Benjamin R S, Keating M J, Swenerton K D, Legha S, McCredie K B
Cancer Treat Rep. 1979 May;63(5):925-9.
One hundred and thirty-three patients, 94 with acute luekemia and 39 with solid tumors, received rubidazone, alone or in combination, at M. D. Anderson Hospital. The initial study, a phase I--II study carried out in 39 patients with acute leukemia, revealed substantial antileukemic activity with optimal results at a dose level of 450 mg/m2. Toxic manifestations included an acute reaction suggestive of histamine release with dose-limiting mucositis at a dose of 600 mg/m2. Forty-seven patients with acute leukemia were treated at phase II dose levels. Thirteen of 32 patients (42%) with acute myelogenous leukemia and seven of ten patients (70%) with acute lymphocytic leukemia achieved complete remission. Twenty-seven previously untreated patients with acute leukemia who were greater than 50 years old were treated with rubidazone in combination with cytosine arabinoside, vincristine, and prednisone. Fifteen patients (50%) achieved complete remission including 12 of 15 patients (73%) who were treated at a dose of 200 mg/m2 of rubidazone on Day 1 and a dose of 70 mg/m2/day X 7 days of cytosine arabinoside (continuous infusion). For patients with solid tumors, the dose-limiting toxic effect was myelosuppression at a dose of 200 mg/m2. Other toxicity at that dose level was minimal. The best responses were seen in patients with carcinoma of the period with two of four evaluable patients showing objective tumor regression. Of six previously untreated patients with thyroid carcinoma none responded, and in a phase II study of patients with breast cancer there were no partial remissions among 13 patients. Cardiac toxicity, manifested by congestive heart failure, occurred in seven patients at cumulative doses of 1050--2600 mg/m2 of rubidazone; all patients had had prior anthracycline therapy at low doses. Rubidazone has been shown to be an active antileukemic agent, but appears to be less active than Adriamycin in our studies of patients with solid tumors.
133名患者，其中94名患有急性白血病，39名患有实体瘤，在MD安德森医院接受了单独或联合使用鲁比达唑的治疗。最初的研究是一项在39名急性白血病患者中进行的I-II期研究，结果显示在剂量水平为450mg/m²时具有显著的抗白血病活性且效果最佳。毒性表现包括提示组胺释放的急性反应，在剂量为600mg/m²时出现剂量限制性粘膜炎。47名急性白血病患者接受了II期剂量水平的治疗。32名急性髓性白血病患者中有13名（42%）以及10名急性淋巴细胞白血病患者中有7名（70%）实现了完全缓解。27名年龄大于50岁的既往未治疗的急性白血病患者接受了鲁比达唑联合阿糖胞苷、长春新碱和泼尼松的治疗。15名患者（50%）实现了完全缓解，其中包括15名患者中的12名（73%），这些患者在第1天接受了200mg/m²的鲁比达唑治疗以及70mg/m²/天×7天的阿糖胞苷（持续输注）治疗。对于实体瘤患者，剂量限制性毒性作用是在剂量为200mg/m²时出现骨髓抑制。该剂量水平下的其他毒性极小。在可评估的4名患者中有2名出现客观肿瘤消退，这在患有该时期癌症的患者中反应最佳。6名既往未治疗的甲状腺癌患者均无反应，并且在一项针对乳腺癌患者的II期研究中，13名患者中无部分缓解情况。7名患者在累积剂量为1050 - 2600mg/m²的鲁比达唑时出现了以充血性心力衰竭为表现的心脏毒性；所有患者之前均接受过低剂量的蒽环类药物治疗。鲁比达唑已被证明是一种有效的抗白血病药物，但在我们对实体瘤患者的研究中，其活性似乎低于阿霉素。
