Abstract
Recent clinical studies have suggested that the combination of subcutaneous recombinant human interleukin 2 (rIL-2) and interferon alpha (rIFN-alpha) is especially promising in advanced renal cell carcinoma. We assessed the safety, activity and toxicity of home therapy with these two agents in 50 patients. Each treatment cycle consisted of a 2 day pulse phase, with 9 x 10(6) IU m-2 of rIL-2 being given subcutaneously every 12 h, followed by a 6 week maintenance phase during which rIL-2 1.8 x 10(6) IU m-2 was administered subcutaneously every 12 h on days 1-5 and rIFN-alpha 2b 5 x 10(6) IU m-2 once a day on days 1, 3 and 5. Objective responses (CR+PR) occurred in 9/50 (18%) patients, six of whom (12%) achieved a complete response. Disease stabilisation was observed in 17 cases (34%) and 18 patients progressed during therapy. In the other six cases, treatment was interrupted early for toxicity or patient refusal. One patient died of myocardial infarction during the second cycle. The overall median survival was 12 months. Home therapy with subcutaneous rIL-2 + rIFN-alpha 2b proved to be active, feasible and moderately toxic, but serious adverse events can sometimes occur.
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- Atzpodien J., Körfer A., Franks C. R., Poliwoda H., Kirchner H. Home therapy with recombinant interleukin-2 and interferon-alpha 2b in advanced human malignancies. Lancet. 1990 Jun 23;335(8704):1509–1512. doi: 10.1016/0140-6736(90)93039-r. [DOI] [PubMed] [Google Scholar]
- Atzpodien J., Lopez Hänninen E., Kirchner H., Bodenstein H., Pfreundschuh M., Rebmann U., Metzner B., Illiger H. J., Jakse G., Niesel T. Multiinstitutional home-therapy trial of recombinant human interleukin-2 and interferon alfa-2 in progressive metastatic renal cell carcinoma. J Clin Oncol. 1995 Feb;13(2):497–501. doi: 10.1200/JCO.1995.13.2.497. [DOI] [PubMed] [Google Scholar]
- Atzpodien J., Poliwoda H., Kirchner H. alpha-Interferon and interleukin-2 in renal cell carcinoma: studies in nonhospitalized patients. Semin Oncol. 1991 Oct;18(5 Suppl 7):108–112. [PubMed] [Google Scholar]
- Cameron R. B., McIntosh J. K., Rosenberg S. A. Synergistic antitumor effects of combination immunotherapy with recombinant interleukin-2 and a recombinant hybrid alpha-interferon in the treatment of established murine hepatic metastases. Cancer Res. 1988 Oct 15;48(20):5810–5817. [PubMed] [Google Scholar]
- Dekernion J. B., Ramming K. P., Smith R. B. The natural history of metastatic renal cell carcinoma: a computer analysis. J Urol. 1978 Aug;120(2):148–152. doi: 10.1016/s0022-5347(17)57082-2. [DOI] [PubMed] [Google Scholar]
- Fosså S. D., De Garis S. T. Further experience with recombinant interferon alfa-2a with vinblastine in metastatic renal cell carcinoma: a progress report. Int J Cancer Suppl. 1987;1:36–40. doi: 10.1002/ijc.2910390708. [DOI] [PubMed] [Google Scholar]
- Krown S. E. Interferon treatment of renal cell carcinoma. Current status and future prospects. Cancer. 1987 Feb 1;59(3 Suppl):647–651. doi: 10.1002/1097-0142(19870201)59:3+<647::aid-cncr2820591313>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
- Lafreniere R., Rosenberg S. A. Adoptive immunotherapy of murine hepatic metastases with lymphokine activated killer (LAK) cells and recombinant interleukin 2 (RIL 2) can mediate the regression of both immunogenic and nonimmunogenic sarcomas and an adenocarcinoma. J Immunol. 1985 Dec;135(6):4273–4280. [PubMed] [Google Scholar]
- Lee K. H., Talpaz M., Rothberg J. M., Murray J. L., Papadopoulos N., Plager C., Benjamin R., Levitt D., Gutterman J. Concomitant administration of recombinant human interleukin-2 and recombinant interferon alpha-2A in cancer patients: a phase I study. J Clin Oncol. 1989 Nov;7(11):1726–1732. doi: 10.1200/JCO.1989.7.11.1726. [DOI] [PubMed] [Google Scholar]
- Medeiros L. J., Gelb A. B., Weiss L. M. Renal cell carcinoma. Prognostic significance of morphologic parameters in 121 cases. Cancer. 1988 Apr 15;61(8):1639–1651. doi: 10.1002/1097-0142(19880415)61:8<1639::aid-cncr2820610823>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
- Miller A. B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207–214. doi: 10.1002/1097-0142(19810101)47:1<207::aid-cncr2820470134>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
- Palmer P. A., Atzpodien J., Philip T., Negrier S., Kirchner H., Von der Maase H., Geertsen P., Evers P., Loriaux E., Oskam R. A comparison of 2 modes of administration of recombinant interleukin-2: continuous intravenous infusion alone versus subcutaneous administration plus interferon alpha in patients with advanced renal cell carcinoma. Cancer Biother. 1993 Summer;8(2):123–136. doi: 10.1089/cbr.1993.8.123. [DOI] [PubMed] [Google Scholar]
- Palmer P. A., Vinke J., Philip T., Negrier S., Atzpodien J., Kirchner H., Oskam R., Franks C. R. Prognostic factors for survival in patients with advanced renal cell carcinoma treated with recombinant interleukin-2. Ann Oncol. 1992 Jun;3(6):475–480. doi: 10.1093/oxfordjournals.annonc.a058239. [DOI] [PubMed] [Google Scholar]
- Quesada J. R., Rios A., Swanson D., Trown P., Gutterman J. U. Antitumor activity of recombinant-derived interferon alpha in metastatic renal cell carcinoma. J Clin Oncol. 1985 Nov;3(11):1522–1528. doi: 10.1200/JCO.1985.3.11.1522. [DOI] [PubMed] [Google Scholar]
- Ratain M. J., Priest E. R., Janisch L., Vogelzang N. J. A phase I study of subcutaneous recombinant interleukin-2 and interferon alfa-2a. Cancer. 1993 Apr 1;71(7):2371–2376. doi: 10.1002/1097-0142(19930401)71:7<2371::aid-cncr2820710731>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
- Rosenberg S. A. Immunotherapy of patients with advanced cancer using interleukin-2 alone or in combination with lymphokine activated killer cells. Important Adv Oncol. 1988:217–257. [PubMed] [Google Scholar]
- Rosenberg S. A., Lotze M. T., Yang J. C., Linehan W. M., Seipp C., Calabro S., Karp S. E., Sherry R. M., Steinberg S., White D. E. Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer. J Clin Oncol. 1989 Dec;7(12):1863–1874. doi: 10.1200/JCO.1989.7.12.1863. [DOI] [PubMed] [Google Scholar]
- Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1–10. doi: 10.1016/0197-2456(89)90015-9. [DOI] [PubMed] [Google Scholar]
- Vogelzang N. J., Lipton A., Figlin R. A. Subcutaneous interleukin-2 plus interferon alfa-2a in metastatic renal cancer: an outpatient multicenter trial. J Clin Oncol. 1993 Sep;11(9):1809–1816. doi: 10.1200/JCO.1993.11.9.1809. [DOI] [PubMed] [Google Scholar]
- Yang J. C., Topalian S. L., Parkinson D., Schwartzentruber D. J., Weber J. S., Ettinghausen S. E., White D. E., Steinberg S. M., Cole D. J., Kim H. I. Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report. J Clin Oncol. 1994 Aug;12(8):1572–1576. doi: 10.1200/JCO.1994.12.8.1572. [DOI] [PubMed] [Google Scholar]