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The Cancer Advisory Panel (CAP) of the NIH Office of Alternative Medicine
(OAM) convened for its charter meeting at 8:30 a.m. on November 16, 1998,
at the Doubletree Hotel in Rockville, Maryland. Dr. Ernst Wynder presided
as Chair. The meeting was open to the public.
On this page
- Opening Remarks
- Relationships with the National Cancer Institute (NCI)
- Description of OAM
- Overview of NCI-funded Research Mechanisms
- Current CAM Research Projects
- Potential Projects
- Public Comment
- Potential Projects (continued)
- General Discussion
- Adjournment
CAP Members Present
- June Brazil, B.S.
- Fran Jacobs, R.N.
- Peter L. Choyke, M.D.
- Sheila M. Katz, M.D.
- Ian Coulter, Ph.D.
- Ralph W. Moss, Ph.D.
- James A. Crowell, Ph.D.
- Douglas L. Weed, M.D., Ph.D.
- Susan Ellenberg, Ph.D.
- Ernst L. Wynder, M.D.
- Richard M. Goldberg, M.D.
- James S. Gordon, M.D.
- Michael Hawkins, M.D.
- David J. Hufford, Ph.D.
OAM Staff Present
- Geoffrey P. Cheung, Ph.D.
- Wayne Jonas, M.D.
Staff of other NIH Components Present
- Bill Bunnag, CSR
- William Harlan, M.D., Office of the NIH Director
- Eugene G. Hayunga, OAM
- Cedric Long, NCI
- Raya Mandler, NCI
- Richard Nahin, M.D., OAM
- Kim Pham, NCI
- James M. Pluda, M.D., NCI
- Min Song, NCI
- Jeffrey D. White, M.D., NCI
- Robert Wittes, M.D., NCI
- Roy S. Wu, Ph.D., NCI
Others Present
- David DeRose, M.D., Ph.D. (Lifestyle Center of America, Sulphur, OK)
- Jonathan Radow, (F-D-C- Reports, Chevy Chase, MD)
- S. Elizabeth Clay, (United States House of Representatives, Washington,
DC)
- Kirsten Goldberg, (The Cancer Letter, Washington, DC)
- M. Richardson
- Harvey Sloane, M.D., (C&P Foundation, Bethesda, MD)
- William Kelley Eidems, (Options--People Against Cancer, Mt. Ranier, MD)
- Mary Mitchell, Sterling, VA
- M.J. Mitchell, Sterling, VA
- Charles, Simone, M.D.
- Joanne Mikla, (Food and Drug Administration, Rockville, MD)
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Call to Order
The charter meeting of the National Office of Alternative and Complementary
Medicine's Cancer Advisory Panel (CAP) was called to order at 8:30 a.m.
by Dr. Cheung.
I. Opening Remarks
Opening remarks were made by the chair of the CAP, Dr. Ernst Wynder,
who welcomed all the panel members. He noted that alternative therapies
were now being sought by practitioners and patients alike because conventional
medicines did not hold all the answers, and offered a brief overview of
diseases through the centuries whose etiologies either refuted existing
medical paradigms or whose successful treatment depended on unorthodox
therapies. Dr. Wynder outlined a plan to divide the CAP members into subcommittees
to explore different aspects of complementary and alternative medicine
(CAM); those committees would address the topics of quality of life, serve
as a media advisory panel, study how best to evaluate proposed topics
of study, and identify topics for fundamental research. Dr. Wynder concluded
by remarking that he viewed the CAP as an ombudsmen for the public and
for the scientific profession that will serve to identify what CAM procedures
are worthwhile, and what CAM procedures show little promise in disease
prevention and/or treatment. Panel members then had a brief discussion
in which they introduced themselves, described their fields of interest,
and indicated on which subcommittee they would like to serve. Top
II. Relationships with the National Cancer
Institute (NCI)
Dr. Wittes, Director of Cancer Treatment and Diagnosis at NCI, addressed
the panel about the role of the CAP in existing NCI structures, and the
areas in which the CAP could best support the NCI's work. He noted that
within cancer treatment (as well as other areas of medical interest) the
cultures of conventional medicine (CM) and CAM are viewed as two separate
entities, which is ultimately detrimental for both areas of science, as
well as for the patients seeking effective treatment. However, the CAP
will be able to do much to break communication barriers between the conventional
and alternative groups, and promote productive communication instead.
The existing divisiveness between the two groups currently hinders both
CM and CAM from acting in their fullest capacity in cancer treatment.
CAP's role with the NCI will need to be clearly defined; for instance,
although it will not be necessary to have CAP oversight on specific clinical
trials, CAP's general input about reconciling existing scientific protocol
with sometimes-unique CAM protocol will be invaluable. In response to
a question from Dr. Jonas, Dr. Wittes stated that he believed CAP would
help the NCI in thinking through their own research agenda, including
the evaluation of evidence and the readiness of CAM interventions for
clinical trials. He also noted that although a uniform methodology would
not be used in the evaluation of all treatments, it would be necessary
to ensure that whatever evaluation methodology was used provided the same
standard of investigation for both CM and CAM treatments. Dr. Wittes also
explained that, in response to criticism that the quality of information
was uneven, the NCI has recently pulled all CAM cancer information from
its web sites, and noted that he hoped CAP members could help in the assessment
of appropriate CAM materials to be included in this forum. He also observed
that stringent clinical protocol is already in place for ongoing studies,
and did not think that it would be productive to include CAP input into
a process until the need was demonstrated for this input. However, he
indicated that the CAP could prove effective in helping to resolve problems
with current systems, and in other realms of conflict resolution as the
need presents itself. Dr. Wittes also explained that the closure of the
Office of Alternative Medicine (OAM) and the opening of the National Center
for Complementary and Alternative Medicine (NCCAM) took place as a result
of direct Congressional action, and noted that the NCCAM will have a substantial
budget, along with the authority to fund research with grants. In responding
to an observation from Ian Coulter that the CAM community may become increasingly
wary of the CM community, Dr. Wittes answered that he hoped the conflict
would subside to a level typical of the biomedical community at large.
Dr. Wynder added that the discovery of a scientific principle or process
is always easier than its application, and therefore CAM will have to
outshine CM for a time in order to overcome the dissent and apathy that
often accompanies the development of a new scientific outlook. Top
III. Description of OAM
Dr. Jonas provided the CAP with an overview of the OAM's history and
role in the federally-mandated study of CAM for the benefit of the U.S.
public. He noted that communication is a vital element between CM and
CAM, and that communication will foster "good science" for the
public and for the community for which these topics are important. He
extended his personal thanks to the CAP members for lending their time
and expertise to the CAP.
Dr. Jonas described the relationship between CAM and cancer, noting that
almost half of all cancer patients will use some form of CAM while receiving
CM treatment, sometimes without letting their conventional practitioner
know of the CAM practices. A recent JAMA study noted that around 42% of
the U.S. population in general uses some form of CAM and spends some $25-27
billion on CAM treatment, much of which is not covered by existing medical
insurance. The present data on the safety and efficacy of CAM treatment
for cancer is minimal. The public needs better information on these subjects
in order to make informed decisions about their treatment.
Dr. Jonas identified the first priority as identifying CAM areas that
are ready for clinical trials, followed by the need to identify topics
and procedures in areas that are not yet ready for clinical trials and
that need additional developmental work. He outlined what he viewed as
the CAP's mission: (1) to review and evaluate summaries of evidence for
CAM cancer claims submitted by practitioners (and patients); (2) to make
recommendation to the OAM and the NCI on whether and how these evaluations
should be followed up; and (3) to be available to observe and provide
advice about studies supported by the OAM and NCI, and advise on how study
results should be communicated to others. In order to facilitate this
agenda, Dr. Jonas noted the need for ongoing discussions with the NCI
to become familiar with its practices and products, and reviewed past
meetings focused on communication issues between CM and CAM. Remarking
on the limited resources available for the enactment of this agenda, Dr.
Jonas asked the panel to think about where the resources could best be
spent in order to identify substances that may be ready for clinical trials.
Dr. Jonas noted that NCI already has a system in place for the development
of clinical trials, and stated that working out the mechanics of collaboration,
standards of documentation, sufficient outcome measures, comparison groups,
and studies reproducibility still need to be addressed. This will include
ensuring product standardization and quality and discussion of practice
issues when more than one CAM modality is being used in treatment. He
addressed the problem of releasing study results prematurely, which can
imply NIH support where none officially exists, and remarked that the
CAP would be useful in determining when study reports should be available
for public review. He asked the CAP members to consider what parameters
they would like to see in order to assist in the decision-making process
of identifying selecting substances for further study. Dr. Wittes described
the existing best-case series used by the NCI, which makes good use of
clearly quantifiable data, but which would not translate as effectively
for use by integrated treatment protocols. Dr. Jonas agreed that a best-case
series can yield valuable results, but that the costs of such a practice
for CAM treatment evaluations may outweigh the benefits. He also agreed
with a statement by Dr. Hufford that a negative finding--that a modality
or substance is not effective in treatment--is also beneficial, and touches
on public health issues of product safety and quality. He also agreed
that multi-disease products are an important topic for CAM study, especially
for integrative studies.
IV. Overview of NCI-funded Research Mechanisms
Dr. Wu presented an overview of the ways in which the federal government
supports NCI research--i.e., grants, cooperative agreements, and contracts.
Contracts are regarded as a procurement mechanism that are applied, directed,
and specified by the government, and that directly benefit the government.
In contrast, grants and cooperative agreements are classified as assistance
mechanisms. This differentiation impacts the way in which research activities
are solicited by the government.
Dr. Wu briefly reviewed the several different grant mechanisms currently
operational within the NIH. He noted that regular research grants (RO1
grants) are highly sought, and contain several subcategories, including
grants for young researchers, interactive research project grants, and
merit awards. Program Project Grants (PO1 grants) are centered around
a common theme and must have a minimum of three science projects in order
to qualify for grant funding. Cooperative Agreements (UO1 grants) require
a certain level of staff participation. Exploration/development grants
(R21 grants) encompass several different types of funding mechanisms,
including those for pilot studies, or those projects that are considered
high-risk/high-payoff prospects. Technology transfer grants are broadly
contained within the STTR grant and SBIR grant process. These grants are
available to small businesses in collaboration with academic institutions,
or for projects with promising prospects for commercialization. Phased
Innovation Awards (R21 and R33 grants) are used to encourage technological
development in the non-profit sector. Grants are also available for the
funding of conferences.
A brief discussion followed concerning the past and present funding activities
of the NCI and its relation to funding by the OAM and project recommendations
by the CAP . Dr. Cheung explained that all NIH Centers use the review
services offered by the Center for Scientific Review. Should the CAP recommend
a particular cancer-related CAM study, the facilities of the NCI would
be available for this study, and existing NCI infrastructures could be
utilized in the implementation of the prospective study; funding would
be provided by the OAM.
Top
V. Current CAM Research Projects
Dr. James Pluda, Senior Investigator, Cancer Treatment
Evaluation Program, National Cancer Institute
Shark Cartilage
Dr. Pluda offered an overview of a current study on the efficacy of
shark cartilage/shark cartilage products for cancer treatment. This study
was begun as a result of some preliminary data from 1982 suggesting that
shark cartilage may have some antiangiogenic effects in the treatment
of cancer. The NCI decided to collaborate on this study. Several drug
companies were contacted to see if they were interested in providing the
product for this study, and to assess the quality of their shark cartilage
product. Three companies indicated interest, and one company, Aeterna,
was finally selected to provide its product AE941 (Neovastet®) for
study. The NCI and FDA then held meetings to discuss the adequacy of the
shark cartilage product for the study, and to discuss any other FDA concerns
with the process. The initial trial of the shark cartilage product will
be carried out by MD Anderson, and initial results will be designed to
detect a 30-40% difference in survival rates between patients who had
shark cartilage included in their treatment and those who did not. (Shark
cartilage will be administered in conjunction with radiation therapy and
chemotherapy.)
A discussion followed on why shark cartilage was selected for study, and
whether another study, indicating that shark cartilage was ineffective
in cancer treatment, had been considered before this study was approved.
Factors that may affect the assessment of the efficacy of shark cartilage
include the trial design, patient selection, and how far along the cancer
has developed when treatment begins for the study. Dr. Pluda stated that
he viewed the primary endpoint for shark cartilage studies to be survival,
and that the study will allow for the collection of data on toxicity,
response rates, and other secondary endpoints. Dr. Moss expressed concern
that using shark cartilage in conjunction with radiation and chemotherapy
may skew the results against shark cartilage, but Dr. Pluda countered
that since participants in both arms are given the conventional treatment
and only one arm receives the shark cartilage, any improvement in survival
rates in the group taking shark cartilage may be significant. Dr. Pluda
also noted that in order to participate in the study, patients must agree
to accept conventional treatment along with the shark cartilage/shark
cartilage placebo, and that presently between 500 and 700 patients are
planned to be accrued on the study. Dr. Hawkins noted that the standard
of care is determined by the practitioner, and that in this trial, practitioners
had determined that conventional treatment was necessary. The complexity
of the methodological issues in this trial--including determining the
bioavailability of the active agent in the product being tested, the need
for more than one trial to determine a product's efficacy, the method
of CAM-care delivery impacting on the trial outcomes, and the viewpoints
of the discussants themselves in approaching the topic--were also briefly
reviewed by CAP members, and were noted to be examples of the types of
issues they would face in future discussions assessing CAM treatments
for cancer-related conditions.
Some discussion also focused on how to
deal with negative study findings, and how to determine if shark cartilage
products negatively impact conventional cancer treatment, given the large
numbers of people currently taking shark cartilage in addition to undergoing
conventional therapies.
Gonzalez (dietary/enzyme regimen)
Dr. Jonas provided an overview of the Gonzalez approach to cancer treatment,
which entails changes in diet, the consumption of a large amount of dietary
supplements and enzyme supplements, stress management, and other lifestyle
changes that Dr. Gonzalez has developed as a treatment protocol for cancer,
including pancreatic cancer. The NCI reviewed a best-case series derived
from Dr. Gonzalez's case studies. The NCI recommended a prospective study
of patients with advanced pancreatic cancer; this study was performed
by Dr. Gonzalez and has been submitted for publication. A two-arm trial
has been established to assess the Gonzalez regimen, which the OAM and
the NCI are helping to fund. A discussion of the factors used in selecting
the Gonzalez treatment for study and for patient selection followed, and
it was noted that patients would see Dr. Gonzalez at Columbia University.
CAP members also observed that this was a study of an integrative treatment
protocol, as well as a study of the effectiveness of a unique practitioner
and how his personal involvement in patient treatment may affect the trial
outcomes. Dr. Jonas agreed that this study will present an opportunity
to determine if one practitioner's successful treatment protocol can be
generalized and used by other practitioners with equal success, which
will necessitate careful record-keeping by the participating practitioners
in order to track exactly what care is being delivered within the treatment
protocol.
Green Tea
Dr. Crowell discussed studies of the efficacy of green tea in preventing,
reversing, or delaying early cancer from progressing. Studies are being
carried out in cooperation with a Japanese tea company (studying green
tea) and Lipton (studying black tea). A literature review suggests that
tea components have offered effective cancer treatment in a variety of
trials with a variety of animals, and the literature is very complete
on the range of these effects. The next step is now being taken in assessing
the efficacy of tea in cancer prevention for humans. Preclinical safety
testing has already been completed, and additional 90-day safety studies
are now being conducted with dogs and cats. Additional studies will be
carried out to determine safe doses that healthy people can take for extended
time periods. Studies are also being funded for the examination of topically-applied
green teas for skin cancers.
Discussion followed on what identified this study as something that should
be included under the CAM umbrella, instead of under the conventional
development of new drug therapies, and to what degree the OAM and the
CAP should concern themselves with cancer prevention as well as cancer
treatment. The tea studies were characterized as an example of a product
that bridged the gap between CAM and CM studies. Top
VI. Potential Projects
Dr. White briefly discussed the role of his office at the NCI, noting
that it would serve as an NCI liaison to the OAM, and would help to develop
a joint NCI/CAM agenda, and assist in the interface between the public,
the CAM community, and the oncology community about CAM cancer research.
He stated that the best-case series protocol has existed at NCI for a
number of years, and would serve as a useful tool in selecting potential
projects for further study; in answer to questions from CAP members, he
outlined some of the components that would be required in the inclusion
of a best-case series. He also said that practitioners may be interested
in making a best-case series to the CAP directly; CAP members then had
some discussion followed on how that would most efficiently occur.
Mistletoe
Dr. White provided an overview of the literature on mistletoe, a semi-parasitic
plant of the Loranthacea family that lives on several different species
of trees. It is the most widely-used CAM cancer treatment in Europe (especially
in Germany), and preclinical and clinical research have isolated some
of its active compounds. Animal studies and in vitro studies suggest that
mistletoe acts as an immunostimulant, and exhibits cytostatic, anti-metastatic,
and anti-angiogenic activity. A search of the cancer literature indicates
that mistletoe may have some effects against breast cancer, and may improve
survival rates (in contrast with receiving no treatment at all.) Several
mistletoe products are currently available, but it is not available over-the-counter
in Europe. Mistletoe extract is usually administered by subcutaneous injection.
A pilot study in Canada is currently underway to further investigate mistletoe's
efficacy in cancer treatment. Dr. Moss noted that he believed German scientists
would welcome the opportunity to cooperate in a U.S. mistletoe study.
Top
VII. Public Comment
Dr. DeRose commented that as a private physician working in a clinic
offering CAM therapies, he and his colleagues generally stayed away from
treating patients with cancer because of the lack of solid information
available about CAM cancer treatment. He felt that even the adjunctive
CAM therapies for cancer were not firmly enough grounded to use them in
his practice. He asked the CAP members how practitioners like himself
could be drawn into the process of verifying and promoting CAM cancer
treatment.
Dr. Eidem, author of a book titled The Doctor Who Cures Cancer, discussed
the work of Emmanuel Revici and his work in tumor reduction and pain relief.
He offered many quotes of prominent scientists who, over the decades,
have praised Dr. Revici's work in cancer treatment.
Ms. Clay, a legislative assistant to Rep. Dan Burton, spoke of the necessity
of ensuring that everyone understands the scientific criteria for CAM
studies and identifying whether a single standard of evidence exists for
all. She noted that further clarification is needed regarding the decision-making
process for therapies under consideration. She stated that additional
information is needed by the public about dietary supplements and how
current legislation does not allow for medical claims to be made for these
products.
Dr. Richardson offered an overview of the work currently underway at
the University of Texas center, and referenced reviews of some 30 therapies
on their website. She proposed the establishment of a database to collect
information online for prospective outcomes monitoring purposes, which
could be linked to their website. She also noted that help was needed
to obtain FDA approval for additional drug studies.
CAP members had a brief discussion following the public comment about
best-case studies and how to obtain the data which would support them.
It was also noted that best-case studies were a very time-consuming and
difficult process to document. Top
VIII. Potential Projects (continued)
Newcastle Disease Virus
Dr. White offered a summary of research around the Newcastle Disease
virus and its possible use in cancer treatment. It is an avian virus that
is minimally pathogenic to humans, and has been used in cancer treatment
since the 1970s. It is usually administered intralesionally or systemically.
Phylaxia, a Hungarian company, has produced a vaccine, MTH-68, which is
derived from Newcastle virus, and animal and in vitro studies suggest
that the vaccine exhibits some cytotoxicity activity and may stimulate
the production of cytokines. Three small randomized control trials with
MTH-68 indicate that the use of this vaccine may result in improved survival;
a larger Phase II study is currently underway, along with another study
of high-grade glioma patients in Israel.
Discussion followed about why the Newcastle virus studies would be considered
CAM instead of CM. Dr. Moss suggested that it qualified as CAM because
it is non-toxic, and that the idea of a virus as a treatment agent is
a novel concept that has not been embraced by established centers and
pharmaceutical companies, and Dr. Hufford concurred. Other discussion
focused on the logistical issues stemming from a study of this virus.
Top
IX. General Discussion
Dr. Wynder chaired a general "housekeeping" discussion of
how to best proceed in the future. It was agreed that the CAP would meet
three times every year, and that Dr. Cheung would collect potential dates
for future meetings from CAP members. Subcommittee appointments were also
made: (1) The media advisory committee will be comprised of Dr. Moss and
Dr. Hufford, with Dr. Moss serving as chair; (2) the Quality of Life committee
will have Fran Jacobs, June Brazil, and Dr. Hufford, with Ms. Jacobs serving
as chair; (3) the Research Committee will have Douglas Weed and Sheila
Katz, with Dr. Weed serving as chair; the Evaluation Committee will have
Richard Goldberg, Susan Ellenberg, Peter Choyke, and Sheila Katz, with
Michael Hawkins serving as chair; Ian Coulter will serve on a database
committee that will look at demographics, treatment variables, and related
topics.
To close the meeting, each CAP member offered his or her impressions of
the charter meeting and what he or she felt was important to consider
for future reference. It was generally agreed that this had been a productive
first meeting, and that there was significant potential for furthering
significant CAM contributions to cancer treatment. Panel members were
also asked to remember the "soft" side of cancer research--i.e.,
support groups and other psychological components of cancer treatment--and
other lifestyle options that may affect treatment outcomes. CAP members
also agreed that the challenges ahead were methodologically complex, and
that cancer is often a unique disease running a unique course in each
patient. The need to encourage young researchers to become involved in
CAM cancer research was also acknowledged.
Coordination with other NIH components and other outside institutions
was identified as a key component to success.
Top
X. Adjournment
The first meeting of the Cancer Advisory Panel was adjourned at 4:45
p.m.
We hereby certify that, to the best of our knowledge, the foregoing minutes
and supplements are accurate and complete.
| Geoffrey P. Cheung, Ph.D. |
Ernst L. Wynder, M.D. |
| Executive Secretary and Deputy Director, |
Chair, |
| National Center for Complementary
and Alternative Medicine, National Institutes of Health |
Cancer Advisory Panel for Complementary
and Alternative Medicine |
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