SAN FRANCISCOAn outpatient combination of low-dose interleukin-2 (IL-2, Proleukin), interferon alfa-2b(Drug information on interferon alfa-2b) (Intron A), and fluorouracil(Drug information on fluorouracil) appears to offer response and survival rates similar to high-dose IL-2 with minimal side effects, according to studies conducted by Jens Atzpodien, MD, associate professor of medicine, Medizinische Hochschule, Hannover, Germany.
We can dramatically reduce the systemic toxicity and keep patients out of the hospital with this regimen, Dr. Atzpodien said at the Proleukin First International Congress, sponsored by Chiron. We see a better quality of life, at least for complete responders and probably for all patients.
Dr. Atzpodien began trying to move IL-2 into the outpatient setting soon after he began working with the drug in 1988. In the current regimen, evaluated in a phase II renal cell carcinoma trial, patients receive up to four cycles, unless their disease progresses, of the following:
- Subcutaneous IL-2, 10 million IU/m² twice daily on days 3, 4, and 5 of weeks 1 and 4; and 5 million IU/m² on days 1, 3, and 5 of weeks 2 and 3.
- Subcutaneous interferon-alfa-2b, 6 million IU/m² on day 1 of weeks 1 and 4 and on days 1, 3, and 5 of weeks 2 and 3; and 9 million IU/m² once weekly on weeks 5 to 8.
- Fluorouracil by intravenous bolus injection, 1,000 mg/m² once weekly on weeks 5 to 8.
The response rates, he said are quite similar to what has been achieved with high-dose IL-2 regimens. Complete remissions were seen in 10% of patients and partial responses in 20.5%.
Median survival was 21 months for all patients and 50 months for those in the lowest risk group. The five-year survival probability was 13% for all patients, with half of all complete responders still alive five years after treatment. The investigators have confirmed the results in a prospectively randomized trial.
Toxicities were primarily grade 1 and 2, with a few grade 3 adverse effects and no grade 4 effects; fewer than 3% of patients required even minimal inpatient treatment. None of the 243 patients in the study required IV pressors.
Like other researchers, Dr. Atzpodien found a distinct subgroup of complete responders who were much more responsive to treatment than were other patients in the study.
Patients who develop thyroid autoantibodies showed a significantly higher five-year survival rate than other patients, he reported, but the connection, if there is one, between thyroid antibodies and survival remains unclear.