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General considerations

Isolated in 1976, and known for its effects on activated T lymphocytes (hence the name T-Cell Growth Factor), Interleukin II is a cytokine synthesised by mononuclear blood cells.

It exerts numerous activities between the various populations of white blood cells (hence the name interleukin).

The development of a recombinant Interleukin II (Proleukin™), by genetic engineering, has allowed its use in human therapy.

Many studies have been performed in oncology, particularly in metastatic kidney cancer, for which we have almost no efficient therapy, but also for metastatic melanoma and various sarcomas, more or less insensitive to chemotherapy. Many of the initial promising and rapidly published results are nowadays debated.

In French pharmacopoeia, only the indication for metastatic kidney cancer remains.

Indications

Treatment of metastatic renal adenocarcinoma

It is generally acknowledged that patients should only be treated if they have no more than one or two poor prognosis factors, since only patients 'with good prognosis' (!) could possibly respond. These poor prognosis factors are:

• general status score >= 1, according to ECOG scale,
  
• metastases in more than one organ,
  
• an interval of less than 24 months between the initial diagnosis of primary tumour and the appearance of metastases.

Treatment administration

Many administration methods have been tested. The most frequent (since the best tolerated) is by subcutaneous injection. Very elaborate protocols have been set up, but generally a daily dose of 18 Million Units is recommended.

Objective response rates are between 15 and 30% (depending on publications), however, response is generally of short duration.

Complications

A the most frequently prescribed dosage

In almost every patient and at every cure, the following are observed: fever, more or less pruriginous skin rashes, flu-like syndrome, nausea, vomiting, diarrhoea. Generally, systemic administration of paracetamol, antidiarrhoeic and antiemetic as well as antihistaminic drugs is instituted.

The patient cannot work or undertake any significant daytime activity due to the flu-like syndrome.

More serious side effects have been observed:

There may be worsening of serous effusions, tendency to oedema with risk of general organic failure.

Due to this oedema, psychological disturbances are often observed with mental confusion, depression, light somnolence or coma. This treatment therefore has to be excluded in the case of brain metastases.

Worsening of previous bacterial infections may also occur.

A capillary loss syndrome has been described, particularly after intravenous infusion of the product. A loss of vascular tone is observed due to extravasation of plasma proteins and liquids in the extravascular space. General hypotension and organ hypoperfusion can be severe.

Doubts about the genuine indication

Due to these important side effects, in a pathology involving spontaneous rapid development, and due to the low number of truly enjoyable and lasting responses, many physicians doubt the genuine indications of Interleukin 2. The French Percy Quattro trial, presented by Dr Negrier et al at the 2005 ASCO meeting, demonstrated no benefit of Interleukin 2 (abstract LBA4511)

In an adjuvant setting, the German Cooperative Renal Carcinoma Chemo-Immunotherapy Trials Group (DGCIN) also recently published negative results.