On November 10, Health and Human Services (HHS) Secretary Tommy G. Thompson announced the launch of the National Network of Tobacco Cessation Quitlines, a telephone-based smoking cessation program. The toll-free access number - 1-800-QUITNOW (1-800-784-8669) - will put callers in touch with local programs that can help them give up tobacco. In addition, the HHS Web site - www.smokefree.gov - offers online smoking cessation advice and downloadable information. The Web site was created by the Tobacco Control Research Branch of the National Cancer Institute (NCI), with contributions from the Centers for Disease Control and Prevention and the American Cancer Society.

The National Network of Tobacco Cessation Quitlines state/federal partnership is the first effort of a larger collaboration that has the potential to have a major public health benefit. With one easy-to-remember number, tobacco users in every state will have the tools and resources they need to quit smoking.

"What starts as a single puff can become a death sentence for millions of Americans," said Secretary Thompson. "Americans want to quit smoking, and they should quit smoking. These initiatives will help Americans kick the habit and save their own lives."

Quitlines offer advice, support, resources for cessation medications, and referrals to local cessation services. The national system will route callers, based on their area codes, to available state-run quitlines. Callers from states not currently providing quitline services will be routed to NCI's quitline, operated by the Cancer Information Service. It provides services in English and Spanish.

The www.smokefree.gov Web site includes an interactive map with toll-free state quitline numbers and offers instant messaging with an NCI tobacco cessation specialist. Other information, such as a step-by-step guide to managing the process of quitting and publications that can be downloaded, printed, or ordered, is available 24 hours a day.

"Not smoking is the best way to avoid smoking-caused illnesses. But quitting is the single most important step smokers can take to reduce the risk of many cancers and other diseases," said NCI Director Dr. Andrew C. von Eschenbach. "Smoking causes 440,000 premature deaths each year. It's associated with at least 14 types of cancer, including lung cancer, acute myeloid leukemia, and cancer of the larynx, cervix, prostate, pancreas, kidney, and bladder, among others."

"People smoke for a variety of reasons," continued Dr. von Eschenbach, "and different people need different resources as they try to stop smoking. The new National Network of Tobacco Cessation Quitlines provides access to trained quitline counselors across the country who can assist smokers in their efforts to quit, and www.smokefree.gov supports both immediate and long-term needs as people become nonsmokers."

Research published in the New England Journal of Medicine in 2002 shows that people who used quitlines in addition to self-help materials had double the cessation rates of people who used self-help materials alone. Many smokers are more likely to use telephone services than face-to-face programs because telephone services are more convenient. Quitline services also have the potential to reach large numbers of tobacco users, including low-income, rural, elderly, uninsured, and racial/ethnic populations who might not otherwise have access to cessation services.

One of NCI's important successes over the past several years has been the establishment of partnerships with other government agencies to help improve service to the public. The announcement earlier this month about expanded coverage by Medicare for several NCI-sponsored clinical trials is an excellent example of collaborations between sister health agencies to promote better cancer care.

Under the initiative, the Centers for Medicare and Medicaid Services (CMS) will pay for Medicare beneficiaries to receive off-label treatment with drugs already approved for specific indications in colorectal cancer: oxaliplatin (Eloxatin), irinotecan (Camptosar), bevacizumab (Avastin), and cetuximab (Erbitux). Coverage, however, is contingent upon the beneficiary's participation in designated NCI clinical trials.

This is new territory for CMS that expands on its traditional role as a third-party health care payer. By collaborating with NCI on this venture, CMS is supporting clinical trials that should provide more evidence upon which the agency can base future payment decisions. Indeed, the trials that will be included in this initiative will attempt to answer some important clinical questions that could have a significant impact on patient care.

Research has suggested that the drugs included in this effort may offer some improvement over, or be an alternative to, existing treatments for indications other than those for which they have received FDA approval. For example, in several early-stage trials, both cetuximab and bevacizumab have shown activity against pancreatic cancer - a malignancy for which there has been a dearth of new treatments - but neither drug is approved by the FDA for that indication. NCI has put forward, as a top priority to CMS, a clinical trial that will compare both of these drugs in treating pancreatic cancer. Other proposed trials include testing treatments for head and neck cancer, as well as several different treatment approaches for colorectal cancers at various stages and at various points in the treatment continuum (e.g., first-line, adjuvant). The trials for which CMS will provide expanded coverage will be finalized over the coming months.

Although none of these trials were designed in response to this initiative, CMS's involvement should help to speed patient accrual and improve patient retention by assuring Medicare participants that drug and related administration costs, as well as diagnostic and monitoring tests (e.g., scans, blood tests), will be covered by CMS when they are not specifically provided for free as part of the research. In return, CMS will receive valuable information to help guide the agency as it grapples with tough decisions on what new cancer treatments to cover at a time when the health care dollar garners far less than it used to.

As CMS Administrator Dr. Mark B. McClellan stated in announcing this new initiative, CMS is hoping to focus on ensuring the most prudent use of the increasingly stretched taxpayer dollar while also improving the quality of cancer care. NCI concurs with CMS that a collaboration based on providing sound medical evidence for the most effective therapies for appropriate patients is a worthy goal, and one with which this new partnership can advance more rapidly.

Dr. Andrew C. von Eschenbach
Director, National Cancer Institute

The Journal of the National Cancer Institute (JNCI) recently published Cancer Outcomes Research: The Arenas of Application. This monograph describes and evaluates the peer-reviewed literature in cancer outcomes research, identifies recent key contributions, and highlights challenges in applying scientific evidence to cancer care decision making. It also includes an assessment of the state of the science by NCI scientists and a discussion of future directions in this field.

Cancer outcomes research describes, interprets, and predicts the impact of interventions and other influences on final outcomes important to decision makers, including patients, clinicians, and policymakers. The monograph focuses on such patient-reported outcomes as health-related quality of life, perceptions of and satisfaction with health care, and the economic burden of cancer and its interventions, rather than more traditional outcomes such as survival and disease-free survival.

The monograph details how outcomes research enhances the knowledge base required for cancer care decision making and focuses on three areas of outcomes measurement: the macro-, meso-, and micro-levels. Macro-level studies explore trends in cancer-related outcomes and progress against cancer at the population level to inform policy and research. Meso-level studies include descriptive and analytical studies to better understand and improve cancer outcomes. Results of these studies influence decision making by patients, families, providers, payers, and organizations concerning safety, efficacy, and cost-effectiveness. Micro-level studies use patient-reported outcomes to improve patient-clinician communication and decision making and the overall quality of cancer care.

Warning About St. John's Wort for Gleevec Patients

St. John's wort, an over-the-counter treatment for depression, can cause unwanted side effects in cancer patients who are taking imatinib mesylate (Gleevec), according to a study in the October 2004 Clinical Pharmacology & Therapeutics. Researchers at the University of Pittsburgh and the University of Florida found that the plant derivative sped up imatinib metabolism and its removal from the blood by 44 percent, thereby weakening the standard and effective dose.

The study, funded in part by NCI, involved 12 healthy subjects between the ages of 20 and 51. They received 400 mg of imatinib on day 1 of the study, 300 mg of St. John's wort three times a day on days 4 through 17, and 400 mg of imatinib on day 15. After each dose of imatinib, serial blood samples were taken over a period of 72 hours to measure the drug's clearance from the blood stream.

Because of wide use of complementary and alternative medicines among cancer patients, the authors note that their results could have dire implications for patients on imatinib: Because the dose of imatinib in patients with chronic myelogenous leukemia is directly related to their response, St. John's wort could lead to treatment failure. "Concomitant use of any drugs that [stimulate CYP3A4]" - the liver enzyme that metabolizes imatinib - "may necessitate an increase in the imatinib dose to achieve therapeutic concentrations and to maintain clinical effectiveness," they wrote.

Mesenchymal Stem Cells Deliver Interferon Beta to Tumors

A particular type of stem cell may be an effective delivery vehicle for anticancer agents, targeting tumor cells while sparing healthy tissues, researchers from M.D. Anderson Cancer Center report. The researchers, funded in part by NCI, modified mesenchymal stem cells (MSCs) to carry interferon beta (IFN-β), a biologic agent that promotes cell death and slows tumor cell growth, but that is typically toxic at the levels needed to achieve these effects in patients. Intravenous delivery of these modified MSCs (MSC-IFN-β cells) in xenograft mouse models of breast cancer and melanoma prevented lung metastases and significantly extended survival compared with untreated control mice, the researchers reported in the November 3 JNCI. Treatment with standard IFN-β failed to prolong survival in either model.

The researchers noted several limitations of this use of MSCs. For example, although the researchers found no evidence of MSC-IFN-β cells engrafting in healthy tissues, because MSCs target wound sites, infused MSC-IFN-β cells could potentially engraft in any tissues that have been injured by recent surgery or other mechanisms. They advised that human clinical trials testing MSCs as targeted delivery agents should "exclude patients who have undergone surgery or invasive procedures or have had infections."

CCR Grand Rounds November 23: Dr. Judith A. Shell, Medical Family Therapist, Osceola Cancer Center, Kissimmee, Fla. "Symptom Management in Cancer- Related Sexual Dysfunction" November 30: Dr. Stephen J. Chanock, Section Head, Genomic Variation, Pediatric Oncology Branch; Director, Core Genotyping Facility, Advanced Technology Center, CCR, "SNPing Away at Cancer" CCR Grand Rounds are held 8:30 to 9:30 a.m. at the NIH campus in Bethesda, Md., in the Clinical Center's Lipsett Auditorium.

During the "Cancer and the Environment" seminar, four NIH scientists explained how the interaction between genes and the environment can lead to cancer and how researchers determine whether a particular substance causes cancer. Many of the greatest cancer risks - smoking, unhealthy diet, excessive alcohol consumption, and sedentary lifestyle - are under an individual's control. This seminar, however, focused on the threat caused by factors that individuals cannot control, including those in the air, water, and earth.

At the seminar, Dr. David Longfellow of NCI's Division of Cancer Biology explained how cancer-causing substances are identified and how scientists use animal models and laboratory tests to determine carcinogenicity. Dr. Ken Cantor of NCI's Division of Cancer Epidemiology and Genetics spoke about chemical carcinogens and epidemiological studies. The usual process, he explained, begins when a physician observes a cluster of cancer patients. This leads to quantitative studies, including environmental comparison studies, which compare risk by geographic area. Dr. Ed Trapido of NCI's Division of Cancer Control and Population Sciences explained how the environment and the genome interact, using examples from lung cancer research. Dr. Christopher Portier, associate director of the National Toxicology Program for the National Institute of Environmental Health Sciences, described how the mixture of substances humans are exposed to makes it difficult to study specific environmental hazards.

To encourage discussion between reporters and cancer scientists, the seminars are informal and are web-cast so that reporters who cannot attend in person can still participate; about 120 people watched the "Cancer and the Environment" seminar online. October's seminar was the tenth since the program began in the spring of 2002. Past topics have included molecular targets for cancer, epidemiology, nutrition, cancer vaccines, and statistics.

NCI plans to make the seminars monthly events, holding them in cities across the country in partnership with NCI-designated Cancer Centers. Past seminars have been held in the Washington, D.C., area. By holding the seminars in other cities, NCI hopes to reach a larger audience and strengthen ties with media across the country.

The next seminar, "Natural Products for Cancer," will be held on November 18 at NCI's Natural Products Branch in Frederick, Md., about 35 miles north of the main NIH campus. Scientists in this branch screen and analyze terrestrial and marine-based compounds and determine whether they have anticancer properties. For example, paclitaxel (Taxol), a drug used to treat several cancers, was developed from the bark of the Pacific yew tree. (See NCI Cancer Bulletin ³, Aug. 17, 2004.) Drs. Gordon Cragg and David Newman will explain how NCI collects natural specimens and tests their potential as cancer treatments. The seminar will also feature a tour of the biorepository and cancer cell line screening centers on the Frederick campus.

Seminars for 2005 are tentatively scheduled for the Memorial Sloan-Kettering Cancer Center in New York, the USC/Norris Cancer Center in Los Angeles, and the Fox Chase Cancer Center in Philadelphia on topics ranging from cancer health disparities to clinical trials enrollment.

NCI Board of Scientific Advisors November, 2004 Dr. Robert C. Young, BSA Chair, President, Fox Chase Cancer Center Dr. Kirby I. Bland, Fay Fletcher Kerner Professor and Chair, Department of Surgery; Deputy Director, Comprehensive Cancer Center, University of Alabama at Birmingham Dr. Kathleen M. Foley, Director, Pain and Palliative Care Service, Department of Neurology, Memorial Sloan Kettering Cancer Center Dr. Sanjiv S. Gambhir, Professor, Department of Radiology and Bio-X Program; Director, Molecular Imaging Program, Stanford University Dr. Joe W. Gray, Director, Division of Life Sciences; Associate Director, Biosciences, Lawrence Berkeley National Laboratory Dr. Mary J. Hendrix, President and Scientific Director, Children's Memorial Research Center; Professor of Pediatrics, Feinberg School of Medicine, Northwestern University Dr. Leroy E. Hood, President and Founder, Institute for Systems Biology Dr. Stanley J. Korsmeyer, Professor, Department of Pathology, Dana-Farber Cancer Institute Dr. Christopher J. Logothetis, Chair and Professor of Medicine, Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center Dr. Edith A. Perez, Professor of Medicine, Division of Hematology/Oncology, Mayo Medical School; Director, Breast Cancer Program, Mayo Clinic Dr. John D. Potter, Senior Vice President and Division Director, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center Dr. Ellen V. Sigal,* Chair, Friends of Cancer Research Dr. Jane C. Weeks, Assistant Professor, Department of Medical Oncology, Dana-Farber Cancer Institute * Reappointed

Dr. Leland Hartwell, Nobel laureate and director of the Fred Hutchinson Cancer Research Center in Seattle, began his presentation by noting that the case for early detection through biomarkers is founded in both economics and patient outcomes. He said that a more organized and systematic approach for discovering biomarkers for cancer exists than that which is currently available, and stated that even with existing technology, "If we take a divide-and-conquer strategy" beginning with 1,000 biomarker candidates and splitting the work among different laboratories, "we could end up with something in the order of 30 to 40 good things in the end."

The principle obstacles in this process, he noted, are a lack of reagents and a lack of standards within this research field. He called on NCI to lead and oversee a new biomarker initiative, and proposed a structure whereby centers are funded for focused work on reagents, technology, and informatics, with smaller pilot projects led by individual researchers.

BSA members were largely supportive of Dr. Hartwell's proposal, but identified key concerns that should be reviewed, including legal issues surrounding the collection of samples for biomarker testing; the size and nature of the patient population for this research; the ultimate cost during clinical trials of biomarker candidates; and the other programs and initiatives, such as the NIH Roadmap and the Early Detection Research Network, that should dovetail with this new effort.

Dr. Mark Clanton, NCI's deputy director of Cancer Care Delivery Systems, followed with an overview of health care quality assessment as context for future discussion. "The public health impact of cancer can really only change if we can increase and enhance the performance of the health care system," he said. Staff from NCI's Outcomes Research Branch in the Division of Cancer Control and Population Sciences then presented a summary of the research dissemination tools that NCI makes available to the health care community, the challenges in translating research into practice, and two programs to improve palliative health care in specific populations, with following discussion of the appropriate role for NCI in provider training and in evidence synthesis and dissemination.

BSA members had many suggestions for how to address these issues, including a report-card system in which clinicians have incentives to comply with standards of practice, NCI-funded "leverage research" that would be adopted by health care practitioners, and identification of interventions that have been effective in systems similar to that of health care in this country.

This funding opportunity will use the NIH cooperative agreement specialized center (U54) award mechanism.

For more information see: http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=2421.

Inquiries: Dr. Sanya A. Springfield - springfs@mail.nih.gov

Cooperative Planning Grant for Comprehensive Minority Institution/Cancer Center Partnership
RFA-CA-05-022
Letter of Intent Receipt Date: Jan. 22, 2005
Application Receipt Date: Feb. 22, 2005

This funding opportunity will use the NIH cooperative agreement specialized center (U56) award mechanism.

For more information see: http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=2422.

Inquiries: Dr. Sanya A. Springfield - springfs@mail.nih.gov

Strengthening Behavioral and Social Science in Medical Schools
RFA-OD-05-001
Letter of Intent Receipt Date: Dec. 10, 2004
Application Receipt Date: Jan. 19, 2005

This funding opportunity will use the NIH K07 award mechanism(s). For more information see: http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=2402.

Name of the Trial
Phase III Randomized Study of Induction Platinum-Based Chemotherapy and Radiotherapy with or without AE-941 (Neovastat) in Patients with Unresectable Stage IIIA or IIIB Non-Small Cell Lung Cancer (MDA-ID-99303). See the protocol summary at http://cancer.gov/clinicaltrials/MDA-ID-99303.

Principal Investigator
Dr. Charles Lu of the University of Texas M.D. Anderson Cancer Center

Why Is This Trial Important?
Patients who have advanced non-small cell lung cancer (NSCLC) that cannot be removed surgically (unresectable) are often treated with platinum-based chemotherapy agents and radiation therapy in an attempt to prolong their survival.

Like other solid tumors, NSCLC requires a constant supply of blood to grow. Drugs that block the formation of new blood vessels to tumors are called angiogenesis inhibitors. Such drugs may help cancer patients survive longer. In this trial, researchers are studying the ability of AE-941 (Neovastat), a liquid extract of shark cartilage that has angiogenesis inhibitor activity, to improve the survival of patients with unresectable NSCLC when given in combination with traditional chemotherapy and radiation therapy.

"What is different about this study is that we are using a standardized extract from cartilage instead of a drug devised from a single molecule," said Dr. Lu. "Thus, Neovastat may offer a combination of molecules that work together to inhibit angiogenesis."

"Data from animal studies support the hypothesis that this extract has antiangiogenic activity and that it may inhibit certain enzymes involved in cancer cell metastasis, such as matrix metalloproteinases 2, 9, and 12," Dr. Lu added.

Who Can Join This Trial?
Researchers seek to enroll 756 patients aged 18 and over who have been diagnosed with inoperable stage IIIA or IIIB NSCLC. See the full list of eligibility criteria for this trial at http://cancer.gov/clinicaltrials/MDA-ID-99303.

Where Is This Trial Taking Place?
Study sites in the United States, Canada, and Puerto Rico are enrolling patients in this trial. See the list of study sites at http://cancer.gov/clinicaltrials/MDA-ID-99303.

Who to Contact
See the list of study contacts at http://cancer.gov/clinicaltrials/MDA-ID-99303 or call the NCI's Cancer Infor-mation Service at 1-800-4-CANCER (1-800-422-6237). The call is toll-free and completely confidential.

"Pancreatic cancer is the fourth leading cause of cancer death in the United States," said Paula Kim, co-founder of PanCAN. "More than 31,000 people are diagnosed with pancreatic cancer every year, and it continues to be the cancer with the highest mortality. The map will enable researchers to find and search a comprehensive list of studies and projects relevant to pancreatic cancer."

Alliance for Nanotechnology in Cancer Moves Forward
The NCI Alliance for Nanotechnology in Cancer continues to build momentum with several events and program announcements. On Oct. 27, NCI and the Case Comprehensive Cancer Center, which includes The Cleveland Clinic Taussig Cancer Center and the Ireland Cancer Center at University Hospitals of Cleveland, co-sponsored a regional symposium to bring together local cancer and nanotechnology researchers to foster the interdisciplinary team-building needed to speed efforts in cancer nanotechnology. Dr. Harold L. Moses, director of the Vanderbilt-Ingram Comprehensive Cancer Center, and Dr. Chad Mirkin, director of the Northwestern University Institute for Nanotechnology, gave the keynote addresses. Other speakers included Dr. Miqin Zhang, of the University of Washington, Dr. Greg Lanza, of the Washington University School of Medicine, and Dr. James Baker, Jr., of the Center for Biologic Nanotechnology at the University of Michigan.

The next nanotechnology symposium will be held Feb. 22, 2005 at the Lombardi Comprehensive Cancer Center in Washington, D.C.

President's Cancer Panel Meets in Houston
The President's Cancer Panel continued its meetings on "Translating Research to Reduce the Burden of Cancer" on November 1 at the University of Texas M.D. Anderson Cancer Center. Testimony emphasized the challenges in moving cancer discoveries through the development-to-delivery continuum, including the need for cultural shifts at multiple academic, regulatory, and institutional levels.

Participants also noted the existing imbalance between the numbers of researchers in basic science and translational research, and suggested the development of a national strategy to shift the emphasis between these disciplines, including transforming individual and team reward structures. They noted that this will also require a cultural shift and reevaluation of grant review criteria and assessments made by review committee members. The Specialized Programs of Research Excellence program was mentioned as a successful model for structuring translational research efforts.

Cancer.gov Offers Direct Links to NIH Roadmap Funding Opportunities
To ensure that cancer researchers have an opportunity to participate actively in the NIH Roadmap for Medical Research efforts, NCI has provided a new background link on its Web site: http://www.cancer.gov/researchandfunding/NIHRoadmap. The site contains a direct link to the many NIH Roadmap funding opportunities, including new initiatives and re-announcements.

Launched in September 2003 by NIH Director Dr. Elias Zerhouni, the NIH Roadmap is a series of far-reaching initiatives designed to transform the nation's medical research capabilities and speed the movement of research discoveries from the bench to the bedside. It provides a framework of the priorities that NIH must address to optimize its entire research portfolio and lays out a vision for a more efficient and productive system of medical research.

To view the current NIH Roadmap funding opportunities, go to: http://nihroadmap.nih.gov/grants/index.asp