Garaventa Alberto, Luksch Roberto, Biasotti Simona, Severi Gianluca, Pizzitola Maria Rosa, Viscardi Elisabetta, Prete Arcangelo, Mastrangelo Stefano, Podda Marta, Haupt Riccardo, De Bernardi Bruno
Department of Pediatric Hematology/Oncology, Giannina Gaslini Children's Hospital, Genoa, Italy.
Cancer. 2003 Dec 1;98(11):2488-94. doi: 10.1002/cncr.11797.
A Phase II trial in children with advanced neuroblastoma was carried out in five Italian institutions to evaluate the antitumor activity and tolerability of topotecan followed by vincristine and doxorubicin.
Children older than age 1 year with Stage III or Stage IV neuroblastoma, all of whom had been treated previously with chemotherapy and were diagnosed with either refractory or recurrent disease, were treated with topotecan at an intravenous dose of 1.5 mg/m(2) (the dose was 0.75 mg/m(2) for patients who were treated within 1 year of previous megatherapy) per day for 5 days followed by 48-hour intravenous infusions of 2 mg/m(2) vincristine and 45 mg/m(2) doxorubicin. Cycles of therapy were repeated every 3 weeks.
Twenty-five patients (2 with Stage III disease and 23 with Stage IV disease; 19 with refractory disease and 6 with recurrent disease) were treated with a total of 115 cycles. Four patients had complete responses, 12 patients had partial responses, 4 patients had minor responses or stable disease, and 5 patients had tumor progression. The overall response rate (including complete and partial responses) was 64% (95% confidence interval, 43-82%). Fifteen patients were alive at the time of the current report and were progression free at 4-16 months (median, 9 months) after the first course of this treatment. Toxicity generally was limited to the hematopoietic system. Dose-limiting toxicity was observed in only 1 patient (Grade 4 liver toxicity). There were no deaths due to infectious or toxic causes.
The topotecan-vincristine-doxorubicin combination was active and well tolerated in previously treated patients with advanced neuroblastoma.
在意大利的五家机构对晚期神经母细胞瘤患儿进行了一项II期试验，以评估拓扑替康联合长春新碱和多柔比星的抗肿瘤活性和耐受性。
年龄大于1岁的III期或IV期神经母细胞瘤患儿，均曾接受过化疗，且被诊断为难治性或复发性疾病，接受拓扑替康静脉注射治疗，剂量为1.5mg/m²（对于在先前大剂量化疗后1年内接受治疗的患者，剂量为0.75mg/m²），每日1次，共5天，随后静脉滴注2mg/m²长春新碱和45mg/m²多柔比星，持续48小时。治疗周期每3周重复一次。
25例患者（2例III期疾病，23例IV期疾病；19例难治性疾病，6例复发性疾病）共接受了115个周期的治疗。4例患者完全缓解，12例患者部分缓解，4例患者轻度缓解或病情稳定，5例患者肿瘤进展。总体缓解率（包括完全缓解和部分缓解）为64%（95%置信区间，43 - 82%）。在本报告发布时，15例患者存活，在首次接受该治疗疗程后的4 - 16个月（中位时间为9个月）内无疾病进展。毒性一般仅限于造血系统。仅1例患者观察到剂量限制性毒性（4级肝毒性）。没有因感染或毒性原因导致的死亡。
拓扑替康 - 长春新碱 - 多柔比星联合方案在先前接受治疗的晚期神经母细胞瘤患者中具有活性且耐受性良好。
