study discontinued trastuzumab and began heart failure treatment with the drugs enalapril and carvedilol, with additional heart treatments allowed as required. Doctors did not alter any patients’ treatment in response to changes in troponin I levels.

Overall, the researchers found elevated troponin I levels in 36 women, including 7 who had elevated levels even before trastuzumab treatment, most likely due to pre-existing heart damage from previous chemotherapy. In an analysis that looked at factors associated with risk for cardiac damage, including age, hypertension, high cholesterol, and smoking, elevated troponin I was the only independent predictor of heart damage during trastuzumab treatment, although previous treatment with an anthracycline neared statistical significance.

Sixty-two percent of the women who experienced trastuzumab-induced cardiotoxicity (TIC) had elevated troponin I levels during treatment. Sixty percent of all women with TIC recovered normal heart function after withdrawal of trastuzumab and treatment with heart-failure medications, but this recovery was not uniformly linked to low troponin I levels. While all of the women who did not recover heart function had elevated troponin I levels during treatment, 36 percent of women with elevated troponin recovered normal heart function.

Ninety percent of patients who experienced TIC had previously received chemotherapy with an anthracycline. The relationship between heart damage induced by these drugs is still being studied, explained Dr. Michael Ewer of the University of Texas M. D. Anderson Cancer Center and Dr. Steven Ewer of the University of Wisconsin, in an accompanying editorial.

One proposed explanation for the increased incidence of TIC in patients previously treated with anthracyclines is that trastuzumab by itself is not especially toxic to heart tissue, but that the drug aggravates anthracycline-induced heart damage by blocking HER2. HER2 is expressed in heart muscle as well as in breast tissue and may play a vital role in cardiac cellular repair mechanisms. Therefore, blocking HER2 may prevent the heart from repairing itself after exposure to anthracycline-based chemotherapy. “What we seem to be seeing is a modulating effect of trastuzumab on the vulnerable and previously damaged myocyte [heart muscle cell],” they wrote.

These results “are potentially very useful in terms of helping identify patients who may be at high risk for developing irreversible cardiac toxicity,” said Dr. Stanley Lipkowitz, senior investigator in the Laboratory of Cellular and Molecular Biology in NCI’s Center for Cancer Research and an attending physician at the National Naval Medical Center’s Breast Care Center. However, this relatively small study does have several limitations, he explained. Patients were treated in both the adjuvant and metastatic setting and with several different chemotherapy regimens. “It would be helpful to confirm the results in larger studies in each setting and ideally in studies where the chemotherapy is consistent,” he said.

In addition, Dr. Lipkowitz continued, longer-term follow-up is needed for women receiving adjuvant trastuzumab who have a longer life expectancy than women with metastatic disease. These women are at risk of late-stage side effects, and further research might refine the factors that predict TIC.

“Importantly, 10 out of 36 patients with elevated troponin I  during trastuzumab treatment did not develop cardiac toxicity, and 9 out of 26 patients with elevated troponin I and TIC during trastuzumab treatment recovered LVEF,” explained Dr. Lipkowitz. Additional studies are needed to confirm these results and to refine the levels or kinetics of troponin I elevation that correlate with cardiac outcomes, as well as how best to use such tests to guide treatment, he said.

—Sharon Reynolds

Cancer Research Highlights

Bone Drugs Do Not Appear to Increase Esophageal or Gastric Cancer Risk

Contrary to previous reports, researchers in the United Kingdom and at NCI have found no significant link at any level of use between oral bisphosphonates, drugs used to treat or prevent osteoporosis and bone-density loss, and esophageal or gastric cancer. The findings were published online August 10 in the Journal of the American Medical Association.

Dr. Chris Cardwell of Queen’s University Belfast and his colleagues analyzed medical data from more than 80,000 patients listed in the UK General Practice Research Database, half of who had been treated with bisphosphonates between 1996 and 2006 and half who had not used bisphosphonates. The patients were predominantly female (81 percent), with an average age of 70, and the follow-up time was 4.5 years for the bisphosphonate group and 4.4 years for the control group.

The rates of esophageal and gastric cancer were similar in both groups. Among the 41,826 people who took oral bisphosphonates, 116 developed gastric or esophageal cancer, compared with 115 people in the control group.

In January 2009, Dr. Diane Wysowski of the FDA urged caution when prescribing oral bisphosphonates to patients with preneoplastic lesions in the esophagus and called for studies of the association between bisphosphonates and esophageal cancer. However, in view of the new findings, “these drugs should not be withheld, on the basis of possible esophageal cancer risk, from patients with a genuine clinical indication for their use,” the researchers wrote.

Immune Cells’ Anticancer Abilities May Be Hampered by High Lipid Levels

In both mice and humans with cancer, dendritic cells, which are important components of the immune system, tend to have high lipid levels that significantly hamper their ability to direct other immune cells to attack cancer cells, a team of U.S. researchers reported. The research team also showed that a drug that interferes with the synthesis of these fat molecules restores dendritic cells’ ability to stimulate an antitumor response. The study was published in the August 2010 Nature Medicine.

Dendritic cells take up and process proteins and other molecules made by cancer cells (as well as viruses, bacteria, and other foreign bodies) and “present” them as antigens to other immune cells, so they can elicit an attack. Dr. Dmitry Gabrilovich from the H. Lee Moffitt Cancer Center and colleagues showed that dendritic cells in both mouse models of cancer and human tumor samples had significantly higher lipid levels—specifically triglycerides—than those from healthy mice and humans.

Dendritic cells with normal lipid levels generated a robust immune response, whereas the response generated by dendritic cells with elevated lipid levels was much weaker. Further experiments demonstrated that dendritic cells with elevated lipid levels had “profound defects” in their ability to take up and process antigen material, the researchers wrote.

In mice, treatment with a drug that interferes with the synthesis of fatty acids, called TOFA, “decreased the presence of lipid-laden dendritic cells" and restored their ability to “stimulate allogeneic T cells,” they reported. Combining a cancer vaccine with TOFA significantly shrank tumors, whereas the vaccines given alone had very little antitumor effect.

The findings suggest a new potential avenue for cancer immunotherapy, wrote Drs. Laurence Zitvogel and Guido Kroemer in an accompanying editorial. “Interfering with triglyceride accumulation in [dendritic cells] might constitute a promising strategy to restore anticancer immune responses and improve the efficacy of therapeutic vaccinations and conventional chemotherapies,” they concluded.

microRNA May Regulate Growth of Tumor Blood Vessels

The growth of blood vessels that supply tumors with essential nutrients may be regulated in endothelial cells by a small RNA molecule, or microRNA, a new study suggests. Researchers identified a microRNA called miR-132 that appears to act as a molecular switch for endothelial cell growth, causing the cells to transition out of their normal resting state and form new blood vessels (angiogenesis). The study, which could lead to a strategy for preventing angiogenesis and potentially for treating cancer, was published online by Dr. David Cheresh of the University of California, San Diego, and his colleagues August 1 in Nature Medicine.

Endothelial cells are among the least proliferative types of cells in adults, but they can be activated in response to certain cues, such as growth factors. Suspecting that microRNAs, which are known to regulate genes, might play a role, the researchers profiled microRNAs in a stem cell model of human vascular development and identified miR-132 as highly upregulated during the development of blood vessels. They then confirmed that miR-132 expression was also highly elevated in benign lesions of blood vessels, or hemangiomas, and in the blood vessels of human tumors, but was not detectable in normal blood vessels.

A molecular pathway analysis revealed that miR-132 suppresses the expression of a gene that encodes the protein p120RasGAP, which is a negative regulator of the protein Ras. Ras is frequently altered in cancer, so targeting miR-132 could be a way to intervene in an important pathway, the researchers said. And because miR-132 is found primarily in endothelial cells, these strategies would likely be specific to these cells, they noted.

As a proof of principle, the researchers used nanoparticle technologies they have developed to deliver an inhibitor of miR-132 directly to the vasculature of tumor-bearing mice. This treatment resulted in the blockade of tumor angiogenesis and tumor growth. Moreover, in mice with retinal disease that featured the growth of new blood vessels, direct injection of the anti-miR-132 into the eye was able to suppress angiogenesis in the retina.

“We essentially turned off the angiogenic switch during angiogenesis,” said Dr. Cheresh. The preponderance of growth in these cells was reduced, making it feasible to apply this kind of approach to patients with cancer and retinal diseases characterized by extensive angiogenesis, he added. 

Many U.S. and Canadian Oncologists Unprepared to Use Cost-effectiveness Data in Practice

Despite broad differences between their nation’s health care systems, Canadian and U.S. oncologists have similar opinions about how drug costs and comparative effectiveness should factor into decisions about patient care, report the authors of a recent survey. (The Canadian government funds health care, whereas the U.S. government does not.) The survey also revealed that oncologists in both countries do not feel adequately prepared to discuss treatment costs or comparative effectiveness with their patients. The results appeared online August 9 in the Journal of Clinical Oncology.

Nearly 800 randomly selected members of the American Society of Clinical Oncology took part in the survey, which was funded in part by the California HealthCare Foundation. In Canada, surveys were offered to members of national medical and oncology organizations, and 138 responses were received.

The survey showed that most physicians in both countries believe that patients should have access to effective cancer treatments only if the treatments provide a “good value for [the] money,” though significantly more Canadians felt this way than Americans (75 percent versus 58 percent, respectively). The threshold for a “good value” was higher for Canadians than for Americans, but most oncologists in both countries believe that a ratio of less than $100,000 per life-year gained was appropriate. However, less than half of the oncologists (42 percent of the Americans and 49 percent of the Canadians) felt prepared to factor cost-effectiveness into their treatment decisions.

Clinicians in both countries did not favor government or insurance companies making decisions about whether specific drugs provide good value, but they did favor physicians and nonprofits doing so; and the majority in both countries felt that more government price controls for cancer drugs are needed, though this opinion was less common in the United States (57 percent) than in Canada (68 percent).

The authors noted the possibility of biases in their results due to different survey methods used in each country. But they concluded that because the opinions of the two groups were so similar, and because oncologists in both countries face rapidly rising costs of new cancer medications that may or may not be covered by health insurers, oncologists in the United States and Canada should collaborate on strategies to face the challenges ahead.

Special Report

A Cancer Treatment That Sticks Around

The shells of shrimp are a source of chitosan, a compound used in a number of clinical settings. Chitosan is derived from the shells of crustaceans such as shrimp and lobsters. It is used in a number of clinical applications, including in bandages to help control bleeding.

A new study in mice may help revive the clinical prospects of the cytokine interleukin-12 (IL-12), a drug that stimulates the immune system to attack tumors. Based on the results of this study and an earlier study by the same group of researchers, a phase I clinical trial is being planned to test the treatment in patients with bladder cancer. The new study will be published in the September Journal of Immunotherapy.

IL-12, a protein that has been the subject of intense investigation for several decades, modulates important components of the immune system and has demonstrated dramatic antitumor effects in numerous laboratory and animal model studies. Its clinical development, however, has been stunted by significant toxicities seen in several human trials in which it was given intravenously or subcutaneously.

In an effort to circumvent that problem, Dr. John Greiner of the Laboratory of Tumor Immunology and Biology in NCI’s Center for Cancer Research and colleagues mixed IL-12 with a compound called chitosan, a biological adhesive that can bind synthetic or biological molecules to tissue. The resulting mixture was injected directly into a tumor.

Chitosan, which is a polysaccharide derived from the shells of crustaceans such as shrimp or lobster, is an important part of a “delivery system” that brings IL-12 “directly into the tumor environment,” explained Dr. Greiner. The treatment was not only effective in the mouse studies, but appears to be very safe with no apparent toxic side effects.

In the team’s previous study, chitosan/IL-12 eradicated tumors in a mouse model of bladder cancer. In this new study, they used mouse models of colorectal and pancreatic cancer. First, using noninvasive imaging techniques, they showed that after injecting tumors with chitosan/IL-12 the cytokine remained within the tumor microenvironment for nearly a week, but when IL-12 alone was injected it remained there for only a day.

Study co-author Dr. David Zaharoff, now at the University of Arkansas, who initially developed the idea for combining IL-12 with a bioadhesive, likened chitosan to maple syrup. “The high viscosity of chitosan inhibits diffusion of co-formulated molecules,” he said. “As a result, chitosan is able to hold IL-12 in the tumor microenvironment and maintain it there for a long period of time.”

In a second set of experiments, they showed that intratumoral injection of chitosan/IL-12 once a week for 3 weeks completely eradicated tumors in 90 percent of the mice, whereas IL-12 alone had only limited efficacy. There was little impact on tumor shrinkage or survival when chitosan was combined with GM-CSF and IFN-γ, two other proteins that can stimulate the immune system. “This complete tumor regression seems to be unique to chitosan/IL-12,” the researchers wrote.

The treatment triggered the activity of two powerful types of immune cells, CD8+ T cells and natural killer cells. And in certain circumstances, when the researchers “rechallenged” the cured mice with tumor cells, the initial treatment offered lasting immune protection against cancer. But the extent of the protection, they cautioned, was dependent on how many tumor cells were injected into the mice and how often, and must be examined in “a more clinically relevant [animal] model.”

Despite its robust antitumor effects, the toxicities IL-12 induced in the initial human trials drove away industry interest in it, explained Dr. Jeffrey Weber from the H. Lee Moffitt Cancer Center & Research Institute in Tampa, FL. “But I still think that this is a drug that needs to be pursued,” he said.

Even so, Dr. Weber, who was not involved in the study and whose work focuses on vaccines to treat melanoma and other tumors, expressed doubts about the long-term prospects of IL-12 as a stand-alone therapy, arguing that the available evidence suggests it would be best pursued as an adjuvant to boost the performance of therapeutic vaccines. A requirement to inject the treatment directly into the tumor may also “limit its appeal and its indications,” he continued.

The phase I trial, which will be conducted at the NIH Clinical Center in Bethesda, MD, will enroll patients with superficial bladder cancer (cancer limited to the lining of the bladder wall) whose disease has returned after standard first-line therapy. In the case of bladder cancer, Dr. Greiner added, because chitosan/IL-12 appears to generate a strong adaptive immune response—that is, immune cells are spurred to action and develop a “memory” of the pathogens or cells that mandate a similar response in the future—it may also present “an opportunity for evaluating this approach in patients with metastatic lesions who cannot undergo surgical removal of the bladder.”

Similar efforts to target the delivery of IL-12 to tumors, including encapsulating the protein in viruses and liposomes, are being investigated. But combining IL-12 with chitosan may offer several advantages over these other approaches. Chitosan, for example, is already used in humans to promote blood clotting and reduce lipid absorption in the stomach, and it has a proven track record for safety, Dr. Zaharoff stressed, and the once-a-week treatment schedule will limit the type of systemic exposure that can cause toxicities.

In addition, unlike some other approaches to improve IL-12 delivery, preparing the IL-12 and chitosan mixture doesn’t require solvents and other processes that break down the protein, and it can actually be made at the bedside just prior to administration.

“It’s a very simple approach, but it was designed to be that way so it can be moved into human trials in a short period of time,” Dr. Zaharoff said. “As far as translational research goes, you can’t get much more efficient than this.”

Carmen Phillips

Spotlight

NCI’s Cancer Information Service: Providing Information and Assistance Nationwide

Rick Muha had been active his whole life. So when he found his waistline expanding for no apparent reason, he tried to deal with it head on. One night after a long run, he was stretching and felt something strange in his lower back—a hardness that didn’t belong.   

“Sure enough, when I went upstairs I felt an outline of a hard mass,” his wife and NCI employee Cathy Muha said. That night at the after-hours clinic, an x-ray revealed a large tumor attached to his hip.

“From there, my husband’s situation got fast and furious,” she said. “I was left with a feeling of not knowing where to go; not knowing what kind of information I needed to prepare us for what we were about to face. As someone who works for NCI, I knew thousands of Americans confront this same feeling every day. But suddenly I was experiencing the daunting reality first-hand, and I realized how overwhelming it could be.”

This common scenario is why NCI’s Cancer Information Service (CIS) Contact Center exists, said Program Director MaryAnn Monroe. “The Contact Center provides information that is personalized and tailored to meet an individual’s need,” she explained. “There are no scripts and conversations and information provided are completely confidential. Our information specialists take as much time as needed to really help individuals understand their situation.”

Specialists Trained to Help

Lissett Santiago is one of 66 highly trained information specialists with NCI’s Cancer Information Service. Lissett Santiago is one of 66 highly trained information specialists with NCI’s Cancer Information Service.

For 35 years, NCI’s CIS Contact Center has been just a phone call away for anyone with questions about cancer. Since it was established in 1975, the CIS has answered well over 10 million calls. Whether an individual has been diagnosed with cancer or they have a loved one with cancer, the service is available free of charge.

“Cancer touches the lives of so many, and having caring, highly trained, and sensitive cancer information specialists available to answer questions and provide information may be what that person needs to be able to make informed decisions about their care,” said Mary Anne Bright, associate director of NCI’s Office of Public Information and Resource Management.

NCI’s CIS is located at the Fred Hutchinson Cancer Research Center in Seattle, WA, where a staff of 66 information specialists with backgrounds such as nursing and social work respond to thousands of calls, LiveHelp chats, and e-mails each year.

The information specialists who speak with callers undergo 6 weeks of initial training. They learn about cancer and cancer-related topics and how to navigate various online NCI resources to provide callers with the information they need. But, in addition to providing up-to-date information on cancer, Bright explained, sometimes they provide an understanding ear. ”Our information specialists care about more than just the accuracy of their information,” Bright said. “They also care about how they are delivering it, and how their clients feel about the service they receive.” NCI’s CIS, she continued, has the highest customer satisfaction scores in the Federal government to prove it.

Audio Audio Clips of Telephone Calls to NCI’s Cancer Information Service
(Type: MP3 | Time: 3:34 | Size: 41.2 MB)
Read the transcript
Listen to re-enactments of actual calls to the CIS Contact Center. The selected inquiries are followed by responses from CIS information specialists and then closing comments from callers. There is a two second pause between segments.

According to Leah Counts, a 2-year veteran CIS information specialist, for many of the people she talks with, one of the most difficult times comes right after diagnosis. “It’s the first time they’ve been diagnosed with cancer, and having to think about treatment options while dealing with the emotional stress is difficult for people,” she said. “Our service really offers something valuable to people by helping make their situation less overwhelming.”

The CIS Contact Center also provides information about available clinical trials, and that’s something that doctors don’t always talk about, said Deb Pearson, an NCI public health advisor. "Our mission is to support NCI and its research, and cancer treatment trials should be in the conversation from the very beginning, whenever possible,” she said. “Having people participate in these trials helps move research forward,” she stressed, and a clinical trial may be the best treatment option.

One Family’s Journey

As an NCI employee, Muha was familiar with the service before her husband’s diagnosis. But, she admits, “I had some trepidation about calling a 1-800 number when we heard the word ‘cancer’ and were suddenly propelled into a parallel universe.”

Over the course of her husband’s illness, Muha called the CIS Contact Center five times. She said the service was helpful along the entire cancer continuum, from diagnosis information to long-term survivorship issues. “The support we got was credible, confidential, and caring, and the information specialists used the most up-to-date science to help us go through our cancer journey,” she said.

“The most helpful part about calling the CIS was the assistance I got with understanding treatment options,” she continued. “When I went into a doctor’s office, I already knew the kinds of options that were available, the questions to ask, and had the validation that what we decided was the right course of action.”

The Contact Center also helped the couple figure out how to explain the situation to their kids in a way that was suitable to their varied ages. And because the Contact Center is available nationwide, instead of explaining her husband’s situation to relatives across the country, Muha could simply direct them to the CIS Contact Center.

“The consistency, quality of information, and same empathetic ear was really important to me when recommending that people call,” she said.

Multiple Avenues of Assistance

Over the years, the CIS has gone through multiple transformations to become what it is today. Bilingual information specialists who cater to Spanish-speaking callers first joined the CIS over 25 years ago. And the CIS Contact Center now is available to the public for longer hours (8:00 a.m. ET to 8:00 p.m. ET), offering help and information to more people. In addition to calling 1-800-4-CANCER, one can chat online with information specialists using LiveHelp, send a question via e-mail, and even ask questions on NCI’s recently launched Facebook page.

“The Contact Center deals with people holistically,” Pearson said. From the symptoms they may be having, to financial questions, to directing people to information that their health care providers may be too busy to provide.

Muha credits the CIS with helping her family to get through one of their most difficult experiences. “Services like the CIS don’t perform miracles, but they give you information so you can make decisions and tap into valuable resources,” she said. “That’s its beauty.”

—Sarah Curry

Featured Clinical Trial

Cediranib to Treat Alveolar Soft Part Sarcoma

Name of the Trial
Phase II Study of Cediranib (AZD2171) in Patients with Alveolar Soft Part Sarcoma (NCI-09-C-0192). See the protocol summary.

Dr. Shivaani Kummar Dr. Shivaani Kummar

Principal Investigator
Dr. Shivaani Kummar, NCI Center for Cancer Research

Why This Trial Is Important
Alveolar soft part sarcoma (ASPS) is an extremely rare type of soft-tissue sarcoma that typically affects teenagers and young adults. It usually develops in the muscles or deep soft tissue of the legs, but it can also arise in the trunk of the body, the head and neck region, and the arms. ASPS is a slow-growing cancer, and it often does not produce symptoms until it has reached an advanced stage. Consequently, the long-term outlook for patients with this type of cancer is poor.

Surgery is the most effective treatment for ASPS, but many patients have widespread metastatic disease by the time they are diagnosed and are not candidates for surgical treatment. In addition, chemotherapy regimens that have been used to treat other types of soft tissue sarcoma are not effective in patients with ASPS. There is no currently accepted standard of care for advanced ASPS.

Cediranib is an experimental drug that blocks the activity of a number of proteins important to the growth of new blood vessels to tumors, a process known as tumor angiogenesis. Because ASPS tumors are highly angiogenic, doctors want to know if cediranib would be effective in slowing or stopping their growth. In early trials of the drug, patients with ASPS showed some partial responses or disease stabilization. Based on these findings, researchers at NCI are conducting a phase II clinical trial of cediranib in ASPS patients.

In this trial, patients with metastatic ASPS will be treated with cediranib by mouth once a day in 28-day cycles until disease progression or unacceptable toxicity. Doctors will monitor patients for signs of tumor shrinkage and possible side effects of treatment.

“Cediranib is showing preliminary activity in this disease, and, given that no other systemic treatment is effective, I think cediranib presents an option for these patients,” said Dr. Kummar. “In order to evaluate the drug further in this disease, we’ve expanded the trial to enroll more patients.”

Once accepted into the study, patients will visit the NIH Clinical Center every 2 to 4 weeks for examination and to receive the study medication. Travel assistance may be available.

For More Information
See the lists of eligibility criteria and trial contact information or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.

An archive of "Featured Clinical Trial" columns is available at http://www.cancer.gov/clinicaltrials/ft-all-featured-trials.

Cancer Center Profile

The Comprehensive Cancer Center of Wake Forest University

Director: Dr. Frank M. Torti • Medical Center Blvd, Winston-Salem, NC 57157
Phone: 336-716-7971 • Web site: http://www.wfubmc.edu/cancer

Background

Outpatient facility at Wake Forest Comprehensive Cancer Center The outpatient facility at the Comprehensive Cancer Center of Wake Forest University

The Comprehensive Cancer Center of Wake Forest University (CCCWFU) has been an NCI-designated cancer center since 1974 and has been continuously funded by NCI since this designation became available.

The Center was founded with a strong community orientation. It was conceived and developed around a community-wide effort in clinical trials and cancer control research. This region includes substantial numbers of African Americans, Latinos, Native Americans, rural poor, and pockets of urban poverty. Institutional awareness of local history and the importance of the cancer problems in these populations have helped the CCCWFU staff focus on addressing cancer issues that are important to communities in the region.

Research

The CCCWFU has built a team of nationally and internationally recognized experts who are committed to advancing knowledge and improving cancer treatment. At the core of the Center are its faculty and staff, covering nearly every discipline within the Wake Forest University (WFU) Baptist Medical Center, as well as faculty and staff from other campuses, such as those at the WFU graduate schools and affiliate institutions. CCCWFU recognizes the importance of building cross-departmental and interdisciplinary collaborative team approaches to advance the science and treatment of cancer. Such collaborative efforts include research on natural products, cancer genomics, nanotechnology, the tumor microenvironment, novel anticancer drugs, cancer survivorship, and cancer health disparities.

The Center is divided into four programs: Cell Growth and Survival, Cellular Damage and Defense, Clinical Research, and Cancer Prevention and Control. There also exist three Centers of Excellence in brain, breast, and prostate cancers. The Centers of Excellence foster translational research by bridging basic and population sciences with clinical research.  

Patient Care

The CCCWFU is the primary tertiary referral center for a large geographic region that contains approximately 9 million people. The Center provides the region’s underserved populations with cancer prevention and early detection services, as well as access to over 200 clinical trials. The Center emphasizes research that will serve the diverse populations in its region.

The CCCWFU has a state-of-the-art 250,000 square foot outpatient clinic (opened in 2003). In 2011, the Center will break ground on an inpatient cancer facility that will add six floors over the outpatient clinic to create a 520,000-square-foot cancer complex. The anticipated completion date of this project is in 2013.

Other Notable Programs

The CCCWFU also provides patients with an extensive hereditary risk assessment and counseling program. In addition, it is an active partner with Wake Forest’s Maya Angelou Center for Health Equity, founded by the renowned poet, Dr. Maya Angelou, to address health disparities across the surrounding region and the nation. Furthermore, the Center fosters close interactions between its NanoCenter, the Wake Forest Institute of Regenerative Medicine, and a joint program with Virginia Tech in biomedical engineering.

Legislative Update

Project Cancer Education: An Introduction to Translational Research at NCI

Congressional staff members and representatives from cancer advocacy organizations visited Dr. Natasha Caplen’s lab on July 30 as part of an informational program called Project Cancer Education. Congressional staff members and representatives from cancer advocacy organizations visited Dr. Natasha Caplen’s lab on July 30 as part of an informational program called Project Cancer Education.

On July 30, NCI and the Association of American Cancer Institutes (AACI) hosted a pilot program called Project Cancer Education for six Congressional staff members and representatives of cancer research advocacy organizations. The educational program, held on the NIH main campus in Bethesda, MD, was intended to inform attendees about new concepts in cancer research.

After a brief welcome by Susan Erickson, director of NCI’s Office of Government and Congressional Relations, the participants toured the NIH Clinical Center. The tour included a visit to the pediatric unit to get a sense of pediatric patients’ cancer experience and to learn about the work of Dr. Jun Wei, an NCI researcher who studies pediatric neuroblastoma.

In the Clinical Center’s pathology lab, attendees learned about the critical importance of properly storing and handling patient tissue samples for accurate diagnosis and future research use. To give the advocates and Congressional staff a glimpse of the evolving understanding of cancer, each participant received a traditional pathology report similar to those given to newly diagnosed patients, as well as a genotype report that described the actual genetic abnormalities associated with the patient’s tumor. The group then visited Dr. Natasha Caplen’s laboratory to see how genetic information might be used to validate the particular genes that function abnormally in an individual tumor, as well as to learn about Dr. Caplen’s research on gene silencing and observe first-hand the collection and analysis of gene expression array data.

Dr. Ola Landgren talked with attendees about his research on multiple myeloma, including new ways of thinking about precursor diseases to cancer, such as smoldering myeloma. He walked the group through further testing, potential treatments, innovative clinical trials, and the prognosis for a patient with this disease.

Dr. Lee Helman, CCR’s scientific director for clinical research, and Dr. Don Benson, Ohio State University assistant professor and an AACI representative, wrapped up the day’s events with a talk about the importance and power of translational research. Both emphasized the interdependence of research in the lab and in the clinic, and the seamless partnership between NCI and the network of cancer research institutions across the country.

Cancer.gov Update

NCI Recovery Act Web Site Highlights Cancer Disparity Studies

NCI has added a new article to its Recovery Act Web site that highlights how Recovery Act funding is enabling collaboration among researchers from different institutions to conduct genome-wide association studies (GWAS) to better understand why some populations experience disproportionately high rates of certain cancers.

Researchers at institutions such as the University of Southern California, Barbara Ann Karmanos Cancer Institute/Wayne State University, University of Texas M. D. Anderson Cancer Center, and University of California, San Francisco, are conducting studies of African American patients with the goal of uncovering genetic factors that are associated with prostate and lung cancer risks. Researchers hope these findings will ultimately lead to improvements in cancer prevention, screening, and treatment.

Notes

NIH Intramural Research Program Is Recruiting Earl Stadtman Investigators

The NIH Intramural Research Program is seeking candidates to be named Earl Stadtman Investigators. These tenure-track level positions are for creative and independent thinkers eager to take on high-risk research that will have an impact on the understanding of disease and medicine. Some of the areas of active recruitment include sensory biology and the neurosciences, symptoms research, systems biology, cancer, infectious diseases (including HIV and AIDS), and bioinformatics.

The positions are named for Dr. Earl Stadtman, an accomplished biochemist and mentor, who worked at NIH for more than half a century.

Applicants are asked to share their ideas for a novel research program, their career aspirations, and how they would contribute to the NIH mission. Candidates in any area of biomedical, translational, and behavioral research are invited to apply. Applications must be received by October 1.

Learn more about the eligibility criteria and how to apply online.

Office of China Cancer Programs Issues Report on Symposium

Cover of Personalized Medicine: Building on 30 Years of China-U.S. Cooperation

NCI's Office of China Cancer Programs (OCCP) has released a report titled "Personalized Cancer Medicine: Building on 30 Years of China–U.S. Cooperation, Executive Summary." The summary details the proceedings of the 30th Anniversary Symposium, held in Beijing in November 2009 to commemorate 3 decades of a collaborative agreement between the United States and China.

The report also highlights the accomplishments of past and ongoing U.S.–China cancer research studies, summarizes the status of several technologies that are driving the development of personalized cancer medicine, and identifies emerging opportunities for future cooperation in areas including molecular epidemiology, genomics, proteomics, and nanotechnology.

The report is available online. Order copies of this report and other NCI education materials from the NCI Publications Locator Web site or by calling 1-800-4-CANCER.

 

New Issue of OCG e-News Available

The NCI Office of Cancer Genomics (OCG) recently published a new issue of OCG e-News, a free quarterly newsletter to keep members of the cancer community informed about developments in NCI's genomic programs and initiatives. OCG e-News serves as a resource for understanding cancer genomics by providing the latest news on OCG initiatives, updates on developments and innovations in molecular medicine, and perspectives from patient advocates and researchers behind the science. Learn more about this resource online and share your own ideas and input by sending an email to ocg@mail.nih.gov

To sign up to receive OCG e-News, as well as updates from the Office of Cancer Genomics, visit http://ocg.cancer.gov/email_signup.asp.