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Immunotherapy of advanced renal cell cancer using subcutaneous recombinant interleukin-2 and interferon-α

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Summary

The combined administration of subcutaneous recombinant human interleukin-2 (rIL-2) and interferon-α (rIFN-α) was studied in a phase II trial on patients with advanced progressive renal cell cancer. Safety, tolerance and clinical response rate of this outpatient treatment protocol were assessed in 29 evaluable patients who received a total of 47 cycles, each consisting of s.c. rIL-2 at 14.4–18 million IU m−2day−1 on days 1 and 2, followed by 6 weeks of combined administration of s.c. rIL-2 at 3.6–4.8 million IU m−2 day−1 on 5 days a week, and s.c. rIFN-α at 3–6 million units m−2 three times weekly over a period of 6 consecutive weeks. In patients exhibiting stable or regressive disease upon combined IL-2 and rIFN-α, the therapy was continued. The overall response rate was 31% (95% confidence limits = 15%–51%), with 6 out of 29 patients achieving partial remission (PR, 21%) and 3 patients complete remission (CR, 10%). In addition, 12 patients presented with stable disease. The median duration of response was 8.5 months in PR and 19+ months in CR. Long-term treatment using this regimen was associated mainly with moderate (WHO grade I–II) toxicity including fevers, chills, malaise, nausea and/or vomiting, anorexia and transient local inflammation at the injection sites. No toxic deaths occurred. Altered thyroid function was observed in more than half the patients. The combination regimen resulted in a significant increase in peripheral blood eosinophils and natural killer cells (P<0.005). Up-on treatment, 14 patients developed non-neutralizing activity against rIL-2, and 2 of these developed specific neutralizing antibodies after consecutive cycles; no anti-rIFN-2b antibodies were detected. In summary, subcutaneous long-term outpatient treatment with low-dose rIL-2 and rIFN-α is feasible, with moderate toxicity, and results in an objective tumor response rate comparable to that obtained previously with high-dose rIL-2 i.v. regimens.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Hannover Medical School, Konstanty-Gutschow-Strasse 8, W-3000, Hannover 61, Federal Republic of Germany

    H. Kirchner, H. Poliwoda & J. Atzpodien

  2. Department of Urology, Hannover Medical School, Konstanty-Gutschow-Strasse 8, W-3000, Hannover 61, Federal Republic of Germany

    W. de Riese & E. Allhoff

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  1. H. Kirchner
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  2. W. de Riese
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  3. E. Allhoff
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  4. H. Poliwoda
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  5. J. Atzpodien
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Kirchner, H., de Riese, W., Allhoff, E. et al. Immunotherapy of advanced renal cell cancer using subcutaneous recombinant interleukin-2 and interferon-α. World J Urol 9, 219–222 (1991). https://doi.org/10.1007/BF00182844

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