Altaf Sadaf, Enders Felicity, Lyden Elizabeth, Donaldson Sarah S, Rodeberg David, Arndt Carola
Departments of *Pediatric and Adolescent Medicine †Statistics and Informatics, Mayo Clinic, Rochester MN ‡Preventive and Societal Medicine, University of Nebraska Medical Center, Omaha, NE §Stanford University School of Medicine, Stanford, CA ∥Division of Pediatric Surgery, East Carolina University, Greenville, NC.
J Pediatr Hematol Oncol. 2014 Nov;36(8):599-604. doi: 10.1097/MPH.0000000000000192.
On the Fourth Intergroup Rhabdomyosarcoma study, older children experienced excessive neurotoxicity, whereas younger children had increased myelosuppression. The purpose of this study was to determine whether the same pattern of toxicity was seen on the successor study when use of growth factor was required and dosing of chemotherapy was different by performing a retrospective cohort analysis on patients treated on Children's Oncology Group protocol D9803. Toxicity data were analyzed by stratifying children into 4 age groups. The frequency of grade 3/4 neurotoxicity, myelosuppression, infection, and mucositis was predicted for each age group. The cumulative doses of vincristine and cyclophosphamide administered were measured as percent of protocol-prescribed dose. Adolescents (aged 15+) were more likely to experience neurotoxicity compared with younger patients (odds ratio, 3.6; P<0.0001). There was no difference in myelosuppression, infection, or mucositis. The mean percent protocol-prescribed doses administered for vincristine and cyclophosphamide did not differ much by age group. Adolescents experienced more neurotoxicity with vincristine compared with younger patients. No differences in other toxicities were observed between age groups. As adolescents received at least 85% of protocol-prescribed doses of vincristine, it is difficult to attribute the poorer survival in this age group to inadequate protocol-delivered therapy.
在第四项横纹肌肉瘤多中心研究中，年龄较大的儿童出现了过度的神经毒性，而年龄较小的儿童则出现了更严重的骨髓抑制。本研究的目的是通过对接受儿童肿瘤学组D9803方案治疗的患者进行回顾性队列分析，确定在后续研究中，当需要使用生长因子且化疗剂量不同时，是否会出现相同的毒性模式。通过将儿童分为4个年龄组来分析毒性数据。预测了每个年龄组3/4级神经毒性、骨髓抑制、感染和粘膜炎的发生率。测量了长春新碱和环磷酰胺的累积给药剂量占方案规定剂量的百分比。与较年轻的患者相比，青少年（15岁及以上）更易出现神经毒性（优势比为3.6；P<0.0001）。在骨髓抑制、感染或粘膜炎方面没有差异。长春新碱和环磷酰胺的平均给药剂量占方案规定剂量的百分比在各年龄组之间差异不大。与较年轻的患者相比，青少年使用长春新碱时神经毒性更大。各年龄组在其他毒性方面未观察到差异。由于青少年接受了至少85%方案规定剂量的长春新碱，因此很难将该年龄组较差的生存率归因于方案规定治疗不足。
