Abstract
It has been postulated that favouring the absorption of interleukin-2 via lymphatics rather than venous capillaries after subcutaneous adminstration may improve its therapeutic index. We have now evaluated in 12 cancer patients the plasma pharmacokinetic of interleukin-2 either dissolved in water or in 20% albumin solution with an internal cross-over after at least three days. Our data show that when albumin is present, the plasma concentrations of interleukin-2 versus time is increased and swelling at the injection sites is reduced. It remains to be seen whether efficacy improves during a prolonged treatment.
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Abbreviations
- AUC:
-
Area Under Plasma Curve
- BRM:
-
Biological Response Modifiers
- IFN:
-
Interferon
- IL-2:
-
Interleukin-2
- IV:
-
Intravenous
- SC:
-
Subcutaneous
- MU:
-
Megaunit
References
Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT, Seipp CA, Simpson CG, White DE. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. New Engl J Med 1987; 316: 889–97.
West WH, Tauer KW, Yannelli JR, Marshall GD, Orr DW, Thurman GB, Oldham RK. Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. New Engl J Med 1987; 316: 898–905.
Sarna GP, Figlin RA, Pertcheck M, Altrock B, Kradjian SA. Systemic administration of recombinant methionyl human interleukin-2 (Ala 125) to cancer patients: clinical results. J Biol Resp Modif 1989; 8: 16–24.
Thompson JA, Lee DJ, Cox WW, Lindgren CG, Collins C, Neraas KA, Dennin RA, Fefer A. Recombinant interleukin 2 toxicity, pharmacokinetics, and immunomodulatory effects in a phase I trial. Cancer Res 1987; 47: 4202–7.
Whitehead RP, Ward D, Hemingway L, Hemstreet GP III, Bradley E, Konrad M. Subcutaneous recombinant interleukin-2 in a dose escalating regimen in patients with metastatic renal cell adenocarcinoma. Cancer Res 1990; 50: 6708–15.
Atzpodien J, Körfer A, Franks CR, Poliwoda H, Kirchner H. Home therapy with recombinant interleukin-2 and interferon-α2b in advanced human malignancies. Lancet 1990; 335: 1509–12.
Stein RC, Malkovska V, Morgan S, Galazka A, Aniszewski C, Roy SE, Shearer RJ, Marsden RA, Bevan D, Gordon-Smith EC, Coombes RC. The clinical effects of prolonged treatment of patients with advanced cancer with low-dose subcutaneous interleukin-2. Brit J Cancer 1991; 63: 275–8.
Bocci V. Distribution, catabolism and pharmacokinetics of interferons. In: Finter NB, Oldham RK, eds. Interferon, Vol. 4:in vivo and clinical studies. Elsevier Science Publishers BV, 1985: 47–72.
Bocci V, Pessina GP, Paulesu L, Nicoletti C. The lymphatic route. VI. Distribution of recombinant interferon-α2 in rabbit and pig plasma and lymph. J Biol Resp Modif 1988; 7: 390–400.
Bocci V, Pessina GP, Nicoletti C, Paulesu L. The lymphatic route. VII. Distribution of recombinant human interleukin-2 in rabbit plasma and lymph. J Biol Regul Homeost Agents 1990; 4: 25–9.
Berman M, Weiss MF. SAAM 27. Bethesda, Maryland: National Institute of Health, 1977.
Bocci V. Metabolism of protein anticancer agents. Pharm Ther 1987; 34: 1–49.
Bocci V. Evaluation of routes of administration of interferon in cancer: a review and a proposal. Cancer Drug Del 1984; 1: 337–51.
Oldham RK. Biological response modifiers program. J Biol Resp Modif 1982; 1: 81–100.
Donohue JH, Rosenberg SA. The fate of interleukin-2 afterin vivo adminstration. J Immunol 1983; 130: 2203–8.
Bocci V. Interleukins. Clinical pharmacokinetics and practical implications. Clin Pharmacokinet 1991; 21: 274–84.
Sulis E, Floris C, Massidda C. Intralymphatic infusion of interferon in patients with lymph nodal metastases from melanoma of the lower limbs. Cancer Chemother Pharmacol 1989; 24: 393–4.
Shau H, Isacescu V, Ibayashi Y, Tokuda Y, Golub SH, Fahey JL, Sarna GP. A pilot study of intralymphtic interleukin-2. I. Cytotoxic and surface marker changes of peripheral blood lymphocytes. J Biol Resp Modif 1990; 9: 71–80.
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Bocci, V., Carraro, F., Zeuli, M. et al. The lymphatic route. VIII. Distribution and plasma clearance of recombinant human interleukin-2 after SC administration with albumin in patients. Biotherapy 6, 73–77 (1993). https://doi.org/10.1007/BF01877388
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DOI: https://doi.org/10.1007/BF01877388