Chang P, Wiernik P H
Clin Pharmacol Ther. 1976 Nov;20(5):605-10. doi: 10.1002/cpt1976205605.
In a prospectively randomized study, 17 evaluable patients treated with adriamycin alone, 60 mg/m2 intravenously every 3 wk, were compared with 14 patients treated with adriamycin in the same dose and schedule plus streptozotocin. 500 mg/m2/day intravenously for 5 days every 3 wk. All patients had advanced sarcomas, but none had previously received either adriamycin or streptozotocin. Objective responses were seen in 9 patients on the single drug arm (4 with more than 50% tumor shrinkage and 5 with stabilization of disease), and in 8 patients given the combination drug arm (2 with more than 50% tumor shrinkage and 6 with stabilization of disease). Duration of response and survival from treatment for both treatment groups were similar. Transient hepatic dysfunction, renal function abnormalities, and nausea with vomiting were additive in the combination drug arm, the last two limiting therapy most. Leukopenia, thrombocytopenia, and mucositis appeared to be synergistically increased in patients receiving both adriamycin and streptozotocin. Patients with abnormal pretreatment renal function were able to tolerate the combination therapy without undue incidence of severity of renal toxicity. Patients who developed transient streptozotocin-related renal dysfunction were able to tolerate further doses of streptozotocin after their renal parameters normalized. Adriamycin in combination with streptozotocin did not offer any therapeutic advantage over adriamycin alone.
在一项前瞻性随机研究中,将17例仅接受阿霉素治疗的可评估患者(每3周静脉注射60mg/m²)与14例接受相同剂量和疗程阿霉素加链脲佐菌素治疗的患者进行比较。链脲佐菌素为每3周静脉注射500mg/m²/天,共5天。所有患者均患有晚期肉瘤,但此前均未接受过阿霉素或链脲佐菌素治疗。单药治疗组有9例患者出现客观缓解(4例肿瘤缩小超过50%,5例病情稳定),联合用药组有8例患者出现客观缓解(2例肿瘤缩小超过50%,6例病情稳定)。两个治疗组的缓解持续时间和治疗后的生存期相似。联合用药组中,短暂性肝功能障碍、肾功能异常以及恶心伴呕吐的症状有所叠加,后两者对治疗的限制最大。接受阿霉素和链脲佐菌素治疗的患者中,白细胞减少、血小板减少和粘膜炎似乎呈协同增加。治疗前肾功能异常的患者能够耐受联合治疗,且肾毒性的发生率和严重程度均未出现异常增加。出现短暂性链脲佐菌素相关肾功能障碍的患者在肾功能参数恢复正常后能够耐受进一步剂量的链脲佐菌素。阿霉素联合链脲佐菌素相较于单独使用阿霉素并未显示出任何治疗优势。