Good morning, Congressman Burton and Members of the Committee. I am Richard Kaplan,
M.D., of the National Cancer Institute (NCI). I am a Senior Investigator in the Cancer
Therapy Evaluation Program and I coordinate NCI's extramural clinical research on prostate cancer treatment.
I am accompanied today by Jeffrey White, M.D., Director of the NCIs Office of Cancer
Complementary and Alternative Medicine.
I am pleased to appear before you today to describe NCI's prostate cancer
research program and our growing interest in complementary and alternative approaches to
prostate and other cancers. The Congress has asked NIH to make prostate cancer a top
priority in allocating funding increases; to accelerate spending on prostate cancer; and
to consult closely with the research community. Under Dr. Klausner's leadership, NCI
has undertaken a vigorous effort to respond in all of these areas.
The nature and magnitude of the burden of prostate cancer has been tracked by NCI's surveillance
program, and we estimate that about 180,000 men will be newly diagnosed with prostate
cancer this year and about 37,000 will die. Prostate cancer exacts a particularly
devastating toll on African American men; incidence rates are substantially higher among
African Americans, and mortality rates in African American men remain more than twice as
high as rates in white men.
This catalogue of statistics, while accurate, does little to convey the very real pain,
fear, and uncertainty experienced by every man who is diagnosed with prostate cancer.
Despite advances over the past decade, our treatments for prostate cancer are inadequate,
the side effects of treatment are significant and often unacceptable, and troubling
questions remain about the efficacy of early detection for the disease. Every day, too
many men in the United States
hear the life-changing words "You have prostate
cancer." Every day, too many men are faced with the agonizing
decisions of how best to treat their prostate cancer. And every day, too many men are
dying too young of this disease. The limited knowledge about the causes of prostate
cancer, how it may be prevented, and how to treat it successfully demand a broad, robust,
and clearly articulated approach to research.
At NCI, prostate cancer research funding increased significantly from a 1998 level of
$86.9 million to a current projection of $141.5 million in 1999. At the request of
Congress, NIH developed a plan for a coordinated, trans-NIH prostate cancer research
initiative outlined in Planning for Prostate Cancer Research: Five Year Professional
Judgment Estimates. A copy of this 5-Year Plan has been provided to you. This report
describes prostate cancer research opportunities across NIH from 1999 through 2003.
Without regard for economic constraints or other competing priorities of the NIH
or the Federal government, we estimate NCI could support $340 million, and NIH in total
could support $420 million worth of targeted prostate cancer research by FY 2003.
The NCI is the lead NIH institute for prostate cancer research. Ongoing and future
research initiatives have the potential to directly improve the length and quality of life
of prostate cancer patients and survivors, as well as those at risk for the disease.
Indeed, fully 70 percent of the research opportunities presented here are targeted at
clinical or translational research that would have a direct impact on patients, survivors,
and at-risk men.
The NCI has aggressively sought participation from non-government researchers,
advocates, and patients in reviewing the prostate cancer research portfolio and charting a
plan for a vigorous expansion of the prostate cancer research program. Over two years ago,
we initiated a disease-specific planning process called a progress review group or PRG.
The Prostate Cancer PRG involved scores of individuals from all over the country --
scientists, clinicians, and advocates--and challenged the prostate cancer research
community and the NCI to review our current prostate cancer research portfolio, to develop
a prioritized set of questions that needed to be answered and resources that needed to be
developed or applied, and to provide a vision and chart a course for research and progress
in prostate cancer. The PRG report was presented to the NCI last September and in the 12
months since then we have acted to implement a plan that we believe will fulfill the
vision of progress articulated by the PRG. A copy of the report has been provided to you.
In all of our planning phases we have involved a variety of members of the prostate
cancer communities including researchers, clinicians and advocates. To ensure that the
professional and advocacy groups were fully represented, the PRG invited the input of 32 "stakeholder" groups that
represented both professional societies and advocacy organizations and groups.
We have begun, in an aggressive way, to accelerate funding for prostate cancer.
- We have identified more than 20 initiatives through which high priority areas can be
addressed and a special section of the NCI Web site serves to bring these to the attention
of researchers and the public.
- We have further emphasized the importance of accelerating the pace of progress against
prostate cancer by promising applicants that prostate cancer grant applications will have
priority for so-called exception funding. That is, every effort will be made to fund
worthy applications in the identified high-priority research areas even when peer-review
assigned priority scores are not quite high enough to fit within conventional grant award
NCI has met with the representatives of the prostate cancer research community, the PRG,
and the leadership of professional societies, such as the American Urological Association,
in order to communicate these initiatives and to enlist the research communitys
support in responding to these opportunities.
Extensive outreach and advertising will alert the larger research community to these
opportunities to energize their participation in this prostate cancer research program.
The scientific opportunities we have identified fall into four major areas:
- Clinical Science-- the near term direct testing of new interventions in patients or
in those at risk for prostate cancer.
- Translational Science -- moving ideas from the laboratory to the point of clinical
testing, and determining how they should be applied and tested.
- Risk, Burdens & Outcomes Science -- attempting to ask critical questions about
cause, the unequal levels of cancer in different populations, outcomes and survivorship.
- Basic research and discovery -- longer term investments in gaining insight into the
development and biology of prostate cancer and the development of models for study.
Let me illustrate with a few examples of these new initiatives. In the area of clinical
trials for patients with prostate cancer, we need to test new approaches and new agents
aimed at a variety of clinical situations. We have established Prostate Cancer "Quick Trials," a new granting
program to provide a rapid, streamlined funding mechanism for moving novel new ideas for
therapeutic interventions into Phase I and II clinical trials for prostate cancer. This
program has been set up in recognition of the urgent need for new types of interventions
that are effective at different stages of prostate cancer, as well as the growing number
of therapeutic ideas that are ready to be tested in patients.
In this type of project, where it is necessary to evaluate untested leads in the
absence of preliminary data, conventional grant application and review procedures are not
well suited. Quick Trials utilizes a process for rapid approval of early clinical trials.
The NCI's goals are to increase the number of patients participating
in early clinical trials by two to three-fold and to initiate 10-15 new trials per year
through this accelerated mechanism. In addition, this year through NCI's Cancer Therapy
Evaluation Program, we will initiate approximately 35 new Phase I/II trials in Prostate
Cancer with agents directed against a number of particularly promising molecular targets
and mechanisms. These targets include:
angiogenesis and metastasis, the processes by which cancers induce new blood-vessel
formation, invade these blood vessels, and spread throughout the body;
growth factors and their receptors, which mediate growth signals to cancer cells; and
tissue-specific genes expressed selectively in prostate or prostate cancer cells, thus
allowing for the targeting of tumor-killing modalities to these cells.
We will test:
- Novel small molecule drugs
- Specific antibodies
- Virus-based gene therapy
- Targeted radiation sensitizers
Compared to the current level of effort, this plan could more than double the number of
early clinical trials in prostate cancer in the first year, with another doubling
projected in the next four years as per the full professional judgment estimate presented
by Dr. Klausner last June.
This year, we will activate at least 5 new multi-center phase III clinical trials in
prostate cancer that will attempt to optimize and test new hormonal and chemotherapeutic
approaches for the most common clinical presentations of the disease, including:
- adjuvant therapy in the setting of primary surgical or radiation treatment;
- neo-adjuvant therapy, which has shown promising results in reducing the mortality from
locally advanced prostate cancer;
- treatment after hormone therapy;
- treatment in the setting of rising PSA levels after definitive local therapy; and
- advanced disease, particularly directed at bony metastases.
With this initial ramp up in clinical trials, we project the ability to double the
number again over the following four years.
We have initiated a new program creating a drug development process that enables
investigators to advance novel molecules to clinical trials when they have not yet found a
pharmaceutical or biotechnology industry partner with the necessary resources. We do this
by giving academic investigators access, on a competitive basis, to NCI's preclinical drug
development resources and expertise. Investigators who have molecules that hold promise
for cancer treatment, but without access to the development resources required for
initiation of clinical studies, are invited to submit applications twice a year. Those
selected for support are assisted with necessary development steps to enable
Investigational New Drug Application (IND) filing with the Food and Drug Administration
and to begin initiation of proof-of-principle clinical trials. For FY 1999, our goal is
the development of three to five new therapeutic agents, each relevant to prostate cancer.
Projects already approved include development of a bioreductive compound with potential as
a radio- and chemo-sensitizer, and a gene-therapy approach that will convert inactive
pro-drugs into toxic agents within prostate cancer cells. Over five years, 15 new
therapeutic agents for prostate cancer could potentially be developed if sufficient
resources are available.
The NCI is moving very quickly in important directions to develop CAM information and
expand research opportunities for CAM investigators. These activities are broad in scope
and include strengthening our relationship with the National Center for Complementary and
Alternative Medicine (NCCAM), the careful evaluation of CAM therapies, and the development
of accurate CAM information for the public. One goal shared by the NCI, NCCAM, and other
Institutes is to establish Centers for CAM Research that would provide the resources
necessary for the rigorous scientific study of CAM approaches, as well as Specialized
Research Centers to investigate the biological effects of botanicals, including those that
are available as dietary supplements.
Several studies of CAM approaches are already underway. NCI - sponsored projects
recently have suggested that both vitamin E and selenium supplements can safely prevent
prostate and other cancers. More investigation is indicated and NCI continues to support
several studies addressing effectiveness in the prevention of prostate cancer by lycopene
and dietary soy, as well as vitamin E and selenium.
To enhance our collaboration with the CAM community toward bringing effective
prevention strategies and therapies to cancer patients we worked with NCCAM to establish
the federally-chartered Cancer Advisory Panel
(CAP-CAM). The CAP-CAM meets 2 to 3 times a year and draws its 15 members from a broad
range of experts from the conventional and CAM cancer research community. This group will
review and evaluate summaries of evidence for CAM cancer approaches submitted by
practitioners, make recommendations on whether and how these evaluations should be
followed up, and be available to observe and provide advice about studies supported by the
NCCAM and NCI, and about communication of the results of those studies. The panel affords
CAM practitioners the opportunity to submit retrospective analyses of data from patients
treated with a specific modality and to allow an expert panel of CAM and conventional
scientists to assess possible therapeutic benefit. This is formally known as the Best Case
Series (BCS). The CAPCAM held its first meeting on July 8-9, 1999, in Bethesda, MD. Panel
members discussed the scope of their advisory role and assessed presentations of two Best
Case Series. The CAPCAMs recommendations were: additional study of a specific
dietary supplement as a treatment for non-small cell lung cancer, currently provided by
the Connecticut Institute of Aging and Cancer; and further exploration of homeopathic
cancer treatments, provided by the PB Homeopathic Research Foundation, Calcutta, India. We are enthusiastic that this group can work
collaboratively in a new partnership between the conventional and CAM cancer research
Direction of Future Efforts
A number of additional central questions about prostate cancer have been identified, as
well as potential strategies to address them. These include:
- Testing promising preventive agents, particularly in high risk individuals;
- Developing new, predictive molecular diagnostics;
- Validating current and new early detection markers;
- The linkage of new imaging technology to directing therapy and assessing its effects
without invasive procedures;
- Epidemiologic studies to attempt to systematically identify correlates of the
profound geographic and population differences in prostate cancer rates; and
- Developing new animal models that faithfully reproduce human prostate cancer in order to
better understand tumor development and spread, and to better test preventive and
All of these opportunities build on a strong base of existing prostate cancer research
- The Cancer Genome Anatomy Project (CGAP), the goals of which are to build an index of
all genes that are expressed in tumors and support development of new technologies that
will allow high throughput analysis of gene and protein expression as well as mutation
detection. The tumor type with the highest representation in the early stages of the CGAP
effort is prostate cancer. NCI has facilitated investigator collaborations of
interdisciplinary studies following the recent discovery of a susceptibility gene on
chromosome 1. Leads from this effort may help to clarify genetic and gene-environment
interactions responsible for black-white differences in risk.
- NCI funded (in total or in part) 246 clinical trials in prostate cancer, including 80
Phase III studies and 37 Phase II studies. NCI clinical studies in prostate cancer have
significant African-American participation. One NCI study shows that 14.7 percent of men
enrolled onto NCI sponsored prostate cancer treatment trials are African American while
10.3 percent of Americans diagnosed with prostate cancer are African American.
- NCIs ongoing Prostate Cancer Prevention Trial (PCPT) involves 18,000 healthy men
over the age of 55 to determine if the drug finasteride can prevent prostate cancer.
- NCIs ongoing Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)
is assessing the efficacy of prostate cancer screening. New PLCO sites are being added to
enhance minority patient accrual. NCI also is co-sponsoring with the Veterans
Administration the PIVOT trial in which "watchful waiting" is being compared in
terms of outcome with surgical removal of the prostate. This trial is intended to
determine whether conservative treatment of localized disease may be an acceptable
alternative to surgery.
- NCI staff analyzing the Surveillance and End Results (SEER) Program data have shown that
there are tremendously differing patterns of care among black and white men with prostate
cancer. Encouragingly, however, NCI staff and the Department of Defense have collaborated
in a study of treatment data and shown that equal treatment yields equal outcome within
disease stages. This finding suggests that NCI efforts to improve prevention, diagnosis,
and treatment of this disease have the potential to benefit all patients equally.
- NCI, along with the American Cancer Society and the Centers for Disease Control and
Prevention sponsored a Leadership Conference on Prostate Cancer in the African-American
Community in November of 1997. Developed in cooperation with the 100 Black Men of America,
the Intercultural Cancer Council, the National Black Leadership on Cancer, and the
National Prostate Cancer Coalition, the conference represented a significant step toward
developing a strategy for the full participation of African Americans in prostate cancer
research and control.
- In addition, NCI recently conducted a large interview-based study of prostate cancer in
African Americans and whites. Analysis of the results has not thus far revealed any
specific factor that could explain the racial differences in risk. However, further
studies are underway, including an extensive evaluation of the role of different
components of the diet.
Communicating with cancer patients, individuals at high risk for cancer, the general
public, and the health care community is a central component of NCIs mission and
mandate. For prostate cancer, the institute communicates information to all of those
groups, as well as to the cancer research community.
Materials available from NCI, including print, video, and web products, range from
basic information about the disease, information about research now ongoing to improve
understanding and management of the disease, and information for men about early detection
and treatment options.
One of the most recent communications initiatives is a partnership with the prostate
cancer advocacy organization, US TOO, to develop a national communications initiative,
called Know Your Options, to better inform men and their families about the
disease. The initiative is based on an information package or kit that provides a solid
base of information about prostate cancer to help US TOO chapters work with their hometown
media. The media, in turn, use the information provided by US TOO with the NCI endorsement
to keep their readers, listeners, and viewers informed about the disease. The kit includes
the latest medical and scientific information available, as well as information about
where US TOO chapter leaders can go for more information, advice, and help.
In addition, information specialists from the NCI-sponsored Cancer Information Service
provide more than 60,000 people annually with information about prostate cancer,
information about research on the disease, information about screening and treatment
options, and information about coping with physical and psychological side effects of the
disease and its treatment. The NCI web site provides information about prostate cancer
clinical trials as well as information about treatment options for every stage of the
NCI is currently working with the Centers for Disease Control and Prevention and with
the Health Care Financing Administration to develop an educational video for men on issues
they could face with regard to prostate cancer screening, diagnosis, and treatment. The
video, intended to be relevant to a general male audience, will be developed to have
special relevance to African-American men. The video will provide educational material on
what men need to know about prostate cancer screening options, what they need to know
about diagnostic follow-up if a screening test is positive, and what they need to know
about treatment options if the diagnosis is positive.
NCIs basic print product about the disease, What You Need to Know about
Prostate Cancer, is now available on the web as well. It provides information about
prostate cancer; its symptoms, diagnosis, staging and treatment; clinical trials; side
effects of treatment; nutrition and other support for prostate cancer patients; and what
prostate cancer research holds for the future. A new publication from NCI,
Understanding Prostate Changes: A Health Guide for All Men, will soon be available on
the web too. It covers all aspects of prostate cancer in more depth than the basic
booklet, but also describes non-cancerous prostate conditions. Another product in
development, called Prostate Cancer Treatment: Know Your Options, will be published
in print format soon and will also be available on the NCI web site.
NCI is communicating vigorously with the cancer research community. Earlier this year,
NCI staff described all of the prostate cancer research initiatives that exist at the
institute, and placed that information on its web site. The institute then promoted the
availability of that information and issued an invitation for grant applications from the
scientific community. The promotion of the information on the web site included the
placement of advertisements in major scientific journals, the distribution of packets of
information to the nations cancer centers, and the distribution of information
through direct mail to cancer investigators. Since the promotion began in late February,
the web page listing prostate cancer grant opportunities has had thousands of hits from
those seeking information about the grant opportunities.
Mr. Chairman, I appreciate the level of interest this Committee has shown in prostate
cancer. I hope my testimony demonstrates NCIs commitment to advancing our knowledge
about prostate cancer as rapidly as possible. Our activities, and specifically Dr.
Klausners leadership efforts, over the past year have invigorated the prostate
cancer research community. It is this essential partnership between NIH, other funders and
that research community that will successfully accomplish the ambitious goals of this
plan. I would be pleased to answer any questions you may have.
National Cancer Institute Websites
To access electronic information about prostate cancer from NCI visit our web site at: www.nci.nih.gov
The National Institutes of Health Report, Planning for Prostate Cancer Research will be posted: www.nci.nih.gov/prostateplan.html
Prostate Cancer Initiatives is available at:
The Prostate Cancer Progress Review Group Report is available at: