This past year we recognized the 25th anniversary of the 1971 National
Cancer Act. It has been an historical year as we sought to evaluate this
Nation's investment in cancer research and assess the fruits of that
investment. This fall we were able to announce that for the first time since we
began to track the constant rise in cancer mortality rates over 60 years ago, we
had encouraging news. Sometime around 1990, we appeared to have reached
the peak in the mortality rate and for the past 5 years, overall age-adjusted
mortality rates have fallen. This includes the most common causes of cancer
deaths, lung, colorectal, breast and others. We believe that these encouraging
changes are the result of prevention, especially declining tobacco use among
American adults, early detection and better therapy--all of which are the fruits
of research. The burden of cancer is not shared equally within our society.
African Americans, for example, experience a 20-30 percent excess rate of
cancer death compared to white Americans. The latest mortality data include
a significant drop in cancer death in African Americans, that may be larger
than the decrease reported for white Americans. Despite this good news, we
continue to evaluate the causes for differential cancer incidence and mortality
among different racial and ethnic groups. Overall, these statistics, I believe,
tell us that our investment is paying off. They tell us what we can accomplish
but that we have much more to do.
Today, over 10 million Americans are cancer survivors. The majority of these
were diagnosed with cancer more than 5 years ago. In recognition of the
many unanswered questions that long-term cancer survivors face and the need
to do research to answer questions about medical and psychological
consequences, late recurrences, second cancers and long-term effects of
treatment, we are initiating a series of funding initiatives in this area.
Our fundamental discovery goal is to ultimately develop effective interactions
that reduce the incidence, morbidity and mortality of cancer. There is no one
intervention or even one type of intervention that will successfully conquer
the many diseases we call cancer. Our approach must be open and broad-based, aimed at
identifying those at risk and those with modifiable risk
factors, developing sensitive and predictive means of early detection, learning
to finally correctly diagnose each cancer so that the diagnosis predicts the
course of disease and dictates the choice of therapy. Cancer is a disease in
which one of the trillions of cells in our bodies gradually changes over time.
That cell is a crucible in which the interacting players of genes and
environment meet and produce the alterations that drive the behavior of each
cancer.
There are two ways to search for the causes of cancer. We can look from the
outside and scan the cell's environment for agents of cellular change. Some
have been easy to identify, such as the chemicals in tobacco which cause
multiple cancers and are responsible for 30 percent of all cancer deaths, or the
sexually transmitted virus, Human Papilloma Virus, responsible for 90
percent of cervical cancers. Environmental factors that can alter the risk of
cancer include diet, outside factors such as environmental chemicals and
radiation and the internal factors such as hormones and the chemical and
physical soup within each cell. We currently employ scores of epidemiologic
studies to search for connections between all of these factors and specific
cancers, to search out potentially avoidable risks for particular cancers.
More recently, we have learned to look within the cell at the differences
between individuals in order to explain why external risks are magnified or
reduced in different people. The identification of specific cancer
susceptibility genes that explain inherited risks continues to be a focus of
discovery. Over the past year, scientists have identified new inherited
susceptibility genes for skin cancer and the locus for the first prostate cancer
susceptibility gene. We have moved to push beyond the discovery of these
genes to fund studies to evaluate the interaction of these genes with
environmental, dietary and hormonal factors; to establish more precisely the
risk associated with specific alteration in specific genes; and to evaluate
chemical or surgical prevention strategies for high risk individuals. We have
designed a new research infrastructure called the Cancer Genetics Network
aimed at linking centers of excellence throughout the country to work together
as a network to develop protocols for critical studies in individuals at genetic
risk for cancer to address the many issues that this new aspect of oncology is
creating.
The ability to look at genetic changes in cancer cells offers an interesting twist
to the search for external causes of cancer--a type of reverse epidemiology.
Scientists are now exploring whether the fingerprint of particular types of
carcinogens can be found, much like the thief that leaves incriminating
evidence at the crime scene, to help us use the effects of environmental
carcinogens to identify the culprits. This has been recently demonstrated for
one of the carcinogens in tobacco smoke, as well as for a carcinogen that
causes liver cancer found contaminating certain foods.
Prevention in part, explains the drop in cancer mortality rates and prevention
will play an increasingly important role in the future. Prevention studies
range from evaluating behavioral intervention against tobacco use and for
healthful diets to pharmacologic interventions including drugs that block the
actions of hormones to prevent breast or prostate cancer, anti-inflammatory
agents to prevent colon and other GI cancers, vitamin derivatives to prevent
aerodigestive cancers, and others. In fact, we are testing 24 agents in 78
clinical trials aimed at preventing cancer, approaching it not as an event but as
a long and stoppable process.
The identification of infectious causes of cancer provides another type of
prevention opportunity. Based on major breakthroughs at the NCI, we have
made a commitment to proceed with the development and testing of a
multivalent vaccine against cancer causing strains of human papilloma virus--the first such
effort to vaccinate against an agent solely for the purpose of
preventing cancer.
Early detection of cancer remains a critical part of increasing survival and
enhancing the possibility of cure. The success of early detection depends
upon awareness, access and the availability of tests that are sensitive and
specific. All of the increase in breast cancer incidence that we saw through
the 1980s (now leveled off) was the result of an increased detection of early
disease and now 65 percent of breast cancer is found as localized disease
compared to less than 40 percent twenty years ago with a 5-year survival rate
of 92 percent. We are actually engaged in the evaluation of many new
imaging techniques for cancer detection and hope to set up a diagnostic
imaging research consortium to, for the first time, establish a stable group of
investigators to evaluate innovations in cancer imaging. We are vigorously
pursuing the development of better mammography, digital mammography,
MRI, and digital ultrasound and other non-invasive techniques, as well as
powerful new approaches to image analysis to both provide better sensitivity
to the detection of breast cancer and to clarify the majority of abnormal
mammograms which detect structures that are not breast cancer, thereby
reducing the false positive rate of breast cancer screening.
The final component of decreasing cancer mortality is improved treatment.
Clinical trials are the means by which we test and establish the best treatment
for cancer. We have continued to work with partners to assure that patients
have access to clinical trials, strengthening our cancer clinical trials agreement
with the Department of Defense and concluding a new agreement with the
Veterans Administration to integrate the VA medical system into the NCI
clinical trials and cancer centers network. We have embarked on a strategic
plan to restructure our clinical trials information system to create a modern
informatics base, developed in conjunction with the FDA and the International
Committee on Harmonization to develop electronic system for data on
adverse events and the use of common toxicity criteria. A single entry clinical
data reporting system will greatly facilitate these trials and the pilot testing for
this system will be completed by April. These efforts will improve the speed
and accuracy of reporting, produce resource savings and remove the
impediments of burdensome and cumbersome paperwork.
Critical to enhancing access to clinical trials is available information. We are
currently working with patient and consumer groups to rewrite the NCI PDQ
information system to be more inclusive of all trials, more user-friendly and
comprehensible and more accessible. The NCI Clinical Trials Evaluation
Program is currently sponsoring over 750 active clinical trials, including 258
phase I trials this year to test new drugs and therapeutics. These range from a
virus engineered to kill only cancer cells, to gene therapy, to immunologic
approaches to cancer, to photon-based therapy, and to new small compound
drugs directed against the cancer cells or the blood vessels that nourish them.
In addition, hundreds of other trials are conducted at NCI cancer centers and
through other funding mechanisms. This past year, 12 new drugs were
approved by the FDA for use in cancer and we anticipate over 30
Investigational New Drug Applications in 1997. In the biotechnology
industry, over 40 new agents are in clinical trials for cancer. Cancer is the
largest single target of this burgeoning industry.
Notable results of clinical trials over the past year include the demonstration
of a 30 percent reduction in mortality for adjuvant therapy in stage C colon
cancer translating into approximately 4000 lives saved each year and as these
benefits may extend to stage B patients, the benefits may be even greater.
Interferon has been demonstrated to be of benefit, at least in a significant
subset of patients with advanced melanoma. The markedly improved survival
of combination chemotherapy with radiation for nasopharyngeal cancer
resulted in a cooperative group clinical trial being halted early. Other
examples illustrate the incremental advances being made, each adding to
improved survival for patients with multiple types of cancer. These trials
examine new agents, new combinations of therapy and new ways of
delivering therapy such as neo-adjuvant treatment where chemotherapy, for
example, is given before rather than after surgery in order to improve surgical
success and even to allow less extensive surgery.
One recent therapeutic advance illustrates how cancer therapy is being altered
by our new understanding of the molecular characteristics of cancer.
Researchers at the NCI, in collaboration with extramural investigators, have
been testing new treatment regimens for a particularly aggressive form of
lymphoma. A 5-drug regimen resulted in an apparent cure, or long-term
remission in about 50 percent of the patients. The remainder either failed to
respond or rapidly relapsed. What was different? In virtually all of the
relapsed patients, their cancer cells harbored a mutation in the p53 gene, a
gene whose loss of function is implicated in over 50 percent of all human
cancer. What had been called one cancer was clearly at least two distinct
diseases. Recently, the investigators evaluated a newer regimen with three
additional drugs and have observed long-term remission, hopefully cure, in 90
percent of all of these patients.
This example illustrates a principle that is guiding a transformation in
oncology. We can begin to identify the defining characteristics of any cancer.
It is the set of alterations that will define the actual targets for therapy that is
designed rather than arrived at empirically and it is the molecular distinctions
between cancers that will allow us to tailor therapy to the right disease. In
addition, the alterations that distinguish a cancer from a normal cell offer us
the set of possibilities for biomarkers for early detection for stealth cancers,
such as ovarian, pancreatic, kidney and others. We have made great strides in
this critical area of molecular diagnostics but can do more. For that reason,
we have embarked on an ambitious project to identify all of the genes
expressed in cancer versus normal cells. We call this the Cancer Genome
Anatomy Project (CGAP) and its goals are two-fold: 1) to produce a full index
of expressed genes for normal, pre-malignant and malignant cells and, 2) to
help support the development, dissemination and application of new
technologies to apply these indices for the discovery of markers for cancer
detection, of discriminators for accurate diagnosis and choice of therapy and
of targets for new therapeutics and prevention. CGAP both builds on and is
complementary to the Human Genome Project and is being done through joint
intramural and extramural efforts. CGAP has been developed with explicit
annual milestones and will be a national resource that all can tap into via the
world-wide web. CGAP involves a collaborative effort with the National
Library of Medicine and the Department of Energy, as well as with industrial
partners.
Connecting the profound advances in basic sciences and epidemiology to the
clinic has been referred to as translational research. Over the years, the NCI
Cancer Centers Program has been a central component of the development
and realization of such research. One of my goals was to fully re-evaluate this
program to assure it best rewarded outstanding science and best facilitated
translational research at the many institutions capable of contributing to the
National Cancer Program. To this end, we commissioned and have received a
report from a blue ribbon panel which has proposed significant changes in the
guidelines, review processes, definitions and funding policies for a revitalized
Cancer Centers Program. We are now in the final stages of revising the
program to incorporate most of the recommendations of the review group.
Finally, the NCI is committed to fulfilling its role within the larger National
Cancer Program and we have strengthened and enhanced our many
interactions and collaborations with other agencies and private organizations,
with the research and clinical communities, with advocacy organizations and
the public.
The challenges and opportunities before us are great. To address these,Mr.
Chairman, the budget request for the National Cancer Institute for FY 1998
totals $2,217,482,000, an increase of $61,066,000. I am pleased to be able to
appear before the committee and look forward to answering any questions.