Inhaled IL-2 Stabilizes Pulmonary Metastases of Renal Cell Cancer

SAN FRANCISCO—The search for less invasive and less toxic methods todeliver interleukin-2 (IL-2) has moved beyond injection. Edith Huland,MD, PhD, of the University Clinic Eppendorf, Hamburg, Germany, has beenusing a nebulizer to deliver IL-2 for six years.

Inhaled IL-2 effectively stabilizedor reduced pulmonary metastases of renal cell carcinomas in 70% of patients,Dr. Huland said at the Proleukin First International Congress, sponsoredby Chiron. She is head of Transplantation and Tumor Immunology, Departmentof Urology, at the Hamburg clinic.

Outpatient Therapy

Toxicity was so low that many patients were able to continue their normalemployment during the outpatient treatment. “IL-2 is toxic only when itis in the vascular system,” she said. “We decided to keep it out of theblood by finding some other route of administration.”

Earlier success infusing high-dose IL-2 directly into the bladder encouragedDr. Huland to try inhalation therapy. Using an ordinary nebulizer, patientsinhaled high doses of IL-2, either alone or in combination with low-dosesubcutaneous IL-2 or IL-2 plus interferon-alfa-2b (Intron A). Unlike manyIL-2 trials, Dr. Huland accepted all patients who applied, regardless oftheir functional status or disease stage.

The expected median survival time for her patient population was fivemonths; the actual median survival was 12 months. Pulmonary metastasesfrom primary renal cell cancer responded in 15% of patients for a medianof 16 months. Metastases were stabilized in 55% for a median of seven months.

When combined with low-dose subcutaneous injections, inhalation therapyalso produced responses in liver, bone, and other renal cell cancer metastases.

Dr. Huland reported that side effects from inhaled IL-2 were mild. Only16% of patients suffered grade 3 toxicity. After more than 800 months oftreatment, the most common complaint was a dry cough, which was easilytreated.

Quality of life for patients on inhalation IL-2 therapy was also muchimproved over other regimens, whether measured by physician-administeredinstruments or self-evaluation instruments. Results from self-administeredEORTC questionnaires showed a 15% decline in quality of life during inhalationtherapy. Intravenous high-dose IL-2 typically produces a 70% decline inquality of life as measured by the same instrument, Dr. Huland noted.

The extremely low incidence of toxicity and the high proportion of partialresponders to inhaled IL-2 also shifts the focus of treatment from completeremission 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.”