WASHINGTONEnough evidence has accumulated to suggest that
interleukin-12 [IL-12] deserves continued study in kidney cancer and
other malignancies, even though it has had a difficult track record
so far, Janice P. Dutcher, MD, said at the 1999 Kidney Cancer
Association Annual Convention. Dr. Dutcher is associate director for
clinical affairs, Our Lady of Mercy Cancer Center/New York Medical
While problems with dose and toxicity emerged in past clinical
studies of IL-12, researchers at Beth Israel Deaconess Hospital,
Boston, may have hit upon a useful balance by giving the drug twice a
week, Dr. Dutcher said.
Im not saying this is the answer to this disease,
she said. Im just saying it bothers me if we dont
fully explore every new drug that has a glimmer, because we need
anything we can find.
Researchers also need to explore every angle of a possible new drug
before they discard it from their candidate list, she said. The fact
that the immune systems role in kidney cancer is unclear has
not stopped scientists from investigating a number of
immunomodulators and their potential for treatment of the disease.
It is a lot of trial and error, Dr. Dutcher said.
Unfortunately, thats how weve made advances in
cancer. Nobody has waited to have the whole picture. Still, with a
little bit of theory and hypothesis and a lot of real hard work, we
have made steps forward by learning to control the immune system and
to activate the immune system.
A Rocky Path
Interleukin-12s rocky path in kidney cancer research began with
testing in mice showing the drug was extremely active, more so than
interleukin-2, Dr. Dutcher said. But in early testing, subcutaneous
and intravenous injection of IL-12 produced mouth sores, flu-like
symptoms, and elevated liver enzymes.
Later phase I studies, in which the dose was reduced, produced
responses in kidney cancer and melanoma, she said. In a phase
II study, doses were given over 5 days but the study was stopped
because of toxicitynevertheless, one patient had a partial
response lasting a year.
Other institutions gave IL-12 as a weekly dose, which caused
decreases in toxicity but no response. So whats in
between? Dr. Dutcher asked. Maybe twice a week. The
biology and pharmacology tell us that maybe twice a week dosing makes
Researchers are currently investigating IL-12 given on a twice-a-week
schedule for 6 to 18 months in Kaposis sarcoma in AIDS patients
and in cutaneous T-cell lymphoma, which is also associated with an
immune deficiency. So far, some of the patients are
experiencing a response to the drug, she said.
In the study of kidney cancer at Beth Israel Deaconess, the drug is
being given twice a week for 36 weeks or more. Patients are
tolerating the drug with only some minor side effects, Dr.
Dutcher said. Early results indicate the treatment is leading to
sustained gamma interferon levels, and some responses have been seen,
she said, emphasizing that these results are preliminary and have not
been published. The Boston team also plans other studies of the
cytokine, among them a trial of IL-12 in combination with IL-2.
The research results to date are sort of a wake-up call to you,
to me, to all of us, that we want to push further for this drug,
Dr. Dutcher concluded.