Abstract
During this phase I/II study, enodolymphatic cannulae were placed in the iliac lymphatics under general anaesthesia. IL2 was then infused via this route at escalating doses until the highest tolerated dose was achieved; then, continuous infusion was maintained for 2 to 3 weeks. Seven patients with advanced cancer (3 lymphoma, 4 melanoma), resistant to all other modalities of treatment received such therapy.
Most patients tolerated 4 to 5 × 106 u/day of IL2 for 2 to 3 weeks with less toxicity as compared to the equivalent dosage given intravenously. No severe perioperative morbidity was experienced. One melanoma patient had a minor clinical response. Changes in circulating lymphocyte numbers and cytotoxicity demonstrated a systemic effect of endolymphatic IL2 therapy.
Conclusions: The endolymphatic administration of IL2 is associated with less toxicity than the intravenous route but still achieves a systemic effect; a lower tumour burden may prove more responsive to this therapy.
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References
Winkelhake JL, & Gauny SS. Human recombinant interleukin-2 as an experimental therapeutic. Pharm Rev 1990; 42: 1–28.
Rosenberg SA, Lotze MT, Muul LM, et al. Experience with the use of high dose Interleukin-2 in the treatment of 652 cancer patients. Ann Surg 1989; 210: 474–85.
Forni G, Grovarelli M, Santoni A, Modesti A, Forni M. Tumour inhibition by IL2 at the tumour/host interface. Biochem et Biophys Acta 1986; 865: 307–28.
Thatcher N, Dazzi H, Gosh A, Johnson RJ. Recombinant IL-2 given intravenously in advanced malignant melanoma: a phase 1/11 study. Cancer Treat Rev 1989; 16 (supp 1A): 49–52.
Malkovksy M, Sondel PM. Interleukin 2 and its receptor structure, function and therapeutic potential. Blood Rev 1987; 1: 254–66.
Aroussan FR, Libby P, Brandom EP, et al. IL-2 rapidly induces natural killer cell adhesion to human endothelial cells. J Immunol 1988; 141: 158–63.
Gottleib DJ, Prentice ITG, Heslop HE, et al. Effects of recombinant IL2 administration on cytotoxic function following high dose chemo-radiotherapy for haematological malignancy. Blood 1989; 74: 2335–42.
Hank JA, Kohler PC, Weil-Hillman G, et al.In vivo induction of the LAK phenomenon: IL2 dependent human non-major histocompatibility complex-restricted cytotoxicity generatedin vivo during administration of human recombinant IL2. Can Res 1988; 48: 1965–71.
Lotze MT, Matory YL, Ettinghausen SE, et al.In vivo administration of purified human IL2: half life immunologic effects and expansion of peripheral lymphoid cellsin vivo with IL2. J Immunol 1985; 135: 2866–75.
Fische P, Malkovsky M, Braakman E, et al.γ/δ cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatabilty complex-restricted cytolysis. J Exp Med 1991; 171: 1567–79.
Rees RC, Wiltrout RH. The biology and clinical application of IL 2 Immunol Today 1991; 11: 36–8.
Pichert G, Jost LM, Fierz W, Stahel RA. Clinical and immune modulatory effects of alternative weekly IL2 and interferon in patients with advanced renal cell carcinoma and melanoma. Br J Cancer 1991; 63: 287–92
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Galvani, D.W., Walton, I.S., Davies, J.M. et al. Endolymphatic delivery of IL2 in patients with melanoma and lymphoma. Biotherapy 4, 251–255 (1992). https://doi.org/10.1007/BF02172654
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DOI: https://doi.org/10.1007/BF02172654