Garcia-Manero Guillermo, Talpaz Moshe, Giles Francis J, Cortes Jorge, Faderl Stefan, O'Brien Susan, Thomas Deborah, Verstovsek Srdan, Beth Rios Mary, Shan Jianquin, Ferrajoli Alessandra, Wierda William, Kantarjian Hagop M
Department of Leukemia, The University of Texas MD Anderson Cancer, Houston, Texas 77030, USA.
Cancer. 2003 Jun 15;97(12):3010-6. doi: 10.1002/cncr.11424.
To evaluate the activity and toxicity of weekly Schering 54301, a polyethylene glycol formulation of interferon- alpha-2b (PEG-IFN-alpha-2b), with cytosine arabinoside (ara-C) in patients with chronic myelogenous leukemia (CML).
Seventy-six patients with Philadelphia chromosome (Ph)-positive early chronic-phase CML were treated with the combination of PEG-IFN-alpha-2b and ara-C (10 mg daily subcutaneously [s.c.]). The starting dose of PEG-IFN-alpha-2b was 6 microg/kg s.c. weekly in the first 24 patients but was reduced to 4.5 microg/kg in the next 52 patients.
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-alpha-2b and ara-C doses delivered were 3 microg/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-alpha and cytarabine.
The combination of PEG-IFN-alpha-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-alpha-2b in future combination studies is 3 microg/kg or less.
评估聚乙二醇化干扰素-α-2b（PEG-IFN-α-2b）即先灵葆雅54301（每周给药一次）联合阿糖胞苷（ara-C）治疗慢性粒细胞白血病（CML）患者的活性及毒性。
76例费城染色体（Ph）阳性的慢性期CML患者接受PEG-IFN-α-2b联合ara-C（每日10mg皮下注射）治疗。前24例患者PEG-IFN-α-2b的起始剂量为每周6μg/kg皮下注射，后52例患者起始剂量减至4.5μg/kg。
总体而言，73%的患者获得完全血液学缓解，35%的患者获得主要细胞遗传学缓解（Ph<35%），21%的患者获得完全细胞遗传学缓解（Ph=0%）。中位随访19个月，预计2年生存率为89%。24%的患者因III-IV级毒性而停药。需要降低剂量的常见严重副作用包括中性粒细胞减少（49%）、疲劳（43%）和神经毒性（17%）。治疗12个月时，PEG-IFN-α-2b和ara-C的中位给药剂量分别为每周3μg/kg和每日7.5mg。该联合用药的活性和毒性特征与既往接受干扰素-α和阿糖胞苷治疗的患者相似。
PEG-IFN-α-2b联合ara-C在慢性期CML患者中具有活性，但在所使用的剂量方案下具有显著毒性。在未来的联合研究中，PEG-IFN-α-2b的推荐剂量为3μg/kg或更低。
