National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
October 4, 2011 • Volume 8 / Number 19

BREAKING NEWS

Study Estimates Health Risks for Women Exposed to DES In Utero

Up until 1971, doctors in the United States prescribed a drug called diethylstilbestrol (DES) to millions of healthy pregnant women. The daughters of these women, who were exposed to the drug in utero, are at an increased risk of developing a range of adverse health effects related to the exposure. A study in the October 6 New England Journal of Medicine estimates the absolute risks of these health effects and summarizes decades of research on so-called DES daughters. For more information, see NCI's press release.

NEWS

Combination Therapy May Help Some Patients with Advanced Breast Cancer

A combination of two available cancer drugs could offer a new treatment option for postmenopausal women whose advanced breast cancer has stopped responding to hormonal therapy, researchers said last week at a scientific meeting in Stockholm, Sweden. 
Read more > >

 

COMMENTARY

NCI's Office of Advocacy Relations: Bringing Advocacy and Research Together

by Shannon Bell

Just as researchers and clinicians have begun to better understand that cancer is a highly complex group of diseases and have adjusted how they study and treat these diseases, cancer advocates have realized that effective advocacy is a complex and multidimensional pursuit—one in which they can play many roles. Read more > >

A Conversation with Dr. Jane Perlmutter about the Role of Advocates in Cancer Research

A breast cancer survivor and cancer research advocate explains why she turned to advocacy and describes her experience as the lead advocate on one national study. Read more > >

  

IN DEPTH

UPDATES

  • FDA Update

    • Bone Density Drug Approved for Prostate and Breast Cancer Patients
  • NIH Update

    • NIH's Intramural Research Program Unveils New Website
  • Legislative Update

    • Congressional Members and Staff Turn to NCI for Cancer Research Information
    • Congressional Appropriations Committees Put Forward Labor-HHS Bills
  • Cancer.gov Update

    • NCI Updates Online Dietary Recall Tool
  • Notes

    • Rudolf Jaenisch Receives National Medal of Science
    • NCI's James Gulley Wins Presidential Early Career Award for Scientists and Engineers
    • New National Cancer Advisory Board Member Named
    • Cyber-Seminar Will Address Cancer Control and Prevention for Latino Populations
    • Small Businesses: Apply for Cancer Research Funding by November 7


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

Combination Therapy May Help Some Patients with Advanced Breast Cancer

2011 European Multidisciplinary Cancer Congress bannerThe 2011 European Multidisciplinary Cancer Congress meets to showcase the latest European basic, translational, and clinical studies.

A combination of two available cancer drugs could offer a new treatment option for postmenopausal women whose advanced breast cancer has stopped responding to hormonal therapy, researchers said last week at a scientific meeting in Stockholm, Sweden.

The experimental treatment is a combination of everolimus (Afinitor) and exemestane. In a phase III clinical trial, women who received the combination lived for a median of 11 months without the disease progressing, compared with about 4 months for women who received exemestane alone.

"The benefit is quite remarkable," said lead investigator Dr. José Baselga of the Massachusetts General Hospital, who presented the findings at the European Multidisciplinary Cancer Congress. Many patients in the trial had already received multiple therapies, he noted.

In the United States, everolimus is approved for treating advanced kidney cancer and a form of pancreatic cancer. The drug inhibits a protein called mTOR, which participates in a signaling pathway that is highly active in many cancer cells and promotes cell growth and proliferation. Exemestane, an aromatase inhibitor, is used to treat metastatic breast cancer and may be effective when other aromatase inhibitors no longer work.

The combination of these drugs, Dr. Baselga noted at the European meeting, represents a new potential therapeutic option for these women. The study is "probably the most positive trial ever in metastatic estrogen receptor (ER)-positive disease," he said in a video interview

In July, the trial, called BOLERO 2, was stopped after an early interim analysis of the results showed an improvement in progression-free survival for the combination therapy.

"These are impressive results," commented Dr. Jo Anne Zujewski, head of Breast Cancer Therapeutics in NCI's Division of Cancer Treatment and Diagnosis, who was not involved in the research.

Although there are no data on overall survival yet, Dr. Zujewski agreed that the combination therapy is a new potential option for some patients. The side effects were generally manageable, she added.

Dr. José BaselgaDr. José Baselga presents trial results at the 2011 European Multidisciplinary Cancer Congress in Stockholm, Sweden.

The trial included 724 patients from 24 countries. All of the participants had received the aromatase inhibitors letrozole or anastrozole, nearly half had received tamoxifen, and two-thirds had received chemotherapy.

Novartis, the trial's sponsor, plans to seek regulatory approval this year for everolimus in treating ER-positive advanced breast cancer.

"I would be very surprised if this drug were not approved [for the new indication]," said Dr. Ruth O'Regan, director of the Translational Breast Cancer Research Program at Emory University's Winship Cancer Institute, who also had no role in the trial.

She views the combination therapy as a potential alternative to chemotherapy for treating ER-positive advanced breast cancer when hormonal therapies have stopped working.

When resistance to hormonal therapies occurs, Dr. O'Regan explained, additional signaling pathways become activated. Unlike chemotherapy, which targets rapidly dividing cells, mTOR inhibitors are an example of the kind of treatment that may block growth-promoting signaling pathways.

Many lab studies have suggested the promise of this approach. "What's nice about the current study is that we now have confirmation that this strategy works from a study in patients," said Dr. O'Regan, who has led clinical trials of everolimus.

The results add to recent findings on everolimus and breast cancer. Last December at the San Antonio Breast Cancer Symposium, for instance, researchers presented positive results from a trial of everolimus plus tamoxifen for ER-positive, HER2-negative, metastatic disease.

And in 2009, Dr. Baselga and his colleagues reported that the addition of everolimus to letrozole benefited patients with newly diagnosed ER-positive breast cancer as compared with letrozole alone.

The next step is to "digest the data," Dr. Baselga said in Stockholm. "But it would seem to me that mTOR inhibition will play a major role in all disease stages of ER-positive breast cancer."

Edward R. Winstead

Cancer Research Highlights

Rising Oropharyngeal Cancer Rates Linked to HPV Infection

A new study provides evidence that human papillomavirus (HPV) infection may be responsible for the rise in incidence of oropharyngeal squamous cell carcinoma (OPSCC), a type of head and neck cancer. The research suggests that if these trends continue, by 2020 HPV-positive OPSCC will likely surpass cervical cancer as the most common HPV-associated cancer in the United States. The findings were published online October 3 in the Journal of Clinical Oncology.

Originally thought to be a single disease, OPSCC is now recognized as two distinct tumor types: HPV-positive and HPV-negative. HPV-negative tumors are associated with tobacco and alcohol use, older age at diagnosis, and a poorer prognosis, whereas HPV-positive cancers have risk factors related to sexual behavior, are diagnosed in younger people, and tend to have better survival rates.

A previous study by the same authors showed that OPSCC diagnoses had been increasing since the early 1970s, even as rates of other oral cancers dropped. “We expected that the oral cancers would decline in incidence,” explained lead author Dr. Anil Chaturvedi of NCI’s Division of Cancer Epidemiology and Genetics, “because cigarette smoking, which is a strong risk factor for these cancers, has declined in the United States. The increasing incidence of oropharyngeal cancers during the same time suggested that there could be another risk factor. We hypothesized that HPV infection could be leading to the rise in oropharyngeal cancer incidence.”

To evaluate the prevalence of HPV in OPSCC tumors over time, the researchers used tissue samples from three registries in the Surveillance, Epidemiology, and End Results Residual Tissue Repository Program. They used several molecular techniques to detect HPV DNA, viral load, and mRNA in 271 OPSCC tumor samples collected between 1984 and 2004.

The prevalence of HPV in tumor samples (as assessed by HPV DNA) surged from 16.3 percent in the second half of the 1980s to 72.7 percent during the early 2000s, the researchers found. “These increases may reflect changes in sexual behavior, including increases in oral sex,” said senior author Dr. Maura Gillison of the Ohio State University in a news release.

The researchers also discovered that the incidence of HPV-positive OPSCC in the population more than doubled between the late 1980s and early 2000s, while that of HPV-negative cancers fell 50 percent.

Patients with HPV-positive OPSCC were more likely than patients with HPV-negative OPSCC to be younger and male, and they had better long-term survival rates (median survival of 131 months, versus 20 months for HPV-negative cancers), especially if they were treated with radiation therapy. But “not everyone with HPV-associated cancers is cured,” said Dr. Arlene Forastiere of the Johns Hopkins University, “and we are seeking to understand the molecular genetics of that [patient] subset.”

These findings are not likely to result in immediate treatment changes for OPSCC patients, but they can enroll in clinical trials specifically studying HPV-positive OPSCC, noted Dr. Forastiere.

Since the majority of the HPV-positive tumors contained HPV type 16 DNA, vaccination against this type prior to exposure—in men and women—also may be beneficial, as no screening techniques currently exist. But studies are needed to evaluate the efficacy and cost-effectiveness of vaccination, Dr. Chaturvedi added.

Hospitalization Following Prostate Biopsy Common in Older Men

Men 65 years of age or older who underwent a prostate biopsy were more likely to be hospitalized for a serious complication within 30 days than men who did not have the procedure, according to a new study. The rate of infectious complications, in particular, has risen substantially in recent years, researchers from the Johns Hopkins University School of Medicine reported online September 22 in the Journal of Urology.

To conduct the study, Dr. Edward Schaeffer and his colleagues analyzed clinical records from 1991 through 2007 for nearly 17,500 Medicare beneficiaries who had had a prostate biopsy and approximately 135,000 male Medicare beneficiaries who had not had a prostate biopsy. The data came from NCI’s Surveillance, Epidemiology, and End Results database.

Overall, 6.9 percent of men who had a biopsy were hospitalized within 30 days of their first biopsy. By comparison, only 2.9 percent of the men in the control group were hospitalized within 30 days of a randomly selected date. Men who had had a prostate biopsy had a more than 2.5-fold increased risk of hospitalization for a serious bacterial infection and a more than eightfold increased risk of a complication unrelated to a bacterial infection.

Among men who had a biopsy, rates of hospitalization for reasons unrelated to infection remained relatively stable during the study period, Dr. Schaeffer noted, but rates of hospitalization for infection-related complications rose sharply from 2000 to 2007. The finding seems to confirm what urologists around the country have reported anecdotally: A growing number of men are developing antibiotic-resistant infections following a prostate biopsy.

“Two decades ago we didn’t have problems with resistant organisms,” Dr. Schaeffer said. The available evidence suggests that it may be a growing problem, he continued, “and we have to do a better job of controlling it.”

Men about to undergo a prostate biopsy typically receive antibiotics to prevent infections. The Johns Hopkins research team is working with researchers at the Northwestern University Feinberg School of Medicine to investigate whether pre-biopsy testing for antibiotic-resistant bacterial strains can reduce infection rates. They have also launched a study of infection rates in men with low-risk prostate cancer enrolled in the active surveillance program at Johns Hopkins, who undergo periodic prostate biopsies.

More than one million Medicare beneficiaries undergo prostate biopsies annually, in most cases as a result of screening for prostate cancer, the study authors noted. Had similar findings been seen in a randomized clinical trial, they added, 1 of every 24 patients who underwent a prostate biopsy would be hospitalized for a complication within 30 days.

“Although prostate biopsy is often considered a benign procedure,” the researchers wrote, “these findings highlight the importance of individualized assessment of the risk-to-benefit ratio of this potentially risky procedure.” Clinicians should discuss the potential for complications with patients considering prostate biopsy, they concluded.

Study Examines Sex Differences in Screening Colonoscopy Findings

A large study in Austria has shown that the prevalence of abnormal growths detected in screening colonoscopies is higher in men than in women at all ages. The study results, reported September 28 in JAMA, suggest that the optimal age for an initial screening colonoscopy may differ for men and women.

In many countries, including the United States and Austria, guidelines recommend screening for colorectal cancer (CRC) starting at age 50 for men and women of average risk. Colonoscopy is used to find and remove precancerous growths known as polyps or adenomas, especially advanced adenomas (AAs). Colonoscopy also can detect CRC at an earlier stage, when it is generally more treatable.

“This study is important…but it’s not a reason to change screening recommendations in the United States. It’s one report, and the implications for people in the United States aren’t clear,” said Dr. Stephen Taplin, a cancer screening expert and chief of the Process of Care Research Branch in NCI’s Division of Cancer Control and Population Sciences

The study, led by Dr. Monika Ferlitsch of the Medical University of Vienna, analyzed findings from 44,350 participants in a national screening colonoscopy program from 2007 to 2010. Women made up 51 percent of the study population, and the median ages were 60.7 years for women and 60.6 years for men.

Dr. Ferlitsch and her colleagues found that the rates of adenomas, AAs, and CRC detected by colonoscopy were higher in men than in women at all ages, with men having twice the risk of CRC detected by colonoscopy as women. The prevalence of AAs detected was similar between men 45 to 49 years of age and women 55 to 59 years of age. The average number of patients who had to be screened to detect adenomas, AAs, or CRC was significantly higher in women than men.

“There is interest in the wider community of people working on disease screening to think about individualizing recommendations based on more than age,” Dr. Taplin noted. “This study is beginning to push the envelope of research” in that area, he said.

However, Dr. Taplin added, the study findings “need to be replicated in other populations, including those that are more diverse and have different dietary habits than in Austria.” He noted that U.S. SEER cancer statistics show CRC rates only one-third higher in men than women.

Dr. Taplin added that NCI is launching a multicenter research program called PROSPR that will include studies of the benefits and risks of cancer screening in people with different risk profiles in community practice settings in the United States.

Delivering Chemotherapy to the Liver May Benefit Patients with Metastatic Melanoma

For patients with melanoma of the eye (ocular or uveal melanoma) that has spread to the liver, a new technique may delay the progression of the disease better than current treatments, new research suggests. The technique, called percutaneous hepatic perfusion, delivers chemotherapy directly to the liver, sparing other parts of the body from the drug’s effects.

Ocular melanoma frequently spreads to the liver, and because there are no effective treatments, most patients die within several months. 

“This is the first treatment to show a clinical benefit in patients with liver metastases from ocular melanoma,” said Dr. James Pingpank of the University of Pittsburgh Cancer Institute in a news release. He presented results from a study testing the approach—sometimes called regional chemotherapy—last week at the European Multidisciplinary Cancer Congress in Stockholm, Sweden.

In the phase III clinical trial, 93 patients were randomly assigned to receive regional chemotherapy or the best alternative therapy, as chosen by the investigator. The median time before disease progressed in the liver was 8.1 months among those who received regional chemotherapy, compared with 1.6 months for those in the control group.

The study, which began at NCI and was expanded to nine other U.S. medical centers, also showed a benefit in median overall progression-free survival: 6.1 months in the regional chemotherapy group versus 1.6 months in the control group. Most patients retained 80 percent or more of their daily functional status and returned to full performance once therapy was completed, said Dr. Pingpank.

Patients who initially received the best alternative care were allowed to cross over and receive regional chemotherapy if the disease continued to progress. “These patients were able to achieve a benefit from regional chemotherapy even after their earlier treatment,” said Dr. Marybeth Hughes of NCI’s Center for Cancer Research, who co-led the trial.

To deliver the drug, melphalan, doctors use an intra-arterial catheter, inserted through the skin to deliver drugs to the liver, capture the flow of blood from the liver, and then remove the drugs from the blood before it returns to the rest of the body. The technique avoids the complications of major surgery and can be repeated if necessary.

“We see this as a frontline therapy for patients with this disease,” said Dr. Pingpank in the news release. He noted, however, that applying a regional therapy to patients with metastatic disease can be controversial, especially if there is a high risk for metastases elsewhere in the body.

A similar approach could potentially be used for other cancers that have spread to the liver. At the meeting, Dr. Pingpank and his colleagues reported positive results from a phase II study of percutaneous hepatic perfusion for patients with metastatic neuroendocrine tumors.

The device used to deliver and filter the melphalan has been approved in Europe for use in all malignant liver tumors, whereas approval is pending in the United States for melanoma only, the researchers said.

Smoking Cessation Drug Proves Effective in Single-Center Trial

In a single-center randomized controlled trial, the smoking cessation drug cytisine was more effective than a placebo at helping participants abstain from smoking. Results from the trial, conducted at the Maria Sklodowska-Curie Memorial Cancer Center in Warsaw, Poland, appeared in the September 29 issue of the New England Journal of Medicine.

Cytisine binds to the alpha-4 beta-2 nicotinic acetylcholine receptor, which has been implicated in nicotine dependence and is the primary target for the smoking cessation drug varenicline. Cytisine has been available for more than 40 years as a smoking cessation aid in some eastern European countries, although results from animal studies have suggested that cytisine might have limited efficacy in humans.

The research team randomly assigned 740 participants to receive cytisine or a placebo for 25 days. All study participants received a minimal amount of counseling. Twelve months after the end of treatment, 31 participants in the cytisine group and 9 in the placebo group remained smoke-free, an abstinence rate of 8.4 percent versus 2.4 percent. Smoking abstinence was verified by measuring the carbon monoxide concentration in exhaled breath.

Cytisine resulted in more gastrointestinal adverse events than did placebo, but rates of other adverse events and death were similar in the two groups. The rates of discontinuation or dose reduction were also similar with cytisine and placebo.

“Combining cytisine with more intensive behavioral support may result in higher absolute quit rates,” wrote the authors, “and it is possible that efficacy could be improved by a longer regimen.” They also noted that the lower cost of cytisine as compared with that of other smoking-cessation drugs “may make it an attractive treatment option for smokers in low-income and middle-income countries.”

Dr. Michele Bloch, acting branch chief of NCI’s Tobacco Control Research Branch, noted, “The combination of cytisine with behavioral strategies is promising and worthy of further investigation.”

 

Also in the Journals: Zoledronic Acid May Benefit Postmenopausal Women with Breast Cancer

A planned subset analysis of a phase III trial showed that adding zoledronic acid, a bisphosphonate, to standard adjuvant therapy for stage II or III breast cancer may improve outcomes in postmenopausal women. Overall, among the entire trial population of 3,360 women, the addition of zoledronic acid did not improve outcomes. 

However, among a subset of women who had undergone menopause 5 or more years before study entry, the 5-year overall survival rate was 85 percent for those who received zoledronic acid, compared with 79 percent for those treated with standard adjuvant therapy alone.

These findings from the AZURE trial were published online September 25 in the New England Journal of Medicine and presented the same day at the 2011 European Multidisciplinary Cancer Congress. In the full study population, there were 17 confirmed and 9 suspected cases of osteonecrosis of the jaw in the zoledronic acid group and none in the control group.

The benefit in overall survival among postmenopausal women “is a small but significant increase,” said principal investigator Dr. Robert Coleman in a news release. The finding is not conclusive on its own but “in the context of other studies and additional data anticipated later in the year,” he believes it may change practice.

Guest Commentary by Shannon Bell

Advocacy series icon In recognition of the expanding role of cancer advocates, the NCI Cancer Bulletin will publish periodic articles on cancer advocacy, tagged with a purple series icon. To read more articles in the series, click here. Like all content in the NCI Cancer Bulletin, these articles can be republished free of charge and without prior permission.

NCI's Office of Advocacy Relations: 
Bringing Advocacy and Research Together

Shannon BellShannon Bell

Just as researchers and clinicians have begun to better understand that cancer is a highly complex group of diseases and have adjusted how they study and treat these diseases, cancer advocates have realized that effective advocacy is a complex and multidimensional pursuit—one in which they can play many roles.

The mission of NCI's Office of Advocacy Relations (OAR) is to support cancer advocates in their efforts. We do that by identifying and facilitating opportunities for NCI to collaborate with the advocacy community to find more effective ways to advance cancer research and patient outcomes. A key part of our work involves providing advocates with the information, tools, and opportunities they need to bring their experience, expertise, and passion to bear.

The traditional view of cancer advocates—or any disease advocates, for that matter—has been that they support patients and their families and also raise awareness. These roles continue to be vital for the cancer advocacy community.

But over the last decade, cancer advocates have become involved in other substantial ways, such as engaging in the research process and shaping public policies that affect cancer research and treatment. Such activities include serving as members of peer-review panels; forging collaborations with and between researchers; funding research; serving as information gatherers, translators, and disseminators; and communicating with policymakers, researchers, and patient communities.

We in OAR connect advocates with NCI researchers and staff looking to incorporate a collective patient perspective into a broad array of research activities, including the NCI Community Cancer Centers Program and Specialized Programs of Research Excellence, as well as in the design of clinical trials and the review of research proposals.

Just last week, the NCI Director's Consumer Liaison Group (DCLG), an NCI federal advisory committee composed entirely of community stakeholders, met to learn more about and discuss the evolving approach to cancer clinical trials. The meeting allowed DCLG members to get an in-depth look at the clinical trials process. In particular, the group learned from NCI, the Food and Drug Administration, and community researchers about how advances in genomics are leading to novel approaches to clinical trials.

This isn't education for education's sake. Relying on the collective experience of the patients and families on whose behalf they work, DCLG members can use what they have learned to aid in the design or recruitment efforts of novel clinical trials in their own communities.

In OAR, we are evolving to better serve the NCI mission to advance cancer research and improve patient outcomes. This evolution is being driven in part by a report released earlier this year by the NCI Advocates in Research Working Group (ARWG). The ARWG, which was established several years ago under the auspices of the DCLG, was charged with examining NCI's overall efforts to engage the cancer advocacy community and recommending ways to streamline and strengthen these efforts.

The ARWG report includes a number of important recommendations, and OAR is leading the effort at NCI to implement many of them.

One such initiative is aimed at establishing a more robust training program for advocates. Among the first steps is the development of an online repository of training materials produced by NCI, NIH, advocacy organizations, professional societies, and others. The repository will serve as a centralized location for tools and resources that can help advocates understand the research process, understand and translate research findings, and identify ways they can more effectively engage as research advocates. The goal is to have the repository up and running next year.

OAR is in a unique position to act as a convener, identifying areas of alignment within NCI as well as across external stakeholder groups. Recently, OAR collaborated with staff from several NCI offices and numerous disease-specific advocacy organizations to analyze the research that is being conducted across these funding sources. The goal was to identify how these organizations can work together to effectively address gaps in the research and barriers to progress.

Ultimately, our job is to establish relationships and partnerships that advance cancer research and lead to better outcomes for cancer patients, survivors, and their families. More so today than ever, advocates are a critical partner in the cancer research enterprise, and their involvement will become even more imperative in the years to come.

Shannon Bell
Director, NCI Office of Advocacy Relations

Further reading: "Cancer Advocates at ASCO: Connecting for a Cause"

A Conversation With

Advocacy series icon
This article is part of a series of stories related to cancer advocacy. You can read more articles in the series here.

Conversation with Dr. Jane Perlmutter about the Role of Advocates in Cancer Research

Dr. Jane PerlmutterDr. Jane Perlmutter

Dr. Jane Perlmutter is a long-term breast cancer survivor involved in cancer advocacy, specifically cancer research advocacy. She started her career as an experimental cognitive psychologist at the University of Texas in Austin and later worked in a corporate environment. She now runs her own consulting company, Gemini Group. Dr. Perlmutter is a member of several cancer research advisory panels, including the Cancer and Leukemia Group B (CALGB) Breast Cancer Committee, Clinical Trials Transformation Consortium, and Translational Breast Cancer Research Consortium. She is also the lead advocate advisor for NCI's I-SPY2 breast cancer clinical trial.

How and why did you become a cancer advocate?

I was diagnosed with breast cancer 26 years ago. It was very traumatic and, at that time, there was no Internet and very little information available for patients. In the community where I grew up, cancer was still referred to as the "C-word." It was definitely a life-changing event in many ways. I initially thought a cancer diagnosis was a death sentence, although I learned that was not necessarily the case.

Prior to my diagnosis, I was not typically a person who got involved in advocacy work. But I felt I had a responsibility to give back to the community. I got involved doing some peer support through the American Cancer Society's (ACS) Reach to Recovery program. When I moved to Chicago in the early 1990s, I worked with the Y-ME organization and eventually joined the Y-ME board as well.

In the mid- to late-1990s there were more opportunities for cancer patient advocates to become involved in research efforts. Because I was an academic researcher in psychology earlier in my career, that was very interesting to me. One of the first things I did was enroll in the National Breast Cancer Coalition Project LEAD program in basic science, clinical trials, and quality of care, where they train advocates to be more effective in the research environment. Subsequently, I became a grant reviewer for ACS and for the U.S. Department of Defense breast cancer research program.

What do you view as the role of cancer patient advocates in the research arena?

The advocate's primary role is to ensure that medical research focuses on patients' needs and to help researchers be aware of the urgency to change patients' lives for the better as quickly as possible. The more advocates understand and are comfortable with the science, the better we can play that role. 

Our role is not so much to critique the science but to ask the questions—and sometimes they are meant as leading questions: How is this research going to affect patients? How can it affect them faster? If you're designing a clinical trial, have you thought about scheduling things differently to be more convenient for patients? Is your informed consent process really helping patients? Are there ways you can provide other information or do other things to help patients? Asking such questions is one of the most important things for advocates to do.

Is there any specific advocacy experience that you've found especially rewarding?

Perhaps the most rewarding research advocacy experience I have had is as the lead advocate for the I-SPY2 trial, an innovative, biomarker-driven neoadjuvant trial for invasive, nonmetastatic breast cancer patients for whom standard chemotherapy is inadequate. I got involved from the earliest discussions of the trial design and organizational approach, in part because of my special interest in adaptive trial design, and have continued as a member of the I-SPY2 executive committee.

Being the lead advocate provided me with the opportunity to push the envelope in how advocates are engaged. In I-SPY2, I enlisted about 50 advocates who helped ensure that the trial was attractive to potential patients and that patients could easily complete all requirements. These advocates reviewed the protocol and informed consent documents, and developed patient educational material. Also, some advocates have been part of many of the scientific working groups and other committees and/or engaged with specific trial sites. We have also established a partnership with Y-ME for patients who are interested in receiving peer support from specially trained peer counselors.

I expect the I-SPY2 trial to advance the way investigational drugs are tested, including the more extensive involvement of patient advocates in the research process.

What is your advice to new or future patient advocates who want to maximize their impact on research?

My advice is, first, let other people and organizations know of your interest and expertise. You may really want to be on an advisory board like the NCI Director's Consumer Liaison Group (DCLG), but that's not going to happen right away. Prove your merit by getting involved locally. Get to know and understand the science as well as the culture of research.

There is very little room, in my opinion, for advocates who just sit and listen all the time. You have to speak up, or you're not going to add anything. However, when you first join in the research community, it is very good to sit back, listen a lot, see how the dialogue goes, and learn how to formulate your questions. I also urge new advocates to get a really great mentor from the advocacy community.

The environment for advocates is really changing. I personally love research advocacy because I love the research process, but everyone has to find his or her own niche. There's a lot of good work to be done in peer support and public education, and in lobbying legislators for more research funding. There's also a lot of overlap among advocates' various roles. I still do peer-to-peer support with cancer patients. 

In some ways, we've learned so much about cancer since I was first diagnosed. But in other ways, we've made so little progress. What we really have to do is push the envelope, change the paradigm, and work smarter.

Special Report

Workshop Examines Causes, Potential Remedies for Drug Shortages

Worsening shortages of many drugs are increasingly affecting patient care, according to numerous participants at a Food and Drug Administration (FDA)-sponsored workshop held last week. Drugs in short supply include antibiotics, anesthesia drugs, and intravenous nutrition. Cancer drugs, however, make up the largest proportion of drugs in short supply, and the impact of the shortages on cancer care was a focus of discussion at the daylong meeting.

 When effective chemotherapy drugs have been unavailable, oncologists have had to turn to alternative drugs that may be less effective and are often more toxic.

The workshop came only days after Department of Health and Human Services Assistant Secretary for Health Dr. Howard Koh told attendees of a congressional hearing that shortages of cancer drugs—primarily of older chemotherapy agents that are the backbone of treatments for a number of cancers—have delayed or halted enrollment in many NCI-sponsored clinical trials.

The September 26 workshop brought together key stakeholders—including physician and hospital group representatives, patient advocates, and drug industry representatives—in an effort to better understand the reason for the shortages and to discuss potential solutions to what have been the largest and, for some of these drugs, the longest-lasting shortages on record.

Although numerous participants reported that the shortages are affecting growing numbers of patients, the FDA also had some good news to report. Working closely with drug manufacturers, the agency said, it has been able to prevent 99 new shortages this year.

The Cancer Impact

Drug shortages began occurring regularly more than a decade ago, but they have worsened in recent years. According to the FDA, the number of drugs in short supply has tripled since 2005. In 2010, 178 drugs were in short supply, said Dr. Edward Cox, coordinator of FDA’s Drug Shortage Program. And, he continued, 2011 “is expected to be worse.”

The chemotherapy drugs currently in short supply include decades-old drugs such as 5-FU, vincristine, daunorubicin, cytarabine, and leucovorin, which have long been part of standard treatments for leukemia and for testicular and colorectal cancers. Almost all of the drugs are sterile injectables and available as generics. In fact, in many cases, the brand-name versions of the drugs are no longer manufactured, said Dr. Ralph Neas, president of the Generic Pharmaceutical Association.

When effective chemotherapy drugs have been unavailable, oncologists have had to turn to alternatives that may be less effective and are often more toxic, said Dr. Lawrence Solberg of the Mayo Clinic Jacksonville. As a result, he continued, patients “are experiencing increased suffering.”

Diane Hamlin and her 16-year-old daughter, Abagale, put a human face on just what the shortage can mean for some patients. Abagale was diagnosed with acute myeloid leukemia in March 2011. One of the drugs that is highly effective against AML, daunorubicin, was not available. So Abagale’s physicians had to use doxorubicin instead. (Doxorubicin, however, is also in short supply.)

The mucositis in her mouth, throat, and stomach caused by the drug was so severe that Abagale was in constant pain, had to receive heavy doses of painkillers, and had to be fed through an IV tube. The ordeal, which lasted nearly a month, “was a very dark time for me,” Abagale said.

Causes and Side Effects

Economic forces and regulatory and manufacturing problems, among other issues, have all contributed to the shortages, said Dr. Douglas Throckmorton, deputy director of FDA’s Center for Drug Evaluation and Research. The largest contributor—accounting for roughly 54 percent of the shortfall—has been product quality and manufacturing issues, such as failure to comply with good manufacturing practices and issues with particulate matter in drug vials.

Other key factors have been product discontinuations, industry consolidation (just seven companies now produce most of the sterile injectables that are in short supply), and a lack of alternate sources of raw materials used to make the drugs and in manufacturing capacity.

For example, Johnson & Johnson reported September 23 on its website that supplies of Doxil, a form of doxorubicin encapsulated in a liposome, or lipid shell, would be limited over the next few months because the company is transitioning to a new contract manufacturer after its current manufacturer “indicated its intentions to transition out of the contract manufacturing services business over the next several years.”

At the workshop last week, Dr. Neas and other manufacturing representatives disputed whether consolidation in the drug manufacturing industry has had an appreciable impact on the shortages. Jonathan Kafer of Teva Pharmaceuticals, one of the largest manufacturers of sterile injectable drugs, noted that the spike in shortages over the past 2 years has coincided with manufacturing issues at several different companies.

And even after manufacturing problems have been addressed, the product is not immediately available, Kafer stressed. Sterile injectables, which are complex to manufacture, can take several months to become broadly available after production resumes, he said.

There's no one solution that can fix this problem. It's too complex.

—Dr. Erin Fox

A particularly troubling outcome of the shortages, numerous participants said, has been the growth of so-called gray markets: secondary distributors of drugs that are not part of the mainstream distribution process. The safety and reliability of drugs obtained from these distributors is questionable, several participants cautioned, and such distributors often charge outrageous markups.

Bryant Mangum of Premier healthcare alliance reported that in a survey of 42 of Premier’s acute-care hospitals, 18 gray-market vendors made nearly 1,750 offers of back-ordered or unavailable drugs. The average markup for the drugs was 650 percent; the highest markup (for a blood pressure drug) was 4,533 percent, with markups for cytarabine (3,980 percent) and leucovorin (3,170 percent) not far behind.

FDA staff and other participants cautioned hospitals and community physicians not to purchase drugs from gray-market distributors and to report suspect distributors to their state pharmacy boards, to FDA’s MedWatch program, and to state and local authorities.

Searching for Solutions

Following a November 2010 summit on the drug shortages, a stakeholder working group was convened to develop recommendations on how to address current shortages and how to prevent or mitigate future shortages.

Included among the working group’s recommendations was more robust and earlier communication among FDA, industry, hospitals, and clinicians about potential shortages. The group also recommended establishing criteria for identifying drugs that are vulnerable to shortages and processes for ensuring that alternate sources of supply are in place for such drugs. Other recommendations raised at last week’s meeting included the creation of a national stockpile of critical drugs, similar to a system used by the Centers for Disease Control and Prevention for pediatric vaccines.

Many participants praised FDA for its work in averting nearly 100 drug shortages this year alone. The manufacturers played a big role in the process, said Capt. Valerie Jensen, associate director of the FDA’s Drug Shortage Program, by giving the agency early warning of production issues and requesting expedited regulatory review when it was needed to ensure an adequate supply of a critical drug.

Early notification of production interruptions or product discontinuations would be required under the Preserving Access to Life-Saving Medications Act, a bill that has been introduced in the House and Senate, said Joseph Hill of the American Society of Health-System Pharmacists.

Alleviating the shortages will take collaboration and changes in numerous areas, said Dr. Erin Fox of the University of Utah’s Drug Information Service. “There’s no one solution that can fix this problem,” she said. “It’s too complex.”

Carmen Phillips

Further reading: “Continued Shortage of Chemotherapy Drugs Causing Concern


A Closer Look

Changing Face of Cancer in HIV-Positive Patients Requires New Approaches to Clinical Trials

HIV virus emerging from a human immune cell (Image by C. Goldsmith, CDC) The HIV virus (green) buds from a human immune cell (Image by C. Goldsmith, CDC)

In the mid-1990s, the widespread introduction of modern antiretroviral therapies changed a diagnosis of human immunodeficiency virus (HIV) infection from a rapid death sentence to a chronic condition that could be managed over decades. But as the first generation of patients receiving these therapies enters late middle age, new challenges are appearing, including a dramatic increase in the incidence of cancers that were not traditionally viewed as acquired immunodeficiency syndrome (AIDS)-associated malignancies.

Several types of cancer were seen frequently in the early years of the AIDS epidemic; three types—Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer—are called the "AIDS-defining cancers." A diagnosis of one of these three cancers can mark the point where HIV infection has progressed to full-blown AIDS.

Researchers tracking the relationship between HIV and cancer over the decades have noticed a substantial shift in cancer epidemiology in HIV/AIDS patients. In April of this year, investigators from NCI's Division of Cancer Epidemiology and Genetics (DCEG) reported in the Journal of the National Cancer Institute that from 1991 to 2005, even with a quadrupling of the HIV-positive population in the United States, the number of AIDS-defining cancers diagnosed in that population had fallen by more than two-thirds.

In contrast, the number of non-AIDS-defining cancers had tripled, with the highest number of these new cases coming from anal, liver, prostate, and lung cancers and Hodgkin lymphoma. "A big part of it is that patients with HIV are getting older, and many types of cancer just become more common as people age," said Dr. Eric Engels, senior author of the DCEG study.

"The HIV-positive population also has a lot of other risk factors for cancer, and that's also contributing," he added. These risk factors include co-infection with other cancer-causing viruses such as the human papillomavirus (HPV, which causes cervical, anal, oropharyngeal, and other cancers) and the hepatitis C virus (HCV, which causes liver cancer), a high rate of smoking, and possibly the long-term effects of HIV itself on the immune system.

Clinical Trials Conundrum

The increase in HIV-positive patients requiring treatment for non-AIDS-defining malignancies presents a new conundrum: how to provide the best and safest treatments when data from clinical trials are lacking for these patients. "Traditionally, HIV-positive patients were de facto excluded from NCI-sponsored clinical trials, except those targeted to AIDS-defining malignancies like Kaposi sarcoma," said Dr. Robert Yarchoan, director of NCI's Office of HIV and AIDS Malignancy (OHAM).

This exclusion was not based on discrimination, but rather reflected AIDS patients' high susceptibility to drug toxicity, resulting from their profound immunodeficiency. Also, because they were at risk of death from AIDS, they would confound survival results, Dr. Yarchoan explained.

These concerns are now being reevaluated. The development of highly active antiretroviral therapy (HAART, also known as combination antiretroviral therapy) has converted HIV infection to a chronic, manageable disease in most cases, and such patients can now better tolerate chemotherapy. However, a lingering concern is the potential for unknown pharmacokinetic interactions between the antiviral treatments used to keep HIV under control and cancer chemotherapy drugs or newer biological therapies.

Five years ago, to address the changing pattern of cancers in HIV-infected patients, the NCI-sponsored AIDS Malignancy Consortium (AMC, which spun off from the National Institute of Allergy and Infectious Diseases' AIDS Clinical Trials Group in 1995) created a new working group on non-AIDS-defining cancers. "We felt [cancer] was becoming a bigger part of the AIDS epidemic, and we needed to have a way of testing new drugs in these cancers," said Dr. Ronald Mitsuyasu, director of the AMC and the Center for Clinical AIDS Research and Education at the University of California, Los Angeles.

The consortium has finished its first safety trial, looking at sunitinib in HIV-positive patients whose cancers have not responded to standard treatments. It has other such trials in development, testing a variety of newer treatments including vorinostat, erlotinib, and other targeted drugs. "Once we've defined that we can safely give a drug and how to give it, any NCI-sponsored trials of these drugs that excludes patients with HIV will be amended to allow individuals with HIV to enroll, assuming there's no other medical reason they shouldn't participate," explained Dr. Richard Little, who leads HIV research in NCI's Cancer Therapy Evaluation Program (CTEP).

"We're trying to make physicians more comfortable with enrolling HIV patients in general oncology trials, so that [HIV status] won't be an automatic exclusion in the future," said Dr. Mitsuyasu. "Patients with HIV need access to these trials just as much as anyone else does."

Once we've defined that we can safely give a drug and how to give it, any NCI-sponsored trials of these drugs that exclude patients with HIV will be amended to allow individuals with HIV to enroll, assuming there's no other medical reason they shouldn't participate.

—Dr. Richard Little

In a related effort, CTEP has funded the Blood and Marrow Transplant Clinical Trials Network to perform two clinical trials in HIV-positive patients, one of autologous bone marrow transplantation, and one of allogeneic transplantation. "Assuming that these studies indicate that it is feasible and safe to transplant HIV-positive patients for their underlying cancer, trials that currently exclude them based on concerns that this is not safe would be amended," explained Dr. Little.

"I think the culture is actually changing as people are thinking more appropriately about why patients with HIV should be included or excluded," he continued. "We're trying to create a culture where the first idea is, yes, they should be included on a trial unless there's a specific reason that would make that unsafe. People in the research community are being very responsive to that way of approaching patients."

Increasing Visibility

In the early days of the AIDS epidemic, patients with HIV changed the clinical trials process in the United States, demanding rapid access to investigational drugs and encouraging community participation. Today, "people don't volunteer like they used to," said Dr. James Weihe, a psychiatrist who worked on the first AIDS unit at San Francisco General Hospital back in the early 1980s and now works as an advocate and community representative for the AMC.

"You saw all your friends dying around you, so people were motivated" to participate in clinical trials, he remembered. "In 1988, you walked down the street in San Francisco and you saw people with Kaposi sarcoma, you saw young people using canes and walkers and wheelchairs. You don't see that anymore—people look healthy, and the disease has become more invisible."

In addition, even though non-AIDS-defining cancers are becoming more common in people with HIV, "cancer is still relatively rare—people don't know about [the risk], and they don't necessarily talk to each other about cancer, like they would for antiviral trials," he continued.

Since most people are referred to cancer clinical trials by their doctors, Dr. Weihe believes it is important to raise awareness among doctors about cancer trials for HIV-positive patients. "A lot of people don't even know the AMC exists," and outside big cities and academic centers, "a lot of doctors aren't going to have a large HIV caseload. It's especially important for us to work with community physicians, because that's where most patients are going."

Drs. Weihe and Mitsuyasu are excited about a new cancer prevention trial the AMC hopes to launch, which will look at whether anoscopy (an examination of the anal canal) and removal of abnormal tissue can prevent progression to anal cancer, similar to how the Pap smear and treatment of early cervical lesions can prevent the development of cervical cancer. (Both of those cancers are caused by HPV.) "I think the community might get more involved in this sort of trial—trying to prevent cancer," said Dr. Weihe.

The shift from people with HIV getting cancers at an early age to them getting other cancers at a later age is evidence of the public health benefit of better treatments for HIV, concluded Dr. Yarchoan. "Instead of people dying of lymphoma (or AIDS) at the age of 30, they might possibly get lung cancer at the age of 55 or 60. They have many more years without cancer, if they develop it at all. That's a real development that sometimes gets lost in the story," he said.

Sharon Reynolds

Featured Clinical Trial

Testing Adjuvant Ipilimumab in Advanced Melanoma

Name of the Trial
Phase III Randomized Study of Adjuvant Ipilimumab versus High-Dose Recombinant Interferon Alfa-2b in Patients with High-Risk Stage IIIB, IIIC, or IV (M1a, M1b) Melanoma (ECOG-E1609). See the protocol summary.

Dr. Ahmad TarhiniDr. Ahmad Tarhini

Principal Investigator
Dr. Ahmad Tarhini, Eastern Cooperative Oncology Group

Why This Trial Is Important
Melanoma, the most deadly form of skin cancer, begins in melanocytes, which are cells that produce a dark pigment known as melanin. In its early stages, melanoma can often be cured by surgery alone. However, in patients with more advanced disease, even after full resection, relapses occur frequently and few systemic therapies have demonstrated any benefit in terms of delaying recurrences or prolonging life.

Nevertheless, there has been progress in treating patients with advanced melanoma. Recent reports of phase III clinical trials of new treatments have demonstrated that some of them can help improve the survival of patients with inoperable, metastatic disease. One of these new treatments, an antibody called ipilimumab, was shown to extend overall survival by more than 3 months compared to treatment with an experimental vaccine.

Ipilimumab is a type of cancer immunotherapy, meaning it helps a patient's immune system attack tumor cells. Preclinical, clinical, and observational research has shown that the immune system can mount a powerful response against melanoma tumors, including completely eradicating tumors in some patients. For the immune system to mount an effective antitumor response, however, it must be stimulated to recognize and attack melanoma cells. Unfortunately, activation of an antigen called CTLA-4 on cytotoxic T lymphocytes, the very cells known to kill melanoma cells, suppresses the stimulation of these killer cells, effectively putting the brakes on antitumor immune responses. Normally, activation of CTLA-4 is beneficial. It helps control the intensity and duration of immune responses and reduces the chance that immune cells will attack normal tissues. In terms of fighting cancer, however, activation of CTLA-4 is not helpful, so ipilumumab was designed to bind to this antigen and prevent it from suppressing the immune system's ability to attack tumors.

Now doctors want to know if ipilimumab treatment following surgical removal of advanced melanoma tumors will help improve patient outcomes. 

In this clinical trial, patients with stage III or stage IV melanoma that has been completely resected will be randomly assigned to receive adjuvant (post-surgical) treatment with either ipilimumab or high-dose interferon alfa-2b, the current standard of care for patients with resected stage III or IV melanoma. (Eligible patients will have been diagnosed with stage IIIB, IIIC, IV M1a, or IV M1b disease and will have had complete resection of all tumors within the previous 12 weeks.)

"We know that patient immunity is relevant to disease outcome in patients with melanoma. Spontaneous tumor regression has been reported in melanoma, suggesting a role for host immunity, indirectly supported by the presence of lymphoid infiltrates in primary melanoma tumors associated with tumor regression," said Dr. Tarhini. "T-cell infiltrates in the original primary tumor are prognostic of disease outcome, and T-cell infiltrates within regional lymph node metastases from melanoma predict benefit from interferon alfa-2b therapy. In addition, the quality of the patient's immune response seems to differ between earlier and more advanced disease settings, suggesting that these patients are more likely to benefit from immunotherapy in earlier, operable disease stages."

"What these [immunotherapy] drugs do is stimulate the immune system by stimulating an antitumor immune response, breaking the immune system's tolerance of the tumor, or releasing the brake on existing activated antitumor T cells, allowing them to have prolonged activation and increased proliferation," Dr. Tarhini added.

Doctors will determine whether adjuvant ipilimumab improves recurrence-free survival and overall survival compared to adjuvant therapy with high-dose interferon alfa. They will also compare the tolerability of the drugs as well as the quality of life of patients in each arm of the study and will attempt to identify other markers that may predict benefit from ipilimumab treatment.

For More Information

See the lists of entry criteria and trial contact information or call the NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.

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

Community Update


This article is part of a series of stories related to cancer advocacy. You can read more articles in the series here.

NCI Director's Consumer Liaison Group Focuses on Improving Clinical Trials

The NCI Director's Consumer Liaison Group (DCLG), a federal advisory committee made up of advocate leaders who assist NCI in identifying nonscientific barriers to research and provide insight and advice on opportunities to collaborate and communicate with stakeholders, met September 21–23 in Washington, DC. The purpose of the meeting was to hear and discuss advocates' roles in NCI's efforts to modernize and improve the clinical trials process.

The 16-member DCLG, which is overseen by NCI's Office of Advocacy Relations (OAR), heard presentations from researchers at NCI and elsewhere about how scientific advances in understanding cancer are changing the way clinical research is conducted. Topics included discoveries in genomics and immunology, new imaging technologies, development of drugs that target tumor pathways, co-development of targeted diagnostics and therapeutics, adaptive clinical trial design, and phase 0 trials.

Designing More Effective Clinical Trials

How a trial is designed can sometimes determine the success of the treatment being tested. By using discoveries from cancer genomics and cell metabolomics (the study of cellular chemical processes) to identify the subsets of patients who respond well to a novel therapy in phase II trials, and designing subsequent phase III trials to treat patients with similar genetic and metabolic profiles, results can become evident that would have been hidden in a broader population. This targeted approach allows smaller, more cost-efficient phase III trials that are more likely to show a benefit of a drug that is effective for a subset of patients with a particular molecular profile.  

But there are barriers to using this approach, such as explaining this type of trial to newly diagnosed patients and recruiting the large number of potential trial participants necessary to find such specific patient subsets. DCLG Chair Gwen Darien, executive director of Survivor and Patient Advocacy Programs at the Samuel Waxman Cancer Research Foundation, led a group discussion about ways that the advocacy community can influence these and other critical issues to support improvements for more effective clinical trials.

Educating Institutional Review Boards

Another key challenge, highlighted by Dr. Lee Helman, director of clinical science at NCI's Center for Cancer Research, is the need to educate Institutional Review Boards (IRBs). IRBs, which are responsible for approving clinical trial designs at their institutions and medical centers, may not be up to date on the changing requirements for such research studies, he said, particularly the critical need to collect biospecimens from patients to identify genetic and other molecular data key to assessing a targeted cancer drug's effects.

"There is a need for advocates to contact and even serve on an IRB to educate its members from a patient's perspective on the relative risks and benefits" of new clinical trial technologies, suggested OAR Director Shannon Bell. DCLG member Cheryl Jernigan, an advocate and volunteer with Susan G. Komen for the Cure, suggested that advocates identify the national professional organizations that train and accredit IRB participants. Those organizations could partner with the advocacy community to educate IRB members about requirements for modern clinical trial design for cancer drugs.

DCLG members identified other key advocacy issues for clinical trials, including supporting insurance reimbursement for molecular screening of patients in research studies, educating providers and patients about the importance of genomics and biomarker data to determine who will benefit from targeted cancer drugs, and the need for researchers to address the growing problem of cancer patients with other health problems, such as obesity, which disqualify many patients from participating in clinical trials.

Bill Robinson

FDA Update

Bone Density Drug Approved for Prostate and Breast Cancer Patients

The Food and Drug Administration (FDA) has approved the use of denosumab (Prolia, Xgeva) to increase bone mass in two groups of patients at high risk for fractures: men receiving androgen deprivation therapy for nonmetastatic prostate cancer and women receiving an aromatase inhibitor as post-surgical or adjuvant therapy for breast cancer.
  
Denosumab is a monoclonal antibody that binds to and interferes with RANKL, a protein involved in the formation, function, and survival of the cells responsible for bone resorption.

The approvals were based on results from two international randomized double-blind placebo-controlled trials. 

The Hormone Ablation Bone Loss (HALT) trial included nearly 1,500 men with nonmetastatic prostate cancer who were undergoing androgen deprivation therapy. Denosumab was also tested in a 2-year trial that enrolled 252 postmenopausal women with hormone receptor-positive breast cancer who had been treated with an adjuvant aromatase inhibitor.

Both trials showed that one 60 mg injection of denosumab every 6 months increased bone mineral density compared with placebo. In men with prostate cancer, denosumab also reduced the incidence of vertebral fractures and increased bone density in other areas, including the neck and hip. Joint and back pain were the most frequently reported adverse reactions reported by patients treated with denosumab. 

The FDA previously approved denosumab for the treatment of osteoporosis in postmenopausal women at high risk for fracture, as well as for the prevention of skeletal-related events in patients with bone metastases from solid tumors. 

NIH Update

NIH Intramural Research Program Unveils New Website

Screenshot of NIH's Intramural Research Program website

The NIH Intramural Research Program (IRP) recently launched a new website. For the first time, the IRP has a unified website that relays its broad scope and presence on the global biomedical and behavioral research scene.

The new site complements NIH efforts to reach a broad audience that includes scientists outside NIH. The site organizes IRP research by focus area, such as cell biology, immunology, and clinical research. The Research in Action section highlights a few NIH labs and researchers and will be updated regularly with new features. Recent news releases and a sampling of peer-reviewed articles appear in a section called In the News, while the Careers and Research Training sections describe employment and training opportunities at NIH. The NIH Catalyst, the IRP's newsletter, is also featured on the new site.

The site provides a mix of original content along with links to articles and videos from NIH's institutes and centers. Eventually, it will expand to include, among other elements, a page for each principal investigator.

Legislative Update

Congressional Members and Staff Turn to NCI for Cancer Research Information

Molly Daniels of the American Cancer Society; Merria Woods, kidney cancer survivor; and NCI's Drs. W. Marston Linehan and Lee Helman. (Photo courtesy of ACS CAN)From left to right: Molly Daniels of the American Cancer Society; Merria Woods, kidney cancer survivor; and NCI's Drs. W. Marston Linehan and Lee Helman. (Photo courtesy of ACS CAN)

When Congress returned from its August recess, members of both chambers reached out to NCI to learn more about cancer research in a flurry of events and visits.

The rush began with a September 15 congressional briefing on ovarian cancer. Dr. Jennifer Loud of NCI's Division of Cancer Epidemiology and Genetics was invited by the Ovarian Cancer National Alliance to address a gathering of female House members. Representatives Lois Capps (D-CA), Rosa DeLauro (D-CT), and Debbie Wasserman Schultz (D-FL) participated, along with staff from other members' offices. They joined Dr. Loud and researchers from the Department of Defense in a roundtable discussion on advances in ovarian cancer diagnosis and treatment, as well as on the importance of access to appropriate and adequate care.

Staffers for Representative Chris Van Hollen (D-MD) and Senator Ben Cardin (D-MD) attended a September 19 event at the NIH Clinical Center hosted by the American Cancer Society's Cancer Action Network (ACS CAN) to celebrate patients and progress in cancer research. NCI's Drs. Lee Helman and W. Marston Linehan, as well as Merria Woods, a patient of Dr. Linehan's, were featured speakers. Woods talked about her experiences and those of her family when they participated in familial kidney cancer clinical studies at NCI's Center for Cancer Research (CCR). She described how they and others continue to benefit from patient participation in research.

Later that week, on September 22, NCI Director Dr. Harold Varmus met with members of the House Republican Study Committee and their staff to address questions from Congressmen Brian Bilbray (R-CA) and Michael McCaul (R-TX) about cancer clinical trial design and pediatric cancer research. The briefing was organized by the American Association for Cancer Research and coincided with the release of its Cancer Progress Report 2011.

A few blocks away, at the U.S. Capitol Visitor Center, Drs. Kathy Cronin and Angela Mariotto, of NCI's Surveillance Research Program, gave a presentation at the 7th Annual African American Prostate Cancer Disparity Summit, hosted by the Prostate Health Education Network and the Congressional Black Caucus. Drs. Cronin and Mariotto provided an overview of NCI's surveillance research to help participants understand prostate cancer statistics, particularly data on disparities in incidence and mortality between white and black populations in the United States.

Senator Jerry Moran looks through a microscope in Dr. Lee Helman's lab. Sen. Moran is accompanied by NCI's Dr. Patrick Grohar. Senator Jerry Moran looks through a microscope in Dr. Lee Helman's lab, pictured with NCI's Dr. Patrick Grohar. (Photo courtesy of the Office of Senator Jerry Moran)

The same morning, Senator Jerry Moran (R-KS) and two members of his staff visited the NIH Clinical Center to learn more about current NCI intramural research and the unique research opportunities and capabilities afforded by the Clinical Center facility. Drs. Helman and Linehan led Senator Moran and his staff on a tour of the Clinical Center, pointing out how the close proximity of the clinic and laboratory spaces promotes the collaborative process necessary for translating laboratory discoveries into tangible benefits for patients. The senator and his staff talked with a young osteosarcoma patient who is participating in an immunotherapy protocol—an example of the kind of cutting-edge treatment that is possible at the NIH Clinical Center

Dr. Linehan hosted another group last week, as 20 congressional staffers and 11 advocates visited the NIH Clinical Center on September 27. The group met with Dr. Linehan in his lab as part of an event coordinated by the research advocacy organization Research!America. NIH's Office of Legislative Policy and Analysis organized two parallel tours of the NIH Clinical Center that included a welcome from NIH Director Dr. Francis Collins, stops at labs at the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Allergy and Infectious Diseases, and a meeting with a senior investigator in the National Heart, Lung, and Blood Institute's Hematology Branch.

Congressional Appropriations Committees Put Forward Labor-HHS Bills

September also brought appropriations activity in Congress. The Senate Subcommittee on Labor, Health and Human Services, Education, and Related Agencies (Labor-HHS) marked up its appropriations bill, which includes the appropriations level for NIH, on September 20. The full Appropriations Committee voted the bill out of committee on September 21. The Senate bill proposes a $190 million (0.6 percent) reduction to the NIH budget from FY2011 levels, including a reduction of approximately $57 million (1.1 percent) for NCI from FY2011 levels. The full Senate has not yet voted on the bill.

The House Appropriations Committee released its draft FY2012 Labor-HHS bill on September 29, posting the bill and summary tables on its website. The proposal would eliminate funding for the Patient Protection and Affordable Care Act (Public Law 111-148) and proposes $31.7 billion in program funding for NIH, which is $1 billion (3.3 percent) over FY2011 levels and approximately the same as the president's budget request. The proposal includes roughly $5.2 billion in program funding for NCI, also the same as the president's budget request, which represents an increase of about $138 million (2.7 percent) over FY2011 levels. No plans for consideration of the bill have been announced.

For more information on NCI appropriations, cancer specific legislation, recently enacted public laws, and other legislative resources, visit the NCI Office of Government and Congressional Relations website.

Stacye Bruckbauer and Holly Gibbons

Cancer.gov Update

NCI Updates Online Dietary Recall Tool

Screenshot of the ASA24 Automated Self-Administered 24-Hour Recall Website

NCI recently released an updated version of the Automated Self-Administered 24-Hour Dietary Recall (ASA24) system, a web-based software tool to help participants in dietary studies more accurately record their food intake.

ASA24 consists of a respondent website used by participants to enter what they consumed and a researcher website used by investigators to manage study logistics and obtain data analyses. Detailed information about ASA24, including information on registering a study and a demo of the updated respondent website, is available online.

ASA24 was developed by NCI and Westat for researchers who do epidemiologic, intervention, behavioral, or clinical research. Clinicians may also find it useful for diet assessment and nutrition counseling, and educators may find it to be a useful teaching tool.

Notes

Rudolf Jaenisch Receives National Medal of Science

Dr.Rudolf JaenischDr.Rudolf Jaenisch

Dr. Rudolf Jaenisch, a founding member of the Whitehead Institute for Biomedical Research, was named one of seven recipients of the 2011 National Medal of Science by President Barack Obama on September 27.

According to a White House statement, Dr. Jaenisch was lauded for "improving our understanding of epigenetic regulation of gene expression: the biological mechanisms that affect how genetic information is variably expressed. His work has led to major advances in our understanding of mammalian cloning and embryonic stem cells."

Supported in part by funding from NCI, Dr. Jaenisch's research has helped shape the understanding of embryonic stem cells and of induced pluripotent stem cells, which will allow scientists to study complex human diseases, including cancer. These cells may eventually be used in regenerative medicine, potentially supporting the growth of healthy cells and tissues derived from a patient's own cells.

The National Medal of Science is the nation's highest honor for U.S. scientists and engineers. The award is presented annually by the president of the United States to individuals deserving special recognition for outstanding contributions to knowledge or for the total impact of their work on the current state of the chemical, physical, biological, social, or behavioral sciences; mathematics; or engineering. 

NCI's James Gulley Wins Presidential Early Career Award

Dr. James GulleyDr. James Gulley

Dr. James Gulley, deputy laboratory chief and head of the clinical trials group in NCI's Laboratory of Tumor Immunology and Biology, has won a Presidential Early Career Award for Scientists and Engineers. Dr. Gulley won the award for using randomized, controlled studies to test novel recombinant vaccines to reduce the progression of prostate and other cancers and increase patient survival.

The award, the highest honor the U.S. government bestows on scientists and engineers early in their careers, is given annually to scientists and engineers whose early accomplishments show the greatest promise for assuring America's preeminence in science and engineering.

"It is inspiring to see the innovative work being done by these scientists and engineers as they ramp up their careers—careers that I know will be not only personally rewarding but also invaluable to the Nation," President Barack Obama said in a White House release.

New National Cancer Advisory Board Member Named

Dr. Tyler Jacks Dr. Tyler Jacks

Last week, President Barack Obama announced his intention to appoint Dr. Tyler Jacks to the National Cancer Advisory Board (NCAB). The NCAB is an 18-member advisory body that meets quarterly and advises the Department of Health and Human Services secretary and the NCI director on NCI activities.

Dr. Jacks is the director of the Koch Institute for Integrative Cancer Research and the David H. Koch Professor of Biology at the Massachusetts Institute of Technology (MIT). He is also an investigator with the Howard Hughes Medical Institute.

Following postdoctoral training at MIT's Whitehead Institute for Biomedical Research, Dr. Jacks joined the MIT faculty in the Center for Cancer Research and the Department of Biology in 1992. He has pioneered the use of technology to study cancer-associated genes and to create animal models of many human cancer types, including cancers of the lung, pancreas, brain, and ovaries.

Dr. Jacks has also served on NCI's Board of Scientific Advisors and the American Association for Cancer Research's Board of Directors. He is a past president of AACR and was elected to both the National Academy of Sciences and the Institute of Medicine in 2009.

Dr. Jacks received his B.A. in biology from Harvard University and Ph.D. in biochemistry from the University of California, San Francisco.

The White House announced the appointment of five new NCAB members earlier this year: Drs. Marcia Cruz-Correa, Kevin J. Cullen, Olufunmilayo F. Olopade, Jonathan M. Samet, and William R. Sellers.

Cyber-Seminar Will Address Cancer Control and Prevention for Latino Populations

Research to Reality bannerThe October 18 NCI Research to Reality cyber-seminar will feature Dr. Patricia Miranda, assistant professor of Health Policy and Administration at Pennsylvania State University, who will discuss her research on cancer disparities among Latinos and the need for targeted communications and interventions.

In addition, Dr. Maria Fernandez, an associate professor of health promotion and behavioral sciences at the University of Texas-Houston, will share her work with the National Center for Farmworker Health and its adaptation and implementation of an evidence-based breast and cervical cancer program in a variety of settings in Texas.

For more information and to register for this event, visit the R2R website, where you can watch presentations and join the discussions. This cyber-seminar will be archived on the R2R website approximately 1 week after the presentation. If you missed any of the past cyber-seminars, you can view them in the R2R archive.

Small Businesses: Apply for Cancer Research Funding by 
November 7

NCI Small Business Innovation Research and Small Business Technology Transfer bannerNCI's Small Business Innovation Research (SBIR) Program recently announced $8 million in new contract funding opportunities to assist small businesses with cancer research and technology development. The 12 new contract funding opportunities represent NCI scientific priorities that are ripe for commercialization. The opportunities range across novel technology areas and include anticancer agents, diagnostics, radiotherapy, device development, nanotechnology-based sensors, and imaging technology.

The deadline for all fiscal year 2012 contract topic proposals is November 7.

Among the opportunities announced are three NIH Technology Transfer (TT) inventions released as contract topics. The goal of each SBIR-TT topic is to identify a small business that can obtain SBIR funding and licenses. Ultimately, the business should perform the necessary research and development to advance the technology toward commercialization.