Abstract
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. Cancer 2003;97:3010–6. © 2003 American Cancer Society.
DOI 10.1002/cncr.11424