Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Proleukin (CSL)
vials containing 18 million IU as powder
Approved indication: renal cell carcinoma
Australian Medicines Handbook Section 14.2
Renal cell carcinoma is increasing in incidence. Many patients present with metastases and have a poor prognosis. Chemotherapy does not improve survival. In some patients the cancer may spontaneously regress suggesting an immune response. This has prompted research into the role immunomodulators, such as interferon, could play in treatment.
Aldesleukin is a recombinant form of the cytokine interleukin 2. This cytokine stimulates the production of killer cells and enhances the cytotoxicity of lymphocytes. It is also involved in the production of interferon and tumour necrosis factor.
A randomised trial compared aldesleukin, interferon alpha-2a or a combination of both treatments in 425 patients with progressive metastatic renal cell carcinoma. The response to treatment was assessed using CT scans to measure the regression of the tumour. After 10 weeks 6.5% (9/138) of patients given aldesleukin had responded. The response rate at 25 weeks was 2.9%. Patients who received the two treatments in combination had significantly higher response rates (18.6% at 10 weeks, 13.6% at 25 weeks).1
Aldesleukin given intravenously has many adverse effects, so it has only been approved for subcutaneous injection.
This requires daily injections for five days a week for four weeks. After four weeks the patient has one week's rest and then the cycle is repeated.
The subcutaneous injection has a bioavailability of 35-47%. It is metabolised and excreted by the kidneys with a half-life of 5-9 hours.
In studies involving a total of 103 patients, subcutaneous injections produced a complete response in four patients. The overall response rate was 14%.
Most patients will develop adverse reactions to aldesleukin, chills and fever being particularly common. Approximately 12% of patients develop hypotension. This may be part of a 'capillary leak syndrome' which also includes oliguria, pulmonary oedema and weight gain. More than half the patients will become anaemic or have altered liver function. Patients may develop antibodies to aldesleukin and some of the antibodies will have neutralising activity. Autoimmune and inflammatory diseases may flare up during treatment.
Aldesleukin does not increase survival. In the comparative study median survival was only 12 months.1 However, the studies of subcutaneous aldesleukin showed that the response was prolonged in the few patients who had a complete response. The median response duration was 64 months. Further studies are needed to identify which factors predict a favourable response.
