Background: To confirm the usefulness of a combination therapy of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) against metastatic renal cell carcinoma, the recommended dose of IFN-alpha to use in combination with low-dose IL-2 was determined (phase 1). Efficacy and safety at this dose was evaluated (phase 2).
Methods: In phase 1, the dose of IL-2 was fixed at 0.7 x 10(6) Japan reference unit (JRU)/person for 5 days a week. The dose of IFN-alpha was increased from 3 x 10(6) IU for 3 days a week (level I) to 6 x 10(6) IU for 3 days a week (level II) and to 6 x 10(6) IU for 5 days a week (level III).
Results: In phase 1, 10 patients were registered, with 9 (3 at each level) able to be evaluated. Because grade 3 and grade 4 neutropenia were observed at level III in 1 patient each, level II was found to be the recommended regimen. The response rate in phase 1 was 44.4% (4/9). In phase 2, 46 patients were registered, with a response rate in 37 patients, classified as per protocol set (PPS), of 21.6% (8/37). Toxicities observed were primarily flu-like symptoms due to cytokines, and gastrointestinal symptoms. Leukocyte abnormalities were observed, but they were milder and tolerable.
Conclusion: In the 46 patients evaluated in phase 1 and phase 2, the response rate was 26.1% (12/46), being highest in 38.7% (12/31) of those who were nephrectomized, and with only lung metastases.