Uses
Antineoplastic;
biological response modifier; immunostimulant.
Indications
Aldesleukin (IL-2, Proleukin) is a human recombinant
interleukin-2 protein. Its antitumor action is thought to
include multiple effects on the immune system, such as
enhancement of T-lymphocyte cytotoxicity, induction of
natural killer cell activity, and induction of interferon-γ
production. Aldesleukin has been used alone and in
combination with lymphokine activated killer (LAK)
cells or tumor-infiltrating lymphocytes (TIL).
The drug produces remissions in 15% of patients
with renal cell carcinoma, with median durations of remission
of 18 to 24 months.
Brand name
Proleukin (Chiron).
General Description
Aldesleukin, interleukin-2 (Proleukin),is an rDNA-derived lymphokine that differs structurallyfrom native interleukin-2 (IL-2) but has biological activitysimilar to that of the natural lymphokine. Natural IL-2 isproduced primarily by the peripheral blood lymphocytesand contains 133 amino acid residues. The immunoregulatoryeffects of aldesleukin include enhancing mitogenesis oflymphocytes, stimulating the growth of IL-2–dependentcell lines, enhancing cytotoxicity of lymphocytes, inducinglymphokine-activated killer (LAK) cells and NK cells, andinducing interferon- production. The exact mechanism ofthe antitumor activity of aldesleukin in humans is unknown.The primary indication for aldesleukin is in the treatmentof adult metastatic renal carcinoma.
General Description
Aldesleukin, T-cell growth factor, thymocyte-stimulatingfactor, Proleukin, is recombinant IL-2 expressed in an engineeredstrain of E. coli containing an analog of the humanIL-2 gene.Aldesleukin enhances lymphocyte mitogenesis and stimulateslong-term growth of human IL-2-dependent cell lines.
IL-2 also enhances the cytotoxicity of lymphocytes. Inductionof NK cell and lymphocyte-activated killer (LAK) cell activityoccurs, as does induction of production. In mouse andhuman tumor cell lines, aldesleukin activates cellular immunityin patients with profound lymphocytosis, eosinophilia,and thrombocytopenia. Aldesleukin also activates the productionof cytokines, including tumor necrosis factor (TNF),IL-1, and IFN-γ. In vivo experiments in mouse tumor modelshave shown inhibition of tumor growth. The mechanism ofthe antitumor effect of aldesleukin is unknown.
Aldesleukin is indicated for the treatment of metastaticrenal cell carcinoma in adults. It is also indicated for thetreatment of metastatic melanoma in adults. Research isunder way on the use of aldesleukin for the treatment of variouscancers (including head and neck cancers), treatment ofacute myelogenous leukemia, and adjunct therapy in thetreatment of Kaposi sarcoma. Renal and hepatic function istypically impaired during therapy with aldesleukin, so interactionwith other drugs that undergo elimination by these organsis possible.
Side effects
Several serious toxicities have been observed, with a
fatality rate of 5% in the initial studies. The major adverse
effect is severe hypotension in as many as 85% of
patients, which may lead to myocardial infarctions, pulmonary
edema, and strokes.This hypotension is thought
to be due to a capillary leak syndrome resulting from
extravasation of plasma proteins and fluid into extravascular
space and a loss of vascular tone. Patients
with significant cardiac, pulmonary, renal, hepatic, or
CNS conditions should not receive therapy with
aldesleukin. Other adverse reactions include nausea
and vomiting, diarrhea, stomatitis, anorexia, altered
mental status, fevers, and fatigue.
