Denileukin diftitox

Denileukin diftitox is a combination of the active sections of interleukin 2 and diphtheria toxin. It binds to high-affinity interleukin 2 receptors on the cancer cell (and other cells), and the toxin portion of the molecule inhibits protein synthesis to result in cell death. The pharmacokinetics of denileukin diftitox are best described by a two-compartment model, with an a half-life of 2 to 5 minutes and a terminal half-life of 70 to 80 minutes. Denileukin diftitox is used for the treatment of persistent or recurrent cutaneous T-cell lymphoma whose cells express the CD25 receptor. Side effects include vascular leak syndrome, fevers/chills, hypersensitivity reactions, hypotension, anorexia, diarrhea, and nausea and vomiting. 

Denileukin diftitox (OltaxTM) Immunotoxin conjugate Relapsed / refractory cutaneous T-ceU lymphoma Phase II... 

Proleukin is a recombinant form of IL-2. It is approved for the treatment of malignant melanoma and renal cell cancer. Ontak (denileukin diftitox) is a fusion protein for the treatment of persistent or recurrent T-cell lymphoma. Activated T cells express lL-2 receptors. Ontak has a fragment that binds to the IL-2 receptor while the other part presents a diphtheria toxin to kill the activated T cell. 

Most patients using denileukin diftitox have flulike symptoms (fever, chills, myalgias, nausea, diarrhea) within a few hours to days of treatment. Another common adverse effect is an immediate hypersensitivity... 

Denileukin diftitox Cutaneous T cell lymphoma Phase II Phase III Ligands... 

Dosage form Ontak is supplied in single-use vials as a frozen solution for injection on thawing at room temperature or in a refrigerator. Each 2 ml vial of Ontak contains recombinant denileukin diftitox 300 pg. The thawed solution must not be refrozen. 

Clinical pharmacology Denileukin diftitox is a fusion protein designed to direct the cytocidal action of diphtheria toxin to cells that express the IL-2 receptor. It binds avidly to the high-affinity interleukin-2 receptor on target-cell surfaces, where it is... 

Pharmacokinetics Denileukin diftitox has a terminal half-life of 70 to 80 minutes, a volume of distribution ranging from 0.06 to 0.081iter/kg, and a total body clearance of 1 to 2ml/minper kg. Clearance rates have been significantly affected by the development of antibodies to denileukin diftitox, reducing mean systemic exposure by approximately 75%. 

A close relative of immunotoxins is the growth factor fusion toxin, in which antibody is replaced with a ligand or growth factor to provide selectively of the toxin domain in immunotoxin. One such molecule, containing human interleukin-2 (IL-2) fused to truncated diphtheria toxin (denileukin diftitox or Ontak), was approved by the FDA in 1999. 

Interferons and cytokines Denileukin diftitox, IL-2 Diphtheria conjugate Ontak 300 j,g in 2 ml IV infusion... 

Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneichematopoietic stem cell transplantation Ho,... 

Denileukin Diftitox. Denileukin Diftitox (Ontak) is formulated by combining interleukin-2 with diphtheria toxin.11 Certain leukemia and lymphoma cells have a surface receptor that has a high affinity for interleukin-2, thus attracting this drug directly to these cells. Upon binding with tbe receptor, the diphtheria toxin component of the drug inhibits cellular protein synthesis, which ultimately results in cell death. This... 

Denileukin Diftitox (Ontak] Cutaneous T-cell lymphomas Acute allergic reactions joint and muscle pain flulike symptoms infection Gl distress (nausea, vomiting, diarrhea]... 

Denileukin diftitox Ontak r Diphtheria toxin + IL-2 Fusion protein 2/5/1999... 

Ontak Denileukin diftitox Ligand Pharmaceuticals 2/1999 Persistant or recurrent cutaneous T-cell lymphoma E. coli... 

Interleukins andresleukin (IL-1), denileukin diftitox (fusion, protein-IL-2+ DT), anakinra (IL-2)... 

Denileukin diftitox Ontak (Ligand) Cutaneous T-cell lymphoma... 

In 71 patients with cutaneous T cell lymphomas randomized to denileukin diftitox 9 or 18 pg/kg/day, flu-like and gastrointestinal symptoms were observed in 92%... 

A dose-escalation study in 35 patients with psoriasis confirmed that constitutional symptoms in response to denileukin diftitox were dose-related and less frequent at lower doses (below 5 micrograms/kg/day) (17). There was only one case of mild vascular leak syndrome. Skin reactions compatible with delayed hypersensitivity reactions were noted in three patients, including one case of exfoliative dermatitis. 

The more severe adverse effects of denileukin diftitox consisted of acute hypersensitivity reactions during or within 24 hours of infusion in 69% of patients, and a vascular leak syndrome in 27% of patients, which was severe in 6%. In contrast to acute hypersensitivity reactions, the vascular leak sjmdrome was typically delayed and occurred within the first 2 weeks of infusion (18). Whether this was due to a direct action of denileukin diftitox or to tumor lysis syndrome is unknown. 

Denileukin diftitox is indicated for the treatment of persistent or recuirent cutaneous T-cell lymphoma who.se malignant cells express the CD25 component of the IL-2 receptor. 

Denileukin diftitox is supplied as a frozen solution in water for injection. It should be stored at -I0°C or colder. It IS suggested that the vials be thawed in a refrigerator at 3 to xT for less than 24 hours or at nKini temperature for... 

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