Division of Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
Biostatistics Shared Resource, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.
Oncologist. 2020 Feb;25(2):150-155. doi: 10.1634/theoncologist.2019-0532. Epub 2019 Oct 2.
Vincristine, doxorubicin, and cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE) administered every 2 weeks demonstrated a superior event-free survival compared with 3-week dosing in a landmark pediatric trial and is now standard of care for younger patients. Only 12% of patients enrolled in that trial were over 18 years of age; thus, the feasibility of interval-compressed VDC/IE in adults remains poorly described. We conducted a retrospective analysis of our institutional experience using this regimen.
Pharmacy administration records at Oregon Health and Science University were reviewed to identify patients with Ewing and Ewing-like sarcoma aged 18 years and older who received VDC/IE every 2 weeks.
We identified 24 patients. Median age was 28 years (range 18-60 years). At diagnosis, 67% had localized disease. The most common primary sites were extremity (38%) and pelvis (17%); another 25% had extraosseous disease. The median interval between cycles was 15.0 days, with no difference between patients aged <30 years versus ≥30 years. The median number of admissions for toxicity per patient was two, primarily for febrile neutropenia. Early treatment discontinuation occurred in 17%. Dose reductions were minimal, with mean cumulative doses achieved comparable to original planned dose and no difference between patients aged <30 years versus ≥30 years.
For adults with Ewing and Ewing-like sarcoma, administration of interval-compressed chemotherapy is feasible, without significant dose reductions required. Our results are comparable to prior studies involving a primarily pediatric population.
For Ewing sarcoma, interval-compressed vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide administered every 2 weeks rather than every 3 weeks has been shown to improve event-free survival in pediatric patients. However, in adults, oncologists may be hesitant to pursue interval-compressed therapy because of concerns for feasibility. In the adult population in this study, a median interval between cycles of 15.0 days (mean 17.0 days) was achieved, comparable to the interval achieved in AEWS0031 (median 15.0, mean 17.3 days). Given that this was achieved without unexpected toxicity or substantial dose reductions and that clinical outcomes were favorable compared with adult historical controls, these results support the use of this regimen in adults.
在一项具有里程碑意义的儿科试验中，与每 3 周给药相比，长春新碱、多柔比星和环磷酰胺（VDC）与异环磷酰胺和依托泊苷（IE）交替给药每 2 周给药一次，显示出更好的无事件生存。目前，该方案是年轻患者的标准治疗方法。该试验中只有 12%的患者年龄超过 18 岁；因此，成年人中间隔压缩 VDC/IE 的可行性描述较差。我们对使用该方案的机构经验进行了回顾性分析。
俄勒冈健康与科学大学的药房管理记录被审查，以确定年龄在 18 岁及以上患有尤因肉瘤和尤因样肉瘤的患者，他们每 2 周接受一次 VDC/IE。
我们确定了 24 名患者。中位年龄为 28 岁（范围 18-60 岁）。在诊断时，67%的患者为局限性疾病。最常见的原发部位为四肢（38%）和骨盆（17%）；另外 25%的患者有骨外疾病。周期之间的中位间隔为 15.0 天，年龄<30 岁与≥30 岁的患者之间无差异。每位患者因毒性住院的中位数为两次，主要是发热性中性粒细胞减少症。17%的患者早期停止治疗。剂量减少很小，累积剂量达到平均计划剂量，年龄<30 岁与≥30 岁的患者之间无差异。
对于患有尤因肉瘤和尤因样肉瘤的成年人，给予间隔压缩化疗是可行的，不需要进行重大剂量减少。我们的结果与主要涉及儿科人群的先前研究相似。
对于尤文肉瘤，每 2 周而非每 3 周交替给予长春新碱、多柔比星和环磷酰胺与异环磷酰胺和依托泊苷的间隔压缩化疗已被证明可改善儿科患者的无事件生存。然而，在成年人群中，由于对可行性的担忧，肿瘤学家可能不愿意采用间隔压缩治疗。在本研究的成年人群中，每 2 周的周期之间达到了 15.0 天的中位间隔（平均 17.0 天），与 AEWS0031 中达到的间隔相似（中位 15.0，平均 17.3 天）。鉴于这是在没有意外毒性或实质性剂量减少的情况下实现的，并且与成人历史对照相比临床结果良好，这些结果支持在成人中使用该方案。
