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A phase-II study of low-dose cyclophosphamide and recombinant human interleukin-2 in metastatic renal cell carcinoma and malignant melanoma

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Summary

Recent preclinical and clinical studies that have demonstrated antitumor activity of high-dose recombinant interleukin-2 (rIL-2), and animal models that demonstrated a synergistic effect of low-dose cyclophosphamide, led us to study rIL-2 (Cetus Corp., Emeryville, Calif) in a phase II clinical trial in combination with low-dose cyclophosphamide in 32 patients, 18 with malignant melanoma and 14 with renal cell carcinoma. rIL-2 was given once daily at 3×106 U/m2, as a 30-min infusion for 14 days in cycle I and for 2×5 days in cycles II and III respectively; if tolerated, the dose was increased to a maximum of 6×106 U m−2 day−1; the cycles, separated by 1 week treatment-free intervals, were preceded each by a single i.v. bolus of cyclophosphamide at 350 mg/m2. The most prominent side-effects encountered in this trial consisted of a capillary leak syndrome, myalgia and fever that required dose reduction during the first cycle in one-half of the patients. Given the limit of tolerable toxicities in a standard care unit, the regimen employed achieved minor antitumor activity. No remission was achieved in patients with renal cell carcinoma, and 15% of melanoma patients showed objective responses (partial response + minor response).

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Authors and Affiliations

  1. Department of Hematology, University of Mainz, Langenbeckstr. 1, 6500, Mainz, Germany

    Albrecht Lindemann, Heinold Gamm, Wolfgang Oster, Markus Böhm, Friedhelm Herrmann & Roland H. Mertelsmann

  2. Department of Internal Medicine (Cancer Research), University of Essen, Germany

    Klaus Höffken, Otto Kloke & Jörg Hayungs

  3. Department of Immunology and Transfusion Medicine, University of Hannover, Germany

    Reinhold E. Schmidt

  4. Medical Department I, University of Köln, Germany

    Volker Diehl

  5. Hematology/Lymphoma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Jonathan E. Kolitz

  6. Cetus Corporation, EuroCetus, Amsterdam, The Netherlands

    Chris R. Franks

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  1. Albrecht Lindemann
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Lindemann, A., Höffken, K., Schmidt, R.E. et al. A phase-II study of low-dose cyclophosphamide and recombinant human interleukin-2 in metastatic renal cell carcinoma and malignant melanoma. Cancer Immunol Immunother 28, 275–281 (1989). https://doi.org/10.1007/BF00205237

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  • DOI: https://doi.org/10.1007/BF00205237

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