Cancer researchers are striving to improve
patients; a point made clear by ideas presented at the 1998 American
Society Science Writers Seminar. Among the experimental
In most cases, chemotherapy drugs circulate
the doses that can be given safely are usually limited by side-effects.
For example, many chemotherapy drugs attack cells that are rapidly
unfortunately, that means they often damage bone marrow cells, which,
cancer cells, grow rapidly.
The chemotherapy gel being worked on by Dr.
at the Arizona Cancer Center is based on a simple desire: to
the killing power of chemotherapy drugs on tumors, while sparing normal
tissues from their toxic onslaught. In the first phase of tests in
patients, researchers used a mixture of cisplatin and epinephrine,
treatments for certain cancers. But in the gel experiment, doctors
to increase the concentration of chemotherapy drug inside the tumor to
between 10 and 100 times the level of standard treatment. Despite that
intense concentration of drug attacking the cancer, the total dose used
was a small fraction of standard treatment: from 5 to 20 mg, compared
160 to 220 mg for standard chemotherapy; so the patient's normal
were subjected to very little of the toxic drug.
More importantly, researchers say the
tactic worked. In one
82 patients with advanced metastatic cancers, 39 percent had complete
to the treatment, while an additional 11 percent had partial responses.
"It should be emphasized that in such a... group of tumors, it is
to encounter even one or two responses," says Dr. Garewal. "The
in the lesions is durable. It won't come back." He adds that overall
treatment was well-tolerated.
However, Dr. Garewal emphasizes that while
destroy individual tumors, the patients with metastatic disease were
cured, because new tumors eventually appeared that could not be treated
with gel injections. In particular, the strategy may not work for brain
tumors, because it causes swelling which could be dangerous within the
confines of the skull.
"It's a very clever idea," says Frank
McCormick, PhD, director
the University of California-San Francisco Cancer Center. He points out
that, even if it is not curative, the treatment could offer real
to patients with head and neck cancers by shrinking tumors that are
The gel is made from cow collagen, similar
to material used in
injections, but it has been re-engineered in order to produce some
properties. "It's based on collagen," says Dr. Garewal, "but the final
product is quite different. It took a lot of development work." The
important feature is the gel's response to body heat. While most
become softer at higher temperatures, this gel, which is a liquid at
temperature, solidifies at body temperature. That property means it can
be injected through a syringe directly into a tumor, where is hardens,
trapping the drug within the cancer growth. After the drug has done its
job, the collagen eventually dissolves.
The researchers are now pursuing a second
phase of trials to
effectiveness of the gel. One group of patients has recurrent head and
neck cancer. A separate test is underway on patients with liver tumors.
In order to get objective results, neither the researchers nor the
will know which patients are receiving gel injections containing active
chemotherapy and which are getting a placebo.
A new type of vaccine could also offer a
way to use unique
of cancer cells to focus an attack. Dr. Hildegund Ertl of the Wistar
in Philadelphia is studying vaccines made from the genetic material,
DNA, of cancers. She is concentrating on a gene known as p53, which is
mutated in many types of cancer.
Dr. Ertl says the surfaces of many cancer
cells are covered
amounts of the protein produced by p53, while normal cell surfaces
very little p53. The researchers attached the p53 gene to an altered
of a virus to make what is known as a "DNA vaccine." The idea is that
the vaccine is injected into the body, immune cells will recognize the
virus and the attached p53 gene as invaders and mount a counter-attack.
The hope is that the immune response would be concentrated on the
cells with high levels of p53 on their surfaces.
The technique has protected some laboratory
A combination of the DNA vaccine with other substances that boost the
system was able to shrink some established tumors in test
However, Dr. Ertl points out that the form
of the vaccine
far is not 100 effective, even in laboratory animals, so several years
of work remains before testing with people can even begin.
The American Cancer Society seminar also
heard of research at
Health Sciences University, where researchers are hoping to help some
patients by exploiting a unique feature of their blood cancer
The target of this work is a protein
molecule called Bcr-Abl.
an abnormal molecule related to enzymes that control cell growth. The
were attracted to Bcr-Abl because it appears only in chronic
leukemia, known as CML; normal cells don't have any Bcr-Abl.
The researchers developed a drug that would
block the Bcr-Abl
while not affecting any normal enzymes. "Our studies demonstrate that
compound kills cells that contain Bcr-Abl, but does not kill normal
says Dr. Brian Druker of OHSU. Tests in patients with CML are scheduled
to begin this year at OHSU, the University of California at Los
and M.D. Anderson Cancer Center in Houston, Texas.
New CML treatments are urgently needed;
one patient in five. But the ultimate promise of this work is not
to CML. Basic research is rapidly uncovering molecular abnormalities
are unique to other cancers. In each case, the researchers say, it may
be theoretically possible to identify targets for drugs that could kill
cancer cells, while leaving normal cells unaffected. However, they
that this line of research has yet to prove itself in tests on
These three innovations in cancer
therapy may still be
way from clinical use, but they represent just a few of the new ideas
tried in laboratories today, that someday may lead to more successful