Europe: Sprycel for treatment-resistant chronic myeloid leukaemia and Ph+ acute lymphoblastic leukaemia
The European Commission approved Sprycel ( Dasatinib ) for the treatment of adults with chronic, accelerated or blast phase chronic myeloid leukaemia with resistance or intolerance to prior therapy, including Imatinib ( Glivec / Gleevec ).
Sprycel is also indicated for the treatment of adults with Philadelphia chromosome positive ( Ph+ ) acute lymphoblastic leukaemia and lymphoid blast chronic myeloid leukaemia with resistance or intolerance to prior therapy.
For patients with chronic myeloid leukaemia or Ph+ acute lymphoblastic leukaemia, the development of resistance or intolerance to standard treatment can be a devastating event. The potential for drug resistance to develop may increase with length of prior treatment and the stage of disease.
Emerging evidence from a single European centre study indicates that resistance to Imatinib may occur in approximately 25% of chronic phase chronic myeloid leukaemia patients, 41% of accelerated phase patients and 92% of blast crisis patients.
Resistance to therapy is thought to involve the following mechanisms:
mutations of Bcr-Abl
overexpression of Bcr-Abl
other proteins involved in cancer pathways, such as the Src pathway
Mutations can change the shape of the Bcr-Abl protein. When this happens, Imatinib, the current standard treatment, may be unable to block its activity. Sprycel is an oral, multi-targeted therapy that can inhibit the action of Bcr-Abl in the presence of all but one known mutation.
The European Medicines Agency reviewed the efficacy and safety of Sprycel based on the analysis of five phase 2 multi-centre studies in patients with resistance or intolerance to Imatinib in all phases of chronic myeloid leukaemia or Ph+ acute lymphoblastic leukaemia.
In the 911 patients receiving Sprycel in clinical trials, the most common side effects were fluid retention ( including pleural effusion and peripheral oedema ), gastrointestinal ( diarrhoea, nausea and vomiting ), skin rash, headache, haemorrhage, fatigue, and dyspnoea.
Myelosuppression was reported in all studies and was generally reversible. The frequency was higher in patients with advanced chronic myeloid leukaemia or Ph+ acute lymphoblastic leukaemia than in chronic phase chronic myeloid leukaemia.
Source: EMEA, 2006