Kuratsu J I, Arita N, Kayama T, Kubo N, Mori T, Sawamura Y, Ushio Y
Department of Neurosurgery, Faculty of Medicine, Kagoshima University, Japan.
J Neurooncol. 2000 Jun;48(2):145-9. doi: 10.1023/a:1006482006138.
KRN8602 (MX2) is a newly developed morpholino anthracycline that crosses the blood-brain barrier where it becomes distributed in brain tissue after intravenous administration. This morpholino anthracycline has been found to be effective against human glioma cells and the intracerebrally transplanted tumors in vivo, We performed a phase II trial using KRN8602 as a single agent in malignant glioma patients who had not received prior adjuvant therapy. The 13 patients (5 glioblastomas, 7 anaplastic astrocytomas and 1 malignant oligodendroglioma) enrolled received at least 1 cycle of KRN8602 at 35 mg/m2/day in 3-4 week intervals by intravenous bolus. Ten of these patients could be evaluated for response, and 13 for toxicity. Three patients (1 glioblastoma and 2 anaplastic astrocytomas) demonstrated a complete response (3/10, 30%). Concerning side effects, myelosuppression was moderately severe, with 30.7% of patients developing grade 3 leukopenia. Severe nausea/vomiting was observed in 69% of the patients, however, cardiotoxicity was not observed. The results indicate that KRN8602 demonstrated modest activity against malignant glioma with relatively severe, but manageable toxicity. Further assessment of the efficacy and toxicity of KRN8602 against malignant glioma may be worthwhile.
KRN8602（MX2）是一种新开发的吗啉代蒽环类药物，它能够穿过血脑屏障，静脉给药后可在脑组织中分布。已发现这种吗啉代蒽环类药物对人胶质瘤细胞和体内脑内移植肿瘤有效。我们对未接受过先前辅助治疗的恶性胶质瘤患者进行了一项以KRN8602作为单一药物的II期试验。入组的13例患者（5例胶质母细胞瘤、7例间变性星形细胞瘤和1例恶性少突胶质细胞瘤）以35mg/m²/天的剂量，每3 - 4周通过静脉推注接受至少1个周期的KRN8602治疗。其中10例患者可评估疗效，13例评估毒性。3例患者（1例胶质母细胞瘤和2例间变性星形细胞瘤）表现出完全缓解（3/10，30%）。关于副作用，骨髓抑制为中度严重，30.7%的患者出现3级白细胞减少。69%的患者观察到严重恶心/呕吐，然而未观察到心脏毒性。结果表明，KRN8602对恶性胶质瘤显示出一定活性，毒性相对严重但可控制。进一步评估KRN8602对恶性胶质瘤的疗效和毒性可能是值得的。
