INTERFERON-ALPHA-2C AND LD ARA-C FOR THE TREATMENT OF PATIENTS WITH CML - RESULTS OF THE AUSTRALIAN MULTICENTER PHASE-II STUDY

Small pilot studies of patients with CML have reported on encouraging response rates after treatment with interferon-alpha (IFN alpha) in co mbination with low-dose cytosine arabinoside (LD ara-C). We therefore initiated a multi-center phase II trial in order to investigate the ef ficacy and tolerability of this combination in newly diagnosed patient s with Ph-positive chronic myelogenous leukemia (CML). Eighty-four pat ients were treated with IFN-alpha-2c at daily subcutaneous doses of 3. 5 MU and LD ara-C added subcutaneously for 10 days every month at a do se of 10 mg/m(2), following an initial reduction of WBC to less than 2 0 x 10(9)/l with hydroxyurea (HU). Within a median observation period of 28 (5-59) months the patients received a median of 7 (1-35) IFN alp ha and LD ara-C cycles. Treatment was stopped due to side effects in 1 6 cases (19%) and to primary or secondary treatment failure in 38 case s (45%). In 45 patients (54%) complete hematological response (CHR) wa s achieved; in 39 patients (46%) cytogenetic responses including 15 (1 8%) complete cytogenetic responses (CHR) were observed. Median duratio n of cytogenetic responses was 15 months. Relapses were seen in 8/15 p atients (53%) with complete cytogenetic remission (CCR), in 3/6 patien ts (50%) with partial cytogenetic response and in 9/18 patients (50%) with minor cytogenetic response. In conclusion, the combination of IFN alpha and LD ara-C resulted in encouraging rates of hematological and cytogenetic responses in patients with CML with low to moderate toxic ity. (C) 1997 Elsevier Science Ltd.