WASHINGTONThe possibility of spontaneous regression
suggests that immunotherapy is a valid route to pursue in kidney
cancer research, said Ronald M. Bukowski, MD, director of the
experimental therapeutics program at the Cleveland Clinic Cancer
Spontaneous regression is not common, but research suggests it may be
related to immune response, he said at the 1999 Kidney Cancer
Association Convention. Thus, immunotherapeutic measures to improve
immune response may prove to have value against the disease.
Such regressions tend to occur in lung metastases of kidney tumors in
patients who have had the primary tumor removed as well as in
patients who are not being treated. In 5% of these individuals, the
tumors shrink by themselves.
In a randomized, double-blind Canadian study in which kidney cancer
patients received gamma interferon or placebo, 6% of the placebo
group had regression of metastases, Dr. Bukowski said. I
interpret this as an observation of spontaneous regression, he
In melanoma, he said, it has been shown that spontaneous regression
is associated with an immune response, and in renal cancer, we
believe it to be the case, although we have not been able to prove it
to date, he commented.
Although T lymphocytes recognize and kill renal cancer cells, they
are present and active in only 20% to 25% of renal cancer patients.
Why arent they there in the other 75%? he asked.
It may be our inability to demonstrate their presence in the
lab, or they may not have developed, or there may be a negative
influence on their development.
Administration of cytokines to kidney cancer patients has, in some
cases, resulted in significant regression, which provides fuel for
the argument that they are involved in provoking the appropriate
The cytokines tested in kidney cancer are interleukins 1 through 4,
plus 6 and 12; the interferons; and the colony-stimulating factors
GM-CSF, M-CSF, and erythropoietin. Of these, IL-2 and interferon have
stood out, he said.
When they work, these agents may work by modulating immune
response, but they also may exert a direct antitumor effect, correct
an immune defect that may occur in cancer patients, affect blood
vessels, or all of these. They may also play different roles in
different cases, he said.
Many investigators continue to study various forms of interferon.
One in Great Britain compared interferon to the hormone
methoxyprogesterone acetate (MPA), which is used for supportive care,
and thus allowed a comparison of the cytokine to what amounted to no
treatment, Dr. Bukowski said.
In the treated group, median survival was 8.5 months vs 6 months in
the MPA group. One-year survival was 43% vs 31%. Although the
research suggests that interferon may be useful, its potential
benefits have to be weighed against its side effects, which varied
from individual to individual. These are the only data Im
aware of in which treatment for advanced metastatic kidney cancer
showed any improvement in survival, he said.
Dr. Bukowski suggested that the mixed performance of cytokines in
cancer treatment probably means that the immune system interactions
and other factors in the disease are stronger than the agents
activity. Nevertheless, he said, patients who do respond do so
He added that there is little evidence the responses are related to a
mind-body or placebo effect. The placebo effect may be active
in pain control and measures of functionality, but not in measures of
tumor regression, Dr. Bukowski said.