Interferon-alpha

Interferons are naturally occurring proteins produced by animal cells in response to multiple stimuli. Based on their structural and functional characteristics, they are divided into interferons-alpha, -beta, and -gamma. However, only IFN-α has shown appreciable activity in haematological malignancies. There are two forms of IFN-α , IFN-α 2-a (Roferon-A®, Roche) and IFN-α 2-b (Intron-A®, Schering), that are widely used to treat CML (chronic myeloid leukaemia).

 

  • The molecular and biological mechanisms of action of the IFNs are poorly understood. They may have direct anti-tumour effects, but they may also have effects on the immune system.
  • IFN-α has been shown to be clearly superior to standard chemotherapy for the treatment of CML.
  • A recent meta-analysis of seven randomised trials confirmed better 5-year survival rates with IFN-α than with either hydroxyurea or busulfan (CML Trialists’ Collaborative Group 1997).
  • IFN-α is the first-line therapy for patients with CML in chronic phase who are not candidates for SCT (stem cell transplantation).
  • IFN-α produces a CHR in a substantial number of patients and a cytogenetic remission in many, with complete or partial cytogenetic response (major cytogenetic response) rates in the range of 20%–30%. Five to ten percent of patients have the sustained disappearance of all Ph+ cells
  • Doses of IFN-α in clinical trials have ranged from 2 to 5 million IU/m2. The current standard dose is 5 million IU/m2, or the maximum tolerated dose up to this level, given daily by subcutaneous injection.
  • The optimal duration of therapy with IFN-α is not known. If there is no evidence of a cytogenetic response by 12 months, other therapies, including SCT, should be considered. However, if a cytogenetic response is achieved, treatment is often continued for at least 2 years or until a complete cytogenetic response has been documented by FISH.
  • IFN-α has recently been combined with low-dose cytosine arabinoside (Ara-C, cytarabine, Cytosar-U®, Pharmacia) for the treatment of CML. Studies have demonstrated higher response rates with this combination than with IFN-α alone, and it is being increasingly used in larger centres.
  • More than 90% of patients on IFN-α will experience side-effects. These require dose reduction in more than 50% of patients and discontinuation of treatment in up to 20%. A patient whose IFN-α treatment is discontinued due to severity of side-effects is called interferon-intolerant.

Management of IFN-α –related toxicities is symptomatic. Common side-effects include:

 

  • Fever and chills
  • Anorexia
  • Post-nasal drip
  • Fatigue
  • Depression
  • Weight loss
  • Peripheral neuropathy