Denileukin diftitox.
Denileukin diftitox is a novel interleukin-2 receptor (IL-2R)-targeted diphtheria toxin. It binds to cells expressing IL-2R and inhibits protein synthesis through internalization of the diphtheria toxin fragment. In patients with IL-2R-positive cutaneous T cell lymphoma (CTCL), the overall response rate was 23 and 36%, respectively, after denileukin diftitox 9 or 18 micrograms/kg/day for 5 days every 3 weeks and was 37% in a dose-ranging trial. Quality of life (QOL) improved significantly in patients with CTCL who responded to treatment with denileukin diftitox 9 or 18 micrograms/kg/day compared with QOL at baseline and in nonresponders. In a murine model of IL-2R-expressing malignancy, denileukin diftitox prolonged survival compared with controls. The most common adverse events reported in patients who received denileukin diftitox were hypoalbuminemia, fever/chills, acute hypersensitivity reactions, nausea/vomiting and asthenia. Vascular leak syndrome has occurred during denileukin diftitox therapy. Antibody titers to denileukin diftitox occur in most patients after treatment but the presence of antibodies does not preclude a clinical response.
Figgitt
D P
DP
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Lamb
H M
HM
Goa
K L
KL
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004167:Diphtheria Toxin / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology* / Q000627:therapeutic use*; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology* / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox