Imatinib: new indication. New indications, but not robust evidence.

(1) Imatinib, a tyrosine kinase inhibitor, was first marketed for the treatment of chronic myeloid leukaemia and some gastrointestinal stromal tumours. Its indications have gradually expanded over the years. (2) There is no consensus treatment for adults with Philadelphia chromosome-positive acute lymphoblastic leukaemia. In a trial comparing imatinib versus chemotherapy as initial treatment for 55 patients, the haematological response rate was higher with imatinib. Non-comparative trials provided haematological response rates of about 90%, but it is not known whether or not this translates into a survival advantage. In three non-comparative trials including patients with relapsed or refractory disease after chemotherapy, 50% of patients showed a survival time of at least 7 months. In the absence of any direct comparisons, we do not know if this represents an improvement over the results obtained with the best palliative care. (3) The only potential cure for myelodysplastic syndromes is allogeneic haematopoietic stem cell transplantation but this is not always feasible. Some myelodysplastic syndromes are associated with myeloproliferation and PDGFR gene rearrangements; imatinib is the first drug available for these patients. The manufacturer has compiled data on 55 patients treated with imatinib. Most patients had a favourable haematological response, but no survival data were published. (4) The severity of the hypereosinophilic syndrome is highly variable. Forms associated with FIP1L1-PDGFRalpha gene rearrangements have a poor prognosis. Clinical evaluation of imatinib in this setting is based on a compilation of data concerning 176 treated patients. The haematological response rate was high in patients with the mutant gene, but it is not known whether this translated into increased survival. (5) Dermatofibrosarcoma protuberans is a rare form of mainly localised skin cancer. Treatment is based on surgical excision but relapses are frequent. In one series, 9 out of 12 patients treated with imatinib had at least a partial tumour response, making surgical excision possible in 3 cases. (6) Imatinib has diverse and frequent adverse effects; nausea and vomiting, oedema, fluid retention, cutaneous disorders and heart failure. There is some evidence pointing to a risk of urologic cancers and altered bone metabolism.