Treatment
Historical Perspective
Chemotherapy: Hydroxyurea and Busulfan
Before the introduction of Glivec® (imatinib), the oral chemotherapeutic agents hydroxyurea (an inhibitor of deoxyribonucleic acid [DNA] synthesis) and busulfan (an alkylating agent) were the drugs of choice for patients who were not stem-cell transplantation (SCT) candidates or who were intolerant of or refractory to interferon alfa (IFN-α). Hydroxyurea and busulfan were also used before SCT. Although haematological responses (HRs) have been reported in up to 90% of patients with newly diagnosed chronic myeloid leukaemia (CML) who were treated with these agents, they rarely induce a cytogenetic response and disease progression is not affected.1,2
Hydroxyurea is generally better tolerated than busulfan and is more effective: 5-year survival rates are 44% versus 32%, respectively, with a significantly longer median survival of 58 months versus 45 months.3 Because neither drug inhibits the progression of CML, these agents are considered palliative therapy for symptoms caused by leukocytosis.1,2
References:
1. Sawyers CL. Chronic myeloid leukemia. N Engl J Med. 1999;340:1330-1340.
2. Faderl S, Talpaz M, Estrov Z, Kantarjian HM. Chronic myelogenous leukemia: biology and therapy. Ann Intern Med. 1999;131:207-219.
3. Hehlmann R, Heimpel H, Hasford J, et al. Randomized comparison of busulfan and hydroxyurea in chronic myelogenous leukemia: prolongation of survival by hydroxyurea. The German CML Study Group. Blood. 1993;82:398-407.