Results of triple therapy with interferon-alpha, cytarabine, and homoharringtonine, and the impact of adding imatinib to the treatment sequence in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase
Results of triple therapy with interferon-alpha, cytarabine, and homoharringtonine, and the impact of adding imatinib to the treatment sequence in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase
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DOI：
10.1002/cncr.11620
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发表时间：
2003-09-01
期刊：
影响因子：
6.2
通讯作者：
Kantarjian, HM
中科院分区：
文献类型：
--
作者：
O'Brien, S;Giles, F;Kantarjian, HM
背景在发现甲磺酸伊马替尼（一种Bcr-Abl选择性酪氨酸激酶抑制剂）之前，三种药物（干扰素-α（IFN-α）、阿糖胞苷（ara-C）和高三尖杉酯碱（HHT））已被证明具有抗费城染色体（Ph）阳性慢性髓细胞性白血病（CML）的活性。本研究的目的是评价IFN-α、阿糖胞苷和HHT三联疗法治疗新诊断的Ph阳性CML的疗效，并评估伊马替尼序贯治疗对总体缓解的影响。90例Ph阳性慢性早发型CML患者接受三联方案治疗。治疗包括500万单位（MU）/m2的IFN-α皮下（s.c.阿糖胞苷10 mg s.c. HHT 2.5 mg/m2，持续输注，每日24小时，每月5次。经过16.5个月的中位治疗后，78例患者的治疗改为每天口服400 mg伊马替尼。在三联治疗方案中，85例患者（94%）达到完全血液学缓解，67例患者（74%）达到细胞遗传学缓解（Ph抑制至小于或等于90%），其中20例患者（22%）为完全缓解（Ph 0%），42例患者（46%）为主要缓解。骨髓抑制显著，导致给药方案大幅减少。治疗12个月后，IFN-α的中位剂量为1.6 MU/m2/d，阿糖胞苷的中位剂量为1.85 mg/d，HHT的中位天数为每月2天。只有3例患者在接受三联方案时发生了急变期。随着伊马替尼治疗的改变，目前57例患者（63%）处于完全细胞遗传学缓解，69例患者（76%）处于主要细胞遗传学缓解。整个研究组的中位随访时间为46个月，估计5年生存率为88%，迄今为止只有8例患者（9%）发展为急变期。IFN-α，ara-C和HHT的顺序，然后是伊马替尼（由后一种药物的发现强加），估计5年生存率为88%。这一发现表明，伊马替尼联合方案可能会改善CML的预后。(C)2003年美国癌症协会。
BACKGROUND. Before the discovery of imatinib mesylate, a Bcr-Abl selective tyrosine kinase inhibitor, three agents, interferon-alpha (IFN-alpha), cytarabine (ara-C), and homoharringtonine (HHT), had demonstrated activity against Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) as single agents and in couplet combinations. The goals of the current study were to evaluate the efficacy of the triple combination regimen with IFN-alpha, ara-C, and HHT in newly diagnosed Ph-positive CML and to assess the impact of the added sequential therapy with imatinib on overall prognosis.METHODS. Ninety patients with Ph-positive CML in early chronic phase received the triple regimen. Therapy consisted of 5 million units (MU)/m(2) IFN-alpha subcutaneously (s.c. daily, ara-C 10 mg s.c. daily, and HHT 2.5 mg/m(2) by continuous infusion over 24 hours daily x 5 every month. After a median duration of 16.5 months of therapy, 78 patients had their therapy changed to 400 mg orally administered imatinib daily.RESULTS. with the triple regimen, 85 patients (94%) achieved complete hematologic response and 67 patients (74%) had a cytogenetic response (Ph suppression to less than or equal to 90%) which was complete (Ph 0%) in 20 patients (22%) and major in 42 patients (46%). Myelosuppression was significant, resulting in considerable reductions in the dose schedules. After 12 months of therapy, the median IFN-alpha dose was 1.6 MU/m(2) daily, the median ara-C dose was 1.85 mg daily, and the median number of HHT days was 2 every month. Only three patients developed blastic phase while receiving the triple regimen. With the change to imatinib therapy, currently 57 patients (63%) are in complete cytogenetic response and 69 patients (76%) in major cytogenetic response. With a median follow-up time of 46 months for the total study group, the estimated 5-year survival rate was 88%, and only 8 patients (9%) to date have developed blastic phase.CONCLUSIONS. The sequence of IFN-alpha, ara-C, and HHT followed by imatinib (imposed by the discovery of the latter drug) resulted in an estimated 5-year survival rate of 88%. This finding suggests that imatinib combination regimens may improve the prognosis in CML. (C) 2003 American Cancer Society.