Treatment of Philadelphia chromosome-positive chronic myelogenous leukemia with weekly polyethylene glycol formulation of interferon-alpha-2b and low-dose cytosine arabinoside

BACKGROUND. To evaluate the activity and toxicity of weekly Schering 54301, a polyethylene glycol formulation of interferon-α-2b (PEG-IFN-α-2b), with cytosine arabinoside (ara-C) in patients with chronic myelogenous leukemia (CML). METHODS. Seventy-six patients with Philadelphia chromosome (Ph)-positive early chronic-phase CML were treated with the combination of PEG-IFN-α-2b and ara-C (10 mg daily subcutaneously [s.c.]). The starting dose of PEG-IFN-α-2b was 6 μg/kg s.c. weekly in the first 24 patients but was reduced to 4.5 μg/kg in the next 52 patients. RESULTS. Overall, 73% of patients had a complete hematologic response, 35% of patients had a major cytogenetic response (Ph < 35%), and 21% of patients had a complete cytogenetic response (Ph = 0%). With a median follow-up of 19 months, the estimated 2-year survival rate was 89%. Therapy was discontinued in 24% of patients due to Grade III-IV toxicity. Frequent severe side effects that required dose reductions included neutropenia (49%), fatigue (43%), and neurologic toxicity (17%). The median PEG-IFN-α-2b and ara-C doses delivered were 3 μg/kg weekly and 7.5 mg daily, respectively, at 12 months of therapy. The activity and toxicity profiles of this combination was similar to those observed in historical patients treated with IFN-α and cytarabine. CONCLUSIONS. The combination of PEG-IFN-α-2b and ara-C is active but has significant toxicity in patients with chronic-phase CML at the dose schedule used. The recommended dose of PEG-IFN-α-2b in future combination studies is 3 μg/kg or less.