Aldesleukin

Aldesleukin is indicated for the treatment of metastatic renal cell carcinoma.

Risk factors associated with decreased response rates and median survival are:

• A performance status of ECOG* 1 or greater
• More than one organ with metastatic disease sites
• A period of <24 months between initial diagnosis of primary tumour and the date the patient is evaluated for aldesleukin treatment.

* ECOG (Eastern Cooperative Oncology Group) 0 = normal activity, 1 = symptoms but ambulatory; 2 = in bed less than 50% of time; 3 = in bed more than 50% of time.

Response rates and median survival decrease with the number of risk factors present. Patients positive for all three risk factors should not be treated with aldesleukin.

Aldesleukin therapy is contra-indicated in patients who are likely to require corticosteroids.

Aldesleukin therapy is contra-indicated in patients with evidence of active infection requiring antibiotic therapy.

Aldesleukin therapy is contra-indicated in patients with patients with a significant history or current evidence of severe cardiac disease. In questionable cases a stress test should be performed.

Use of contrast media after aldesleukin administration may result in a recall of the toxicity observed during aldesleukin administration. Most events were reported to occur within 2 weeks after the last dose of aldesleukin, but some occurred months later. Therefore it is recommended not to use contrast media within 2 weeks after treatment with aldesleukin.

Aldesleukin administration should be discontinued in patients developing severe lethargy or somnolence; continued administration may result in coma.

Aldesleukin causes adverse events that affect the ability to drive and operate machines. Patients should not drive or operate machines until they have recovered from the undesirable effects.

It is not known whether this drug is excreted in human milk. Because the potential for serious adverse reactions in nursing infants is unknown, mothers should not breast feed their infants during treatment.

There are no adequate data on the use of aldesleukin in pregnant women. Experimental animal studies are insufficient to assess the safety with respect to reproduction, development of the embryo or foetus, the course of gestation and peri- and postnatal development. Proleukin has been shown to have embryolethal and maternal toxic effects in rats. The potential risk for humans is unknown. Proleukin should not be used during pregnancy unless the potential benefit to the patient justifies the potential risk to the foetus.

Fatal Tumour Lysis Syndrome has been reported in combination of aldesleukin with treatment with cis-platinum, vinblastine and dacarbazine. Concomitant use of the mentioned active substances is therefore not recommended.

There has also been exacerbation or the initial presentation of a number of autoimmune and inflammatory disorders observed following concurrent use of interferon-alpha and aldesleukin, including crescentic immunoglobulin A (IgA) glomerulonephritis, oculo-bulbar myasthenia gravis, inflammatory arthritis, thyroiditis, bullous pemphigoid, and Stevens-Johnson syndrome. It is recommended that patients with pre-existing auto-immune disease should not be treated with aldesleukin.

Severe rhabdomyolysis and myocardial injury, including myocardial infarction, myocarditis and ventricular hypokinesia appear to be increased in patients receiving aldesleukin (intravenously) and interferon-alpha concurrently.

Aldesleukin therapy is contra-indicated in patients with serum creatinine outside normal range.

Aldesleukin therapy is contra-indicated in patients with pre-existing severe major organ dysfunction.

Aldesleukin therapy is contra-indicated in patients with (Central Nervous System) CNS metastases or seizure disorders, with the exception of patients with successfully treated brain metastases (negative computerized tomography (CT); neurologically stable).

Aldesleukin therapy is contra-indicated in patients with a PaO₂ <60 mmHg during rest.

Aldesleukin therapy is contra-indicated in patients with a performance status of ECOG ≥2.

Aldesleukin therapy is contra-indicated in patients with serum bilirubin outside normal range.

Aldesleukin therapy is contra-indicated in patients with organ allografts.

Aldesleukin therapy is contra-indicated in patients with pre-existing auto-immune disease.