P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808
P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808
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DOI：
10.1182/blood-2009-07-229492
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发表时间：
2010-09-02
期刊：
影响因子：
20.3
通讯作者：
Larson, Richard A.
中科院分区：
文献类型：
--
作者：
Kolitz, Jonathan E.;George, Stephen L.;Larson, Richard A.
癌症和白血病组B 19808（CALGB 19808）是第二代P-糖蛋白（Pgp）调节剂在年龄小于60岁的未经治疗的急性髓性白血病（AML）患者中的唯一随机试验。我们将302例患者随机分配接受诱导化疗方案，包括阿糖胞苷（Ara-C; A），柔红霉素（D）和依托泊苷（E），不加（ADE）或加（ADEP）PSC-833（P）。两种方案的完全缓解率均为75%。可逆的3级和4级肝和粘膜毒性在ADEP中明显更常见。治疗相关死亡率为7%，诱导组之间无差异。在ADE中，高剂量D未观察到过度心脏毒性。ADE组和ADEP组的中位无病生存期分别为1.34年和1.09年（P = 0.74，对数秩检验）; ADE组和ADEP组的中位总生存期分别为1.86年和1.69年（P = 0.82）。在任何可识别的患者亚组中均无治疗差异的证据。PSC-833对Pgp介导的药物外排的抑制并未改善年轻AML患者的临床结局。该试验在www.clinicaltrials.gov上注册为#NCT00006363。（血。2010;116（9）：1413-1421）
Cancer and Leukemia Group B 19808 (CALGB 19808) is the only randomized trial of a second-generation P-glycoprotein (Pgp) modulator in untreated patients with acute myeloid leukemia (AML) younger than age 60 years. We randomly assigned 302 patients to receive induction chemotherapy regimens consisting of cytosine arabinoside (Ara-C; A), daunorubicin (D), and etoposide (E), without (ADE) or with (ADEP) PSC-833 (P). The incidence of complete remission was 75% with both regimens. Reversible grade 3 and 4 liver and mucosal toxicities were significantly more common with ADEP. Therapy-related mortality was 7% and did not differ by induction arm. Excess cardiotoxicity was not seen with high doses of D in ADE. The median disease-free survival was 1.34 years in the ADE arm and 1.09 years in the ADEP arm (P = .74, log-rank test); the median overall survival was 1.86 years in the ADE arm and 1.69 years in the ADEP arm (P = .82). There was no evidence of a treatment difference within any identifiable patient subgroup. Inhibition of Pgp-mediated drug efflux by PSC-833 did not improve clinical outcomes in younger patients with untreated AML. This trial was registered at www.clinicaltrials.gov as #NCT00006363. (Blood. 2010;116(9):1413-1421)