While its efficacy has been outstanding, Glivec has also been well tolerated in patients with CML. Most patients experience undesirable adverse events that are generally of mild to moderate severity, including gastrointestinal side effects that may be minimised when the medication is taken with a meal and a large glass of water. The most frequently reported drug-related adverse events were mild nausea, vomiting, diarrhoea, abdominal pain, fatigue, myalgia, muscle cramps, and rash-which were easily manageable; superficial oedemas were also a common finding.1 Fewer than 5% of patients have experienced serious adverse effects (such as skin rashes, liver toxicity, fluid retention syndrome, and haemorrhages) that led to discontinuation of treatment. Cardiac disorders including cardiac tamponade and skin disorders including acute febrile neutrophilic dermatosis (Sweet's syndrome) have rarely been reported (≤ 1/1000).1 Data from a larger patient cohort followed for 8 years have demonstrated that congestive heart failure is a rare event with Glivec therapy, primarily observed in elderly patients with preexisting cardiac conditions (1.8%, 22/1276 patients). The study authors recommend close monitoring of patients with a history of cardiac conditions.2 Analysis of patients with CML who developed phosphataemia during treatment with Glivec indicate that it may be related to digestive side effects, the symptoms of which may be alleviated by management of diarrhoea.3
Long-term follow-up in the IRIS trial confirmed that Glivec is well tolerated; moreover, the frequency of adverse events decreased substantially over time with continued Glivec therapy.4
Glivec represents a significant medical advance in the treatment of neoplastic disease. As the first and most established molecularly targeted, rationally designed drug therapy for CML, Glivec establishes a new paradigm for future drug development. The clinical trial data have provided proof of its clinical and survival benefits, and with its specific mechanism of action, Glivec offers an effective and well-tolerated therapeutic option for patients with Ph+ CML.
1. Glivec Summary of Product Characteristics [SMPC]. Basel, Switzerland: Novartis Pharma AG; 2006.
2. Atallah E, Durand JB, Kantarjian H, et al. Congestive heart failure is a rare event in patients (pts) receiving imatinib therapy [abstract]. Blood. 2006;108:609a. Abstract 2146.
3. Legros L, Breuil V, Farrari P, Tests J, Cassuto J-L. Hypophosphatemia observed in chronic myeloid leukemia patients treated with imatinib mesylate (Gleevec®) is related to digestive side-effects [abstract]. Blood. 2006;108:274b. Abstract 4765.
4. Kantarjian HM, Larson RA, Guilhot F, G. OBS, Druker BJ, group obotIs. on behalf of the IRIS study group. Declining rates of adverse events (AEs), rare occurrence of serious AEs (SAEs), and no unexpected long-term side effects at 5 years in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP) initially treated with imatinib (IM) in the International Randomized Study of Interferon vs STI571 (IRIS) [abstract]. Blood. 2006;108:605a. Abstract 2136.