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 treated.
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.”