Concomitant administration of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide for high-risk sarcomas - The St. Jude Children's Research Hospital experience
Concomitant administration of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide for high-risk sarcomas - The St. Jude Children's Research Hospital experience
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DOI：
10.1002/cncr.21810
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发表时间：
2006-04-15
期刊：
影响因子：
6.2
通讯作者：
Pappo, AS
中科院分区：
文献类型：
--
作者：
Navid, F;Santana, VM;Pappo, AS
背景。强化化疗可以改善高危儿科肉瘤患者的预后。长春新碱、阿霉素、环磷酰胺、异环磷酰胺和依托泊苷对儿童肉瘤非常有效。作者研究了在规定的时间内同时使用这些药物的可行性。方法。在前瞻性高危肉瘤 (HIRISA) 11 期试验 HIRISA1 中，高危肉瘤儿科患者在第 9 周开始放疗和/或手术前接受了 3 个周期的强化长春新碱、异环磷酰胺、依托泊苷、环磷酰胺和阿霉素 (VACIE)，同时接受长春新碱、环磷酰胺和阿霉素治疗 （第 9 周）以及长春新碱和异环磷酰胺（第 12 周）。然后给予另外三个周期的 VACIE。前 11 名患者的血液学恢复延迟后，对方案进行了修改 (HIRISA2)，将局部控制治疗延迟至 5 个周期的 VACIE 后（将在 18 周内完成）。对方案有反应的患者有资格接受自体干细胞支持的清髓巩固治疗。结果。 24 名患者中，11 名（中位年龄为 1.4.9 岁）患有尤文肉瘤家族肿瘤，9 名患者患有横纹肌肉瘤，4 名患者患有不可切除的促纤维增生性小圆细胞肿瘤。接受 HIRISA2 治疗的 13 名患者中有 7 名在指定时间内完成治疗，但接受 HIRISA1 治疗的 11 名患者均未完成治疗。可逆的 4 级骨髓抑制是最常见的毒性。主要的非血液毒性作用是粘膜炎、营养障碍、低血压和周围神经病变。三名患者死于中毒。 5 年生存率和 5 年无事件生存率估计值均为 45.8% 11.2%。结论。实施 VACIE 等强化化疗方案的可行性部分取决于局部控制治疗的时机。该方案与显着的毒性相关。
BACKGROUND. intensified chemotherapy may improve the outcome of patients with high-risk pediatric sarcomas. Vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide are highly effective against pediatric sarcomas. The authors investigated the feasibility of administering these agents concomitantly within a defined period.METHODS. in the prospective high-risk sarcoma (HIRISA) Phase 11 trial HIRISA1, pediatric patients with high-risk sarcomas received 3 cycles of intensive vincristine, ifosfamide, etoposide, cyclophosphamide, and doxorubicin (VACIE) before radiotherapy and/or surgery began at Week 9 With Concurrent vincristine, cyclophosphamide, and doxorubicin (Week 9) and vincristine and ifosfamide (Week 12). Three additional cycles of VACIE were then given. After delayed hematologic recovery in the first 11 patients, the protocol was modified (HIRISA2) to delay local control therapy until after 5 cycles of VACIE (to be completed within 18 weeks). Patients who responded to the protocols were eligible for myeloablative consolidation with autologous stem cell support.RESULTS. Eleven of 24 patients (median age, 1.4.9 years) had Ewing sarcoma family Of tumors, 9 patients had rhabdomyosarcoma, and 4 patients had unresectable desmoplastic small round cell tumors. Seven of 13 patients on HIRISA2, but none of I I patients on HIRISA1, completed therapy within the specified time. Reversible Grade 4 myelosuppression was the most common toxicity. Major nonhematologic toxic effects were mucositis, nutritional impairment, hypotension, and peripheral neuropathy. Three patients died of toxicity. The 5-year survival and 5-year event-free Survival estimates both were 45.8% 11.2%.CONCLUSIONS. The feasibility of administering intensive chemotherapy regimens like VACIE was dependent in part on the timing of local control therapy. This regimen was associated with significant toxicity.