Möbus V, Pfaff P N, Volm T, Kreienberg R, Kaubitzsch S
Department of Obstetrics and Gynecology, Städtische Kliniken, Frankfurt, Germany.
Anticancer Res. 2001 Sep-Oct;21(5):3551-6.
In several phase II and III topotecan studies the large number of patients with stable disease is striking. Since no severe organ toxicity has been described for topotecan, long-term therapy with topotecan seems to be reasonable. In this summary we present evidence, that long-term topotecan therapy can be managed without cumulative hematological and non-hematological toxicity.
Thirty-three patients with recurrent ovarian cancer, who were treated with at least 7 courses of topotecan, were evaluated in this retrospective study (patient database from SmithKline Beecham, Germany). Most of the patients had more than 2 previous courses of chemotherapy. The starting dose was between 1.0 and 1.5 mg/m2 topotecan administered for 5 days every 3 weeks as an i.v. infusion. All patients were evaluated for toxicity, 32 patients for response.
The 33 patients received 343 courses of topotecan, an average of more than 10 courses per patient. The highest number of courses given to a single patient was 33. The hematotoxicity was in the expected range, but toxicity was not cumulative. The number of interventions for growth factors and blood cell transfusions were constant over the whole therapy. Dose reductions were conducted in more than 75% of the patients as early as in course two. There was no grade 3 or 4 non-hematological toxicity. Alopecia was the only toxicity to be cumulative. Remissions were observed in 12 out of 32 eligible patients. The remissions were achieved after an average of 4.3 courses (range 2-7). The median time to progression was 33 weeks.
Long-term therapy with topotecan is reasonable and can be conducted without cumulative hematological toxicity.
在多项拓扑替康的II期和III期研究中，病情稳定的患者数量众多，令人瞩目。由于尚未有拓扑替康严重器官毒性的报道，因此拓扑替康的长期治疗似乎是合理的。在本综述中，我们提供证据表明，拓扑替康的长期治疗可以在不产生累积血液学和非血液学毒性的情况下进行。
本回顾性研究（来自德国史克必成公司的患者数据库）评估了33例复发性卵巢癌患者，这些患者接受了至少7个疗程的拓扑替康治疗。大多数患者之前接受过超过2个疗程的化疗。起始剂量为每平方米体表面积1.0至1.5毫克拓扑替康，每3周静脉输注5天。所有患者均评估了毒性反应，32例患者评估了疗效。
33例患者共接受了343个疗程的拓扑替康治疗，平均每位患者超过10个疗程。单个患者接受的最高疗程数为33个。血液毒性在预期范围内，但毒性并未累积。在整个治疗过程中，生长因子干预和血细胞输注的次数保持恒定。超过75%的患者在第2个疗程时就开始减量。没有3级或4级非血液学毒性。脱发是唯一具有累积性的毒性反应。32例符合条件的患者中有12例出现缓解。缓解平均在4.3个疗程后出现（范围为2至7个疗程）。中位进展时间为33周。
拓扑替康的长期治疗是合理的，且可以在不产生累积血液学毒性的情况下进行。
