Toxicity management in patients receiving low-dose aldesleukin therapy.
OBJECTIVE
To review the pathophysiology and subsequent treatment options for low-dose aldesleukin-induced toxicity when administered via intravenous bolus infusion, continuous intravenous infusion, or subcutaneous injection.


BACKGROUND
The adverse events associated with high-dose aldesleukin therapy (600,000 IU per kg i.v. every 8 h for a maximum of 14 doses) are well documented in the literature; however, the adverse event profile of lower doses and alternative administration routes are less well described. An understanding of the adverse event profile associated with these alternative regimens can enhance management of toxicity.


METHODS
English-language clinical studies, abstracts, and review articles pertaining to low-dose intravenous, continuous intravenous infusion, or subcutaneous injection of aldesleukin, as well as aldesleukin-induced adverse events.


METHODS
Relevant studies were selected that assist with understanding the pathophysiology, clinical management, diagnosis, and management of aldesleukin-induced adverse events.


CONCLUSIONS
Aldesleukin therapy initiates a cytokine-mediated proinflammatory process resulting in a toxicity profile that is different from traditional nonbiologic chemotherapeutic agents. The frequency and severity of adverse events associated with aldesleukin administration are dependent upon dose, route, and administration schedule. In addition, most adverse reactions are self-limiting. Alleviation of aldesleukin-induced adverse effects can usually be achieved on an outpatient basis with agents such as antiemetics, antipyretics, and topical creams or lotions, as well as nonmedication interventions. Aggressive and proactive management of aldesleukin associated toxicities can help facilitate completion of therapy.
Sundin
D J
DJ
Medical Affairs Department, Chiron Therapeutics, Emeryville, CA 94608, USA. david_sundin@cc.chiron.com
Wolin
M J
MJ
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016207:Cytokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010353:Patient Education as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects
D000970:Antineoplastic Agents; D016207:Cytokines; D007376:Interleukin-2; D011994:Recombinant Proteins; C082598:aldesleukin