Kraut E H, Walker M J, Staubus A, Gochnour D, Balcerzak S P
Division of Hematology and Oncology, Ohio State University, Columbus 43210, USA.
Cancer Invest. 1997;15(4):318-20. doi: 10.3109/07357909709039732.
Topotecan (S-9-dimethyl-10-hydroxycamptothecin hydrochloride SKF 104864-A) is a semisynthetic analog of the alkaloid camptothecin and, similar to the parent compound, a potent inhibitor of topoisomerase I. The cytotoxicity induced by topotecan appears due to interference with the normal breakage reunion reaction of topoisomerase I leading to DNA damage and cell death. Since preclinical studies of topotecan suggested antitumor activity against refractory solid tumors, a phase II trial of the drug was initiated in melanoma patients with recurrent and/or metastatic disease. Topotecan 1.5 mg/m2 was given as a daily 30-min infusion for 5 days and repeated every 21-28 days. Seventeen patients were entered into the treatment program with all evaluable for toxicity but I patient, inevaluable for response. There were no objective responses. Toxicity was predominantly severe myelosuppression, which occurred in 12 of 17 (70%) patients. Topotecan in this dose and schedule is inactive in malignant melanoma.
拓扑替康（S-9-二甲基-10-羟基喜树碱盐酸盐，SKF 104864-A）是生物碱喜树碱的半合成类似物，与母体化合物相似，是一种强效的拓扑异构酶I抑制剂。拓扑替康诱导的细胞毒性似乎是由于干扰了拓扑异构酶I的正常断裂重连反应，导致DNA损伤和细胞死亡。由于拓扑替康的临床前研究表明其对难治性实体瘤具有抗肿瘤活性，因此在患有复发性和/或转移性疾病的黑色素瘤患者中启动了该药物的II期试验。拓扑替康以1.5mg/m²的剂量每天输注30分钟，共5天，并每21 - 28天重复一次。17名患者进入治疗方案，所有患者均可评估毒性，但有1名患者无法评估反应。没有观察到客观缓解。毒性主要是严重的骨髓抑制，17名患者中有12名（70%）出现这种情况。该剂量和给药方案的拓扑替康对恶性黑色素瘤无效。
