Imatinib

Synonyms:STI-571, imatinib mesylate

Imatinib is a cancer chemotherapeutic agent which inhibits the enzyme protein-tyrosine kinase. The introduction of imatinib has revolutionized the treatment of chronic myeloid leukaemia (CML).^1,2 It is also licensed for Kit-positive unresectable or metastatic gastrointestinal stromal tumours (GIST).^3,4

Imatinib competitively inhibits the enzyme tyrosine kinase at the enzyme's ATP-binding site. This inhibits the tyrosine kinase involved in the Philadelphia chromosome abnormality of chronic myeloid leukaemia (BCR-ABL tyrosine kinase) but also inhibits tyrosine kinases for platelet-derived growth factor and c-Kit (a stem cell factor).⁵ The enzyme inhibition inhibits growth and causes apotosis.

• Primary uses:
  • Chronic myeloid leukaemia (CML)
  • Sarcoma, gastrointestinal stromal tumour (GIST)
• Other uses:
  • Acute leukaemias which are Philadelphia chromosome positive (unlicensed indication).
  • In October 2003 NICE recommended imatinib as first line treatment for Philadelphia-chromosome-positive CML in the chronic phase and in the accelerated phase or with blast crisis if not used previously. Use beyond this is only recommended as part of a clinical study.⁶ Review of this guidance has been deferred until 2009 awaiting trial results and reports.
  • In October 2004 NICE made recommendations on the use of imatinib with GIST tumours. It was recommended that imatinib be used for such tumours if KIT-positive unresectable or that have spread to other parts of the body (The treatment is given for 12 weeks and then only continued if the tumour is shown to respond to treatment).⁷

Imatinib should only be initiated in specialist centres. It is given orally and is metabolised mainly in the liver. Peak plasma concentrations are reached at between 2-4 hours and it is excreted mostly in faeces with a half life of 18 hours. Many dosage schedules exist according to disease, response and concomitant therapy.

These include haematological effects (mainly anaemia, neutropenia and thrombocytopenia) gastrointestinal effects and constitutional upset. The bone marrow suppression is dose related and can usually be managed with dose reduction.

The use of shared care protocols should be facilitated and encouraged.
These should include monitoring of the disease and incorporate monitoring of full blood count, liver function (for hepatotoxicity) and possible side effects.

Grapefruit juice should be avoided (As should rifampicin, simvastatin, paracetamol and warfarin).