SAN FRANCISCOThe search for less invasive and less toxic methods to
deliver interleukin-2 (IL-2) has moved beyond injection. Edith Huland,
MD, PhD, of the University Clinic Eppendorf, Hamburg, Germany, has been
using a nebulizer to deliver IL-2 for six years.
Inhaled IL-2 effectively stabilized
or reduced pulmonary metastases of renal cell carcinomas in 70% of patients,
Dr. Huland said at the Proleukin First International Congress, sponsored
by Chiron. She is head of Transplantation and Tumor Immunology, Department
of Urology, at the Hamburg clinic.
Toxicity was so low that many patients were able to continue their normal
employment during the outpatient treatment. “IL-2 is toxic only when it
is in the vascular system,” she said. “We decided to keep it out of the
blood by finding some other route of administration.”
Earlier success infusing high-dose IL-2 directly into the bladder encouraged
Dr. Huland to try inhalation therapy. Using an ordinary nebulizer, patients
inhaled high doses of IL-2, either alone or in combination with low-dose
subcutaneous IL-2 or IL-2 plus interferon-alfa-2b (Intron A). Unlike many
IL-2 trials, Dr. Huland accepted all patients who applied, regardless of
their functional status or disease stage.
The expected median survival time for her patient population was five
months; the actual median survival was 12 months. Pulmonary metastases
from primary renal cell cancer responded in 15% of patients for a median
of 16 months. Metastases were stabilized in 55% for a median of seven months.
When combined with low-dose subcutaneous injections, inhalation therapy
also produced responses in liver, bone, and other renal cell cancer metastases.
Dr. Huland reported that side effects from inhaled IL-2 were mild. Only
16% of patients suffered grade 3 toxicity. After more than 800 months of
treatment, the most common complaint was a dry cough, which was easily
Quality of life for patients on inhalation IL-2 therapy was also much
improved over other regimens, whether measured by physician-administered
instruments or self-evaluation instruments. Results from self-administered
EORTC questionnaires showed a 15% decline in quality of life during inhalation
therapy. Intravenous high-dose IL-2 typically produces a 70% decline in
quality of life as measured by the same instrument, Dr. Huland noted.
The extremely low incidence of toxicity and the high proportion of partial
responders to inhaled IL-2 also shifts the focus of treatment from complete
remission to longer term stability.
“We are seeing that long-term therapy with inhaled IL-2 is possible,”
Dr. Huland commented. “At the very least, we can stabilize these patients,
some of them for several years.”