Because of a long-time interest
in medical hyperthermia, on a recent trip to Houston, I visited
with Joan M. Bull, MD, professor at the University of Texas (UT)
Medical School and director of its Division of Oncology. Dr. Bull
is an unlikely advocate of an "alternative" approach to
cancer. She graduated with a BA in biology from Stanford University
and obtained her medical degree from Stanford Medical School. After
interning at the University of Chicago Hospital, she returned to
Stanford for a residency in Internal Medicine and also completed
a fellowship in medical oncology.
For the next ten years, Dr. Bull held research positions at the
National Cancer Institute (NCI), first as Medical Officer, then
Special Research Fellow, Senior Staff Fellow, and finally Senior
Investigator in the Division of Cancer Treatment. She worked on
the celebrated MOPP protocol for Hodgkin's disease with Dr. Vincent
J. DeVita, Jr., then the NCI Director (Moore 1973). It was while
she was at the National Cancer Institute – again at the suggestion
of Dr. DeVita – that she began to research the use of heat
against cancer. In 1980, she came to the University of Texas (UT)
Medical School in Houston as an associate professor in the Division
of Hematology/Oncology of the Department of Internal Medicine. There
she began her research program in whole body hyperthermia.
Dr. Bull is now a professor of Internal Medicine and, since 1995,
has been the Director of the Division of Medical Oncology. She is
presently also Director of the Oncology Clinic at Hermann Hospital,
which is an administratively separate institution that is physically
attached to the UT medical school. She is also an attending physician
at the M.D. Anderson Cancer Center (also in Houston) and is the
author of 91 PubMed-listed articles, most of which discuss the use
of heat as a cancer treatment.
With so many impressive credentials, it may seem odd to find her
included as one of the "complementary and alternative"
(CAM) practitioners in Houston. Dr. Bull herself rejects any suggestion
that she is an "alternative" practitioner. She is, after
all, thoroughly orthodox in her background and training. But her
abiding interest in heat therapy for cancer, as well as in treatments
that modulate the immune system, has unarguably led her in an unconventional
direction. She is offering something outside the mainstream, albeit
under Food and Drug Administration (FDA)-approved clinical trial
protocols at a major medical center.
I have heard the name Joan Bull in connection with hyperthermia
for many years. Her first studies of whole-body hyperthermia were
published in the 1970s (Bull 1979). But whereas other American practitioners
of this treatment have either retired or dropped out of the field,
Joan Bull has stuck with it, sometimes to the bemusement of her
colleagues, who cannot understand why she finds the field so compelling.
(I happen to share her enthusiasm for hyperthermia.) Here's a revealing
statistic: of the seven clinical trials of whole body hyperthermia
for cancer that are listed at the National Cancer Institute's clinical
trials database (www.clinicaltrials.gov),
all but one are being conducted by Dr. Bull! (The remaining one
is being run by a German research team.) So, for reasons that are
hard to fathom, Joan Bull now has the field of whole-body hyperthermia
almost entirely to herself in the American academic community.
I first met Dr. Bull at a Comprehensive Cancer Care conference in
Arlington, Virginia, in 2001. But my recent visit to Houston was
the first time that we had a chance to get to know one another and
for me to learn details about her work. She took time out from a
very busy schedule to talk about what she calls "thermal therapy."
(She avoids the word "hyperthermia" because it has two
separate and unrelated meanings in medicine and is thus ambiguous.
Many lay people also confuse hyperthermia with hypothermia, which
is a dangerous drop in body temperature such as may occur through
prolonged exposure to frigid outdoor temperatures.)
The first thing to understand is that everyone who seeks admission
to Dr. Bull's program at the University of Texas first has to be
enrolled in a formal FDA-approved clinical trial. There are presently
three such trials that are actively recruiting. (You can find more
details on these at www.clinicaltrials.gov.) They are as follows:
Chemotherapy with whole body hyperthermia for treatment-resistant
breast, endometrial, cervical, and ovarian cancers
2. Hyperthermia with chemotherapy to treat inoperable or metastatic
neuroendocrine tumors; small cell lung cancer; non-small cell
lung cancer; gastric cancer
3. Hyperthermia with chemotherapy for locally advanced or metastatic
us look in detail at trials #2 and #3, since they are most comprehensive.
Patients in these trials receive an intravenous infusion of the
FDA-approved drug gemcitabine (Gemzar®) over a period of 30
minutes on days 1 and 8 of the treatment. They also receive the
drug cisplatin by intravenous infusion over six hours on day 15,
followed by low-dose subcutaneous injections of the immune modulator
interferon-alfa on days 16 and 17. Patients then undergo long-duration,
fever-range whole body hyperthermia (thermal therapy) over six hours
plus more gemcitabine (Gemzar) over 30 minutes on day 17, as well
as daily, self-administered, low-dose interferon alpha injections.
This course of treatment is then repeated every four to five weeks,
assuming there is no disease progression or unacceptable toxicity.
This unique combination of fever-range whole body thermal therapy
(abbreviated FR-WB-TT) and chemotherapy is sometimes referred to
as "thermochemotherapy." Although Dr. Bull describes the
temperature as "low range," the body is actually heated
to a core temperature of 40º C (or 104º F), using a German-made
Heckel HT2000M radiant heat device. Some German CAM clinics raise
the temperature higher, but Dr. Bull believes that fever-range temperatures
are sufficient (along the lines of the cancer remissions effected
with fever therapy a century ago by William B. Coley, MD).
The synchronization of drugs and heat are very important for the
outcome, as Dr. Bull wrote in a 2008 paper: "The relative timing
of agents in multiple modality treatments is critically important
in achieving tumor control or cures, and in reducing toxicity. Optimizing
the relative timing of multiple agents in thermochemotherapy allows
use of lower drug doses to achieve maximal anti-tumor efficacy and
minimal toxicity" (Bull 2008).
Dr. Bull's website gives the following description of the process:
array of heat lamps within a soft-sided, reflective chamber directs
infrared energy through the skin. Once the desired body temperature
has been reached, the space blanket-like sides of the chamber
are wrapped around the patient to maintain the temperature for
6 [six] hours. The temperature can be adjusted as necessary by
further use of the lamps for additional heating or opening of
the blankets to facilitate cooling. Patients are administered
a light sedative to assist with relaxation and to remove any irritability
resulting from the fever-like state. Care is given to maintain
adequate hydration throughout the procedure.
With this whole body heating device,
an array of heat lamps within a soft-sided, reflective chamber directs
infrared energy through the patient's skin. Once the desired body
temperature has been reached, the space blanket-like sides of the
chamber are wrapped around the patient to maintain the desired temperature
for six hours. The target temperature can be adjusted as necessary
by further use of the lamps for additional heating or, conversely,
opening of the blankets to facilitate cooling. Patients are administered
a mild sedative, says Dr. Bull, to assist with relaxation and also
to remove any irritability that might result from their fever-like
state. Care is given to maintain adequate hydration throughout the
In the US, hyperthermia in general relies on devices that are approved
by the FDA, which currently classifies Dr. Bull's type of hyperthermia
machine as a "non-significant risk device." This means
that it does not pose any significant danger and can be studied
without FDA oversight, provided that the sponsor otherwise complies
with FDA requirements. As a general rule, non-significant risk devices
require only institutional review board (IRB) approval prior to
initiation of a clinical study.2 In addition, the chemotherapy
drugs that she uses are all FDA approved. Nevertheless, the FDA
considers the combination of whole body hyperthermia and chemotherapy
to be an investigational procedure. Her treatments are therefore
only administered according to research protocols that have been
approved by the UT-Houston Medical School's Committee for the Protection
of Human Subjects (i.e., their Institutional Review Board or IRB).
Since Dr. Bull is a professor at the University of Texas Medical
School, her clinical hyperthermia research only takes up a portion
of her time. She does not have a large staff or budget and, consequently,
can only help a select few patients. To my knowledge, this is the
only whole-body hyperthermia unit in operation in the entire United
States. The treatments are administered under the auspices of the
University of Texas, and everyone who is treated with hyperthermia
comes there as part of a clinical trial. The actual treatment is
given at Memorial Hermann Hospital, which is the headquarters of
a chain of a dozen or so ultra-modern hospitals in the Greater Houston
Hyperthermia is a promising treatment. For many years, it has been
widely available in Europe – indeed, it is the main reason
that many international patients flock to German clinics for treatment.
There, each hyperthermia session is likely to cost you thousands
of dollars, not to mention other associated costs. (The cost of
treatment at many CAM clinics nowadays runs around $1,000 per day.)
By contrast, the cost of the medical treatment for Joan Bull's experimental
heat treatment is essentially zero. Of course, this does not mean
your final out-of-pocket expenses will be zero. You may face considerable
costs for lodging, food and other necessities or incidentals while
you and your loved ones are in Houston. Most importantly, you or
your insurance company must pay for the radiological, physiological,
and laboratory blood work evaluations prior to protocol entry, as
well as for the standard chemotherapy given in the Oncology Clinic
prior to the thermal treatment, and the follow-up radiological and
laboratory evaluations during the protocol therapy. (See Dr. Bull's
And, especially if the program is successful, you will have to be
in Houston for many days during the year. Thus, in a typical month,
you will need to be there at a minimum on days 1-4. This same schedule
will then be repeated five weeks later. Needless to say, living
within easy driving distance would be a big plus in terms of logistics.
In the trials, patients are also instructed on how to self-administer
daily "metronomic" injections of interferon-alpha. All
clinical trials have inclusion and exclusion criteria, and Joan
Bull's are no exception.
Patients who are accepted into the program then face an extensive
battery of diagnostic tests and charges for standard chemotherapy.
Although the actual cost of this is ~$10,000, it is generally paid
for by one's insurance. The heat treatment itself, as part of an
approved academic experiment, is paid for by taxpayer dollars. So,
generally speaking, if one has insurance, the cost to the patient
is restricted to personal expenses. This is an outpatient procedure,
and so patients and their family members have to secure housing
at a nearby hotel and pay for their own travel, meals, etc.
The combination of heat, chemotherapy, and immunotherapy is certainly
innovative, especially in the US, where the options for receiving
any form of hyperthermia are severely limited. But one thing you
should be aware of is that, unlike in Germany, where whole-body
hyperthermia (sometimes using identical equipment) is given once
or even twice per week, Dr. Bull only gives patients one whole-body
hyperthermia treatment per month. She told me that this not so much
a medical decision as an economic one. She does not have the staff
or the research funds to pay for a more frequent schedule of treatment.
In other words, she is doing what she can do within the constraints
placed on her by the economics of her situation.
Who benefits from the treatment? Understand, first of all, that
Dr. Bull only treats people with very advanced cancers. That said,
her best results have been with the following:
- Advanced gastric (stomach) cancer: she told me of a 3.5 year
- Advanced pancreatic cancer: she told me of a greater than fourteen-month
complete, biopsy-proven response;
- Small-cell lung cancer (SCLC): she had two cases that also survived
3.5 years, one of whom then died of cardiovascular disease without
any evidence of cancer.
- Another patient had a complete response that so far has lasted
more than a year and a half;
- Other neuroendocrine (hormone-producing) tumors.
In summary, Joan Bull is one of the best-known
and most highly honored academic scientists associated with the
use of an integrative or CAM technique in the US. She is the author
of nearly 100 Pub-Med articles on the topic of hyperthermia and
is internationally recognized as an expert on these topics. There
could be many advantages to being treated by her within the Texas
Medical Center, particularly since excellent conventional care of
every sort is available at her own and neighboring institutions.
visit to Joan Bull is part of a systematic survey I am conducting
of CAM or integrative cancer clinics in the US and abroad. These
visits then form the basis for the "Where to Go?" series
of reports available at my website: www.cancerdecisions.com
1. See Dr. Bull's website. Available at: http://www.uth.tmc.edu/thermaltherapy/ClinicTreatment.html.
Accessed May 27, 2008.
2. Investigational Device Exemption (IDE). Available at: http://www.ahc.umn.edu/research/ind-ide/IDE/home.html.
Accessed May 27, 2008.