Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Cancer Sci. 2011 Jul;102(7):1358-65. doi: 10.1111/j.1349-7006.2011.01957.x. Epub 2011 May 18.
In order to investigate better molecular-target therapy for acute myeloid leukemia (AML), we conducted a phase I trial of a combination of gemtuzumab ozogamicin (GO) with conventional chemotherapy. Between January 2007 and December 2009, a total of 19 adult Japanese patients with relapsed or refractory CD33-positive AML (excluding acute promyelocytic leukemia) were enrolled. All registered patients received a standard dose of cytarabine (Ara-C) (100 mg/m(2) × 7 days), combined with either idarubicin (IDR) (10-12 mg/m(2) × 3 days) or daunorubicin (DNR) (50 mg/m(2) × 3-5 days), and then GO (3-5 mg/m(2) ), which was administered 1 day after the last infusion of IDR (IAG regimen) or DNR (DAG regimen). While doses of both GO and IDR and the administration period of only DNR were increased, the dose-limiting toxicity (DLT) was assessed. Among 19 patients (nine in the IAG regimen, 10 in the DAG regimen), the median age was 59 years (range 33-64), and the relapsed/refractory ratio was 13/6. In the therapy using 3 mg/m(2) GO in the IAG or DAG regimen, grade 3/4 leukopenia and neutropenia were observed in all patients, but none had grade 3/4 non-hematological toxicities, except febrile neutropenia. Three patients in the IAG regimen who were administered 5 mg/m(2) GO showed DLT. No patients had veno-occlusive disease or sinusoidal obstructive syndrome. In conclusion, 3 mg/m(2) GO combined with Ara-C and IDR or DNR can be safely administered, and phase II trials should be conducted to investigate the clinical efficacy of the combination therapy.
为了探索急性髓系白血病（AML）更好的分子靶向治疗方法，我们进行了吉妥珠单抗奥佐米星（GO）联合常规化疗的 I 期临床试验。2007 年 1 月至 2009 年 12 月，共纳入 19 例复发或难治性 CD33 阳性 AML（不包括急性早幼粒细胞白血病）的成年日本患者。所有登记患者均接受标准剂量阿糖胞苷（Ara-C）（100 mg/m2×7 天），联合伊达比星（IDR）（10-12 mg/m2×3 天）或柔红霉素（DNR）（50 mg/m2×3-5 天），然后给予 GO（3-5 mg/m2），在最后一次 IDR（IAG 方案）或 DNR（DAG 方案）输注后第 1 天给予。在增加 GO 和 IDR 的剂量以及 DNR 的给药时间的同时，评估剂量限制性毒性（DLT）。在 19 例患者中（IAG 方案 9 例，DAG 方案 10 例），中位年龄为 59 岁（范围 33-64 岁），复发/难治性比例为 13/6。在 IAG 或 DAG 方案中使用 3 mg/m2GO 的治疗中，所有患者均出现 3/4 级白细胞减少和中性粒细胞减少，但除发热性中性粒细胞减少外，无 3/4 级非血液学毒性。IAG 方案中接受 5 mg/m2GO 治疗的 3 例患者出现 DLT。无患者发生静脉闭塞病或窦阻塞综合征。总之，3 mg/m2GO 联合 Ara-C 和 IDR 或 DNR 可安全给药，应进行 II 期临床试验以研究联合治疗的临床疗效。
