Department of Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada.
Cancer. 2012 Feb 15;118(4):1130-7. doi: 10.1002/cncr.26358. Epub 2011 Jul 14.
Patients aged >10 years with rhabdomyosarcoma have an inferior outcome compared with patients ages 1 to 9 years, which may be explained by toxicities (adverse events [AEs]) that result in chemotherapy dose reductions.
AEs observed during 1 of 3 randomized chemotherapy regimens (vincristine, dactinomycin, and cyclophosphamide [VAC]; vincristine, dactinomycin, and ifosfamide [VAI]; or vincristine, ifosfamide, and etoposide [VIE]) in the Fourth Intergroup Rhabdomyosarcoma Study were recorded. The incidence of toxicities by age and treatment regimen was determined. The odds of developing AEs in a particular age group (ages 5-9 years, 10-14 years, and 15-20 years) were compared with the odds in the control group of patients ages 1 to 4 years.
In total, 657 patients were eligible for analysis. The estimated 5-year event-free survival rates were 78%, 83%, 67%, and 58% for the groups ages 1 to 4 years, 5 to 9 years, 10 to 14 years, and 15 to 20 years, respectively. Patients ages 15 to 20 years experienced less neutropenia (odds ratio [OR], 0.43; P < .0001), thrombocytopenia (OR, 0.41; P < .0001), anemia (OR, 0.34; P < .0001), and infection (OR, 0.41; P < .0001) compared with younger patients, although they received similar amounts of chemotherapy. In contrast, peripheral nervous system toxicity was higher in adolescents aged >10 years (OR, 4.18; P < .0001). Females experienced more neutropenia (OR, 1.28; P = .05) and thrombocytopenia (OR, 1.26; P = .06) compared with males.
Adolescents who received treatment for rhabdomyosarcoma experienced significantly less hematologic toxicity and more peripheral nervous system toxicity compared with younger children despite receiving similar amounts of chemotherapy. Although outcomes were inferior in adolescents, it was unclear whether the differences in toxicity observed in the current study had an impact on outcome. The authors concluded that future studies examining the age-related and sex-related differences in pharmacokinetics of chemotherapy are necessary.
与 1 至 9 岁的患者相比，年龄大于 10 岁的横纹肌肉瘤患者的预后较差，这可能是由于化疗剂量减少导致的毒性（不良事件[AE]）所致。
记录了第 4 次横纹肌肉瘤研究中 3 种随机化疗方案（长春新碱、放线菌素 D 和环磷酰胺[VAC]；长春新碱、放线菌素 D 和异环磷酰胺[VAI]；或长春新碱、异环磷酰胺和依托泊苷[VIE]）期间观察到的 AE。按年龄和治疗方案确定毒性的发生率。与年龄在 1 至 4 岁的对照组相比，特定年龄组（5-9 岁、10-14 岁和 15-20 岁）发生 AE 的可能性。
共有 657 名患者符合分析条件。估计的 5 年无事件生存率分别为 1 至 4 岁组为 78%、5 至 9 岁组为 83%、10 至 14 岁组为 67%和 15 至 20 岁组为 58%。15 至 20 岁的患者经历的中性粒细胞减少症（比值比[OR]，0.43；P <.0001）、血小板减少症（OR，0.41；P <.0001）、贫血症（OR，0.34；P <.0001）和感染症（OR，0.41；P <.0001）少于年轻患者，尽管他们接受了相似的化疗剂量。相比之下，年龄大于 10 岁的青少年外周神经系统毒性更高（OR，4.18；P <.0001）。与男性相比，女性经历的中性粒细胞减少症（OR，1.28；P =.05）和血小板减少症（OR，1.26；P =.06）更多。
尽管接受横纹肌肉瘤治疗的青少年接受了相似剂量的化疗，但与年龄较小的儿童相比，他们经历的血液学毒性明显较少，而外周神经系统毒性较高。尽管青少年的预后较差，但尚不清楚当前研究中观察到的毒性差异是否对结果有影响。作者得出结论，需要进行研究化疗药代动力学的年龄和性别相关差异的未来研究。
